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Development of an optimal drug delivery system is a key factor within development process of a medicine. In concordance with increasing complexity of active pharmaceutical ingredients and medical treatments, advanced drug delivery systems are implemented, contributing to the increased efficiency and prolonged life cycle of medicines. At the Department of Pharmaceutical Technology the contemporary trends in development of innovative delivery systems are successfully followed and expertise based solutions are provided for the challenges arising within industrially established technologies. The present paper represents our most valuable research achievements in the last ten years: development of patient-friendly drug delivery systems, implementation of modern technologies in manufacturing medicines by quality by design, technological approaches for improving solubility and bioavailability of active pharmaceutical ingredients, mukoaddevelopment of stable biopharmaceutics and nanocarriers, all for the purpose of more effective therapy. Razvoj optimalnega dostavnega sistema je pomemben dejavnik v celotnem procesu razvoja zdravila. Z naraščajočo kompleksnostjo novih zdravilnih učinkovin in postopkov zdravljenja postajajo tudi dostavni sistemi vse naprednejši, kar prispeva k večji učinkovitosti in podaljšanju življenjskega cikla zdravil. Na Katedri za farmacevtsko tehnologijo uspešno sledimo sodobnim trendom razvoja inovativnih dostavnih sistemov, z našo ekspertizo pa se učinkovito vključujemo tudi v reševanje perečih izzivov industrijsko že uveljavljenih tehnologij. V članku predstavljamo naše najpomembnejše raziskovalne dosežke predvsem v zadnjih desetih letih: razvoj bolnikom prijaznih dostavnih sistemov, uporaba sodobnih tehnologij za izdelavo zdravil z vgrajeno kakovostjo, pristopi za povečanje topnosti in biološke uporabnosti, razvoj stabilnih biofarmacevtikov ter nanodostavnih sistemov, vse z namenom učinkovitejšega zdravljenja.

Nowadays, cosmetology and cosmetic products are one of the fastest-growing scientific areas, increasingly focused towards individuals' needs and preferences. Thus, we are facing with new trends that include cosmetic products with added value plus a zero-waste mentality which is changing current consumers' habits. Cosmetic products based on biological macromolecules, including peptides, can indisputably be enclosed within this field, representing the scope of this article. In the following review, new trends in the field of cosmetic products with incorporated peptides as cosmetically active ingredients are pointed out. moreover, benefits as well as challenges in terms of development and efficiency of such products are critically depicted. Throughout the contribution, authors want to answer the question regarding relevance of using peptides in the active care as well as their effects on the skin surface. Kozmetologija je dandanes ena najhitreje razvijajočih se znanstvenih področij. Posledično postaja razvoj kozmetičnih izdelkov vedno bolj inovativen ter usmerjen k posamezniku in njegovim potrebam oz. željam. Tako se soočamo z novimi trendi, ki vključujejo kozmetične izdelke z dodano vrednostjo, ter skladno z miselnostjo o industriji >>brez odpadkov<< (zero-waste) spreminjajo dosedanje nakupovalne navade potrošnikov. V ta pristop nedvoumno sodijo kozmetični izdelki na osnovi bioloških makromolekul, vključno s peptidi. V prispevku so predstavljene prednosti peptidov kot kozmetično aktivnih sestavin, hkrati z izzivi, ki jih predstavljata razvoj in vrednotenje učinkovitosti tovrstnih izdelkov. Skozi prispevek želimo odgovoriti na vprašanje o smotrnosti uporabe peptidov v aktivni negi, torej o delovanju v globljih plasteh kože, ter hkrati pojasniti njihove učinke na površini kože.

The assessment of dermal absorption of molecules is one of the main steps in the initial design and later in the evaluation of dermal or transdermal drug delivery systems. Laboratory test systems require a membrane to mimic the barrier function of stratum corneum. The following membranes are discussed: synthetic membranes, animal models, human skin and reconstructed human epidermis. In vitro testiranja dermalne absorpcije zdravilnih učinkovin so pomemben del razvoja in vrednotenja dermalnih oz. transdermalnih dostavnih sistemov. Za določanje dermalne absorpcije in vitro nujno potrebujemo ustrezno membrano, ki v zadostni meri oponaša barierne lastnosti rožene plasti. V članku so predstavljene različne membrane, ki se uporabljajo: umetne membrane, živalska ter človeška koža in rekonstruirani celični kožni modeli.

Transepidermalna izguba vode je poglavitni dejavnik stanja kože, ki nam pomaga pri vrednotenju barierne funkcije kože. Skrbna nega kože s pravilno izbranimi kozmetičnimi izdelki je ključna za vzdrževanje optimalne ravni vlage in s tem posredno njene zaščitne vloge. V ta namen pogosto uporabljamo hidrogele, nosilne sisteme s širokim spektrom uporabe, ki imajo na področju medicine, farmacije, biotehnologije in kozmetologije pomembno vlogo. V okviru diplomskega dela smo na prašičji koži in vitro vrednotili dva sklopa hidrogelov, in sicer hidrogele, ki temeljijo na nanokristalni celulozi, vrsti nanomateriala, pridobljenega iz celuloze, ter hidrogele za čiščenje obraza s sirotko, stranskim produktom pri proizvodnji sira. Zanimal nas je njihov vpliv na barierno funkcijo kože, natančneje na transepidermalno izgubo vode (TEWL). Prvi sklop hidrogelov na osnovi nanokristalne celuloze so predstavljale štiri formulacije hidrogelov z različno kvalitativno in kvantitativno sestavo, in sicer naravni polimer (aginat ali pektin), variabilni delež vode in eno od dveh vrst nanokristalne celuloze. Med vrednotenjem smo opazili, da so končne vrednosti TEWL vseh štirih formulacij primerljive in iz dobljenih rezultatov ni mogoče nedvoumno potrditi pozitivnih učinkov uporabe hidrogela na zmanjšanje vrednosti TEWL. V nadaljevanju smo omenjene hidrogele posušili do nastanka filmov in preučili tudi vpliv slednjih na vrednosti TEWL. S pridobljenimi rezultati smo potrdili, da je uporaba filmov na koži koristna, kar potrjujejo tudi vrednosti TEWL, ki so pri vseh paralelah ostale primerljive z bazalnimi vrednostmi. V nadaljevanju naloge smo se osredotočili na formulacije hidrogelov za čiščenje obraza s sirotko, razvite v okviru predhodnih raziskav. Želeli smo ovrednotiti njihov potencial draženja, glede na različno koncentracijo vgrajene površinsko aktivne snovi. Ugotovili smo, da vgrajena površinsko aktivna snov ni izkazala negativnega vpliva na barierno funkcijo kože tako so razviti hidrogeli za čiščenje obraza primerni za uporabo tudi na bolj občutljivi koži. Z rezultati diplomske naloge smo potrdili pomembnost vrednotenja hidrogelov in vitro pred njihovo uporabo na koži. Rezultati vrednotenja TEWL so zato bistveni pri razvoju vlažilnih in nedražečih hidrogelov za nanos na kožo. Transepidermal water loss is one of the main properties of the skin indicative of its barrier function. Careful skin care with properly selected cosmetic products is crucial for maintaining an optimal level of moisture in the skin and, to maintain its protective role. Hydrogels, carrier systems with a wide range of applications, are often used for this purpose and play an important role in the fields of medicine, pharmacy, biotechnology and cosmetology. As part of the thesis work, two sets of hydrogels were evaluated on porcine skin in vitro. The first set consisted of hydrogels based on nanocrystalline cellulose, a type of nanomaterial derived from cellulose, and the second set consisted of hydrogels for facial cleansing with whey, a by-product of cheese production. We were interested in their impact on the skin's barrier function, specifically on transepidermal water loss. The first set of hydrogels based on nanocrystalline cellulose consisted of four formulations with different qualitative and quantitative compositions, namely, a natural polymer (aginate or pectin), a variable proportion of water and one of two types of nanocrystalline cellulose. During the evaluation, we observed that the final TEWL values of all four formulations were comparable, and the obtained results did not unequivocally confirm the positive effects of hydrogel application in reducing TEWL values. In addition, we also dried these hydrogels to form films and examined their influence on TEWL values. With the obtained results, we confirmed that the use of films is beneficial, which is further supported by TEWL values that remained comparable to the basal values for all parallels. In the continuation of the study, we focused on facial cleansing formulations with whey, developed in previous studies. We wanted to evaluate their potential for irritation based on the different concentration of the incorporated surfactant. We found that the incorporated surfactant did not have a negative impact on the skin's barrier function. Therefore, the developed hydrogels for facial cleansing are suitable for the use on even more sensitive skin. With the results of this thesis, we confirmed the importance of in vitro evaluation of hydrogels before their application on the skin. The results of the TEWL evaluation are therefore essential for the development of moisturizing and non-irritating hydrogels for skin application.

Pomen zdravil za subkutano aplikacijo je čedalje večji, predvsem zaradi številnih prednosti, ki jih ta način apliciranja zdravil ponuja, tako za bolnika kot zdravstveni sistem. S pomočjo elektronskih podatkovnih baz PubMed in ScienceDirect smo proučevali področje subkutane aplikacije z vidika vgrajenih zdravilnih učinkovin in tehnoloških specifik pri oblikovanju formulacij za subkutano dostavo. Pregled smo naredili po različnih časovnih obdobjih, in sicer od 2013 do 2017 in od 2018 do 01/2023. Razvidno je bilo povečevanje števila objav v zadnjem obdobju, prednjačijo pa raziskovalni članki, skupno 153, napram 45 preglednim člankom. Na področju subkutane aplikacije je glavnina raziskovanja vezana na zdravilne učinkovine, ki so ali bi bile primerne za subkutani način apliciranja, predvsem učinkovine biološkega izvora za zdravljenje avtoimunih bolezni (npr. luskavica, revmatoidni artritis). Aktualno je tudi področje različnih tehnologij izdelave in uporabe novih inovativnih pomožnih snovi (npr. rekombinantna humana hialuronidaza) v formulacijah. S pomočjo Centralne baze zdravil smo naredili izbor vseh zdravil za subkutano aplikacijo, ki imajo trenutno veljavno dovoljenje za promet z zdravilom, ne glede na to ali so na voljo na trgu ali imajo priglašeno motnjo v oskrbi ali potekajoče začasno prenehanje (trenutno jih je na voljo 221). Ugotovili smo, da je večina zdravil za subkutano aplikacijo v Sloveniji v obliki raztopine za injiciranje. Na trgu izstopa skupina insulinov, sledijo ji različne učinkovine biološkega izvora. V Sloveniji trenutno prevladujejo originatorji, vendar je razlika v primerjavi z generiki skoraj zanemarljiva. S pomočjo povzetka glavnih značilnosti zdravil, ki se nahaja na Centralni bazi zdravil smo naredili povzetek vseh pomožnih snovi, ki se uporabljajo v zdravilih za subkutano aplikacijo, ki so trenutno na voljo na slovenskem trgu. Ugotovili smo, da lahko uporabljene pomožne snovi razdelimo v več skupin po njihovi vlogi v formulaciji (npr. pufri, adjuvansi, solubilizatorji, snovi za uravnavanje osmolarnosti). Je pa uporaba posameznih skupin pomožnih snovi v tesni povezavi s farmacevtsko obliko, v kateri se nahaja zdravilo za subkutano aplikacijo. The importance of subcutaneous administration is growing, for the most part due to many advantages this route of drug administration offers both for the patient and the healthcare system in general. Using the online databases PubMed and ScienceDirect, we investigated the field of subcutaneous administration with regard to active ingredients and technological approaches in the design of formulations for subcutaneous delivery, over different time periods, namely from 2013 to 2017 and from 2018 to 01/2023. The number of articles increased with each period, with research articles being the most prominent, with a total of 153 articles compared to 45 review articles. In the field of subcutaneous administration, the main focus of research is on active substances that are or could be suitable for subcutaneous administration, in particular active substances of biological origin for the treatment of autoimmune diseases (e.g. psoriasis, rheumatoid arthritis). Researchers are also focusing on the investigation of different technologies for the production and use of new innovative excipients (e.g. recombinant human hyaluronidase) in formulations. Using the Central Medicines Database, we have made a selection of all subcutaneous medicinal products with a currently valid marketing authorisation, whether they are available on the market or have a notified supply disruption or an ongoing suspension (currently 221). We have found that the majority of subcutaneous medicinal products in Slovenia are in the form of an injectable solution. The insulin group stands out on the market, followed by various active substances of biological origin. Originators currently dominate in Slovenia, but the difference is almost negligible compared to generics. Using the summary of the main characteristics of medicinal products available on the Central Medicines Database, we have summarised all excipients used in subcutaneous injectable medicinal products currently available on the Slovenian market. We found that the excipients used can be divided into several groups according to their role in the formulation (e.g. buffers, adjuvants, solubilisers, osmolarity adjusters). However, the use of each group of excipients is closely related to the pharmaceutical form of medicinal product for subcutaneous delivery.

Proteine in peptide uvrščamo v pomembno skupino kozmetično aktivnih sestavin. Njihovi učinki na kožo so raznoliki, od vlaženja, protimikrobne zaščite, hkrati pa posnemajo delovanje naravno prisotnih proteinov kože, zlasti kolagena in elastina. Ena izmed surovin s pomembno vsebnostjo proteinov je tudi sirotka, ki je dolgo veljala za odpadek, ki nastane kot stranski produkt pri predelavi mleka v sir, danes pa se s pridom izkorišča v različnih industrijskih panogah. V kozmetičnih formulacijah, najpogosteje v šamponih, balzamih, čistilnih losjonih in gelih, se uporablja za stabilizacijo emulzij in pen, tvorbo filmov, za vezavo vode in kot tvorilec gela. Sirotko velja izpostaviti kot vir kozmetično aktivnih sestavin za nego kože in las oz. lasišča zaradi bogate vsebnosti proteinov, kot so β-laktoglobulin, α-laktalbumin, imunoglobulin ter številnih drugih skupin. V diplomski nalogi smo razvili in optimizirali dve kozmetični formulaciji z vgrajeno sirotko, in sicer hidrogela za čiščenje obraza, ki sta se razlikovala glede na vrsto uporabljenega zgoščevala, tj. ksantan oz. karbomer. V začetni fazi razvoja smo določili optimalni koncentraciji ksantana in karbomera ter temu prilagodili ustrezno količino decil glukozida, ki deluje kot površinsko aktivna snov. V naslednji fazi je sledilo določanje ustreznega deleža sirotke, in sicer smo želeli vgraditi čim večjo količino le te, brez neugodnega vpliva na fizikalno-kemijske in organoleptične lastnosti formulacij. V zadnjem delu naloge smo tri izbrane formulacije hidrogelov (30 % sirotke, 1,5 % ksantana, 10 % decil glukozida 15 % sirotke, 1 % karbomera, 10 % decil glukozida in 30 % sirotke, 1 % karbomera, 10 % decil glukozida), ki so ustrezale kriterijem organoleptičnih lastnosti, viskoznosti ter pH vrednosti, izpostavili stabilnostni študiji, ta je vključevala testiranje vzorcev shranjenih na sobni temperaturi (25 °C) ter na povišani temperaturi (40 °C). V vnaprej določenih časovnih točkah smo testiranim vzorcem vrednotili viskoznost, pH in organoleptične lastnosti. V okviru 42-dnevne stabilnostne študije smo ugotovili, da ima sirotka največji vpliv na organoleptične lastnosti izdelkov, tj. na spremembo barve in vonja. Zaključimo lahko, da so vsi trije vzorci s sirotko kemijsko (pH, organoleptične lastnosti) stabilni, ne glede na vrsto polimera kot zgoščevala. Rezultate bi bilo smiselno nadgraditi v okviru dolgoročnih stabilnostnih študij, predstavljajo pa dobro izhodišče za razvoj kakovostnih kozmetičnih izdelkov na osnovi sirotke. Proteins and peptides are an important group of cosmetically active ingredients. Their effects on the skin are diverse, ranging from moisturising, antimicrobial protection and mimicking the action of naturally occurring skin proteins, in particular collagen and elastin. One of the raw materials with an important protein content is whey, which was long considered to be a waste by-product of the processing of milk into cheese, but is nowadays used to great advantage in various industries. In cosmetic formulations, most commonly in shampoos, conditioners, cleansing lotions and gels, it is used to stabilise emulsions and foams, to form films, to bind water and as a gel-forming agent. Whey should be highlighted as a source of cosmetically active ingredients for skin and hair or scalp care due to its rich content of proteins such as β-lactoglobulin, α-lactalbumin, immunoglobulin and many others. In the diploma thesis, we developed and optimised two cosmetic formulations with incorporated whey, namely hydrogels for facial cleansing, which differed according to the type of thickener used, i.e. xanthan or carbomer. In the initial phase of development, the optimum concentrations of xanthan and carbomer were determined and the corresponding amount of decyl glucoside, which acts as a surfactant, was adjusted accordingly. The next stage was to determine the appropriate proportion of whey, with the aim of incorporating as much whey as possible without adversely affecting the physico-chemical and organoleptic properties of the formulations. In the last part of the task, three selected hydrogel formulations (30 % whey, 1,5 % xanthan, 10 % decyl glucoside) were prepared 15 % whey, 1 % carbomer, 10 % decyl glucoside and 30 % whey, 1 % carbomer, 10 % decyl glucoside), which met the criteria of organoleptic properties, viscosity and pH value, were subjected to a stability study, which involved testing samples stored at room temperature (25 °C) and at elevated temperature (40 °C). At predetermined time points, the viscosity, pH and organoleptic properties of the tested samples were evaluated. In the 42-day stability study, whey was found to have the greatest influence on the organoleptic properties of the products, i.e. colour and odour changes. It can be concluded that all three samples with whey are chemically stable (pH, organoleptic properties), irrespective of the type of polymer as thickener. The results should be further developed in the context of long-term stability studies and represent a good starting point for the development of quality cosmetic products based on whey.

Za aktivno nego (foto) starane kože v kozmetiki pogosto uporabljamo kozmetično aktivne sestavine, ki vplivajo na strukturo kože in njene biološke funkcije. Pomembno skupino predstavljajo proteini in peptidi, med katere uvrščamo tudi sirotko. Sirotka je namreč tekoči vir proteinov, ki nastane s proizvodnjo sira. V preteklosti je veljala za industrijsko onesnaževalo, danes pa je uveljavljena sestavina, ki se zaradi ugodnih učinkov in vpliva na lastnosti same formulacije vgrajuje v kozmetične izdelke za nego kože in las. Sirotka je lahko v suhi ali tekoči obliki, z membransko filtracijo pa dobimo sirotko različne čistosti – prah, koncentrat, izolat, hidrolizat in permeat. V diplomski nalogi smo vrednotili tri najbolj optimalne formulacije šamponov z in brez vgrajene tekoče sirotke, razvite v okviru predhodnih raziskav na Katedri za farmacevtsko tehnologijo na Fakulteti za farmacijo. Želeli smo ovrednotiti potencial draženja po nanosu šamponov z različno sestavo. Šampon je kozmetični izdelek za lase, namenjen čiščenju in odstranjevanju umazanije z las in lasišča, posledično vsebuje visoko koncentracijo površinsko aktivnih snovi, ki so potencialno dražeče. V nadaljevanju smo zato pripravili tudi raztopine površinsko aktivnih snovi v različnih koncentracijah in razmerjih, kar nam je pomagalo pri interpretaciji dobljenih vrednosti za končne formulacije. Zanimalo nas je, kako šamponi in raztopine vplivajo na transepidermalno izgubo vode, to je pasivna izguba vode skozi intaktno roženo plast. Poskus smo izvedli na modelu prašičje kože in vitro, ki smo jo vpeli v Franzovo difuzijsko celico. V okviru preliminarnega testiranja smo določili optimalno časovno točko za meritev transepidermalne izgube vode po odstranitvi formulacije. Odločili smo se, da bomo bazalne vrednosti primerjali s končnimi vrednostmi po desetih in dvajsetih minutah od odstranitve formulacij in raztopin. S Tewametrom®TM 300 smo izmerili bazalno vrednost pred nanosom formulacije in vrednost transepidermalne izgube vode po njeni odstranitvi. Snov se opredeli kot dražečo, če je razlika med bazalno in končno vrednostjo večja ali enaka 6 g/m²/h. Ugotovili smo, da formulacije šamponov s 15 % vsebnostjo natrijevega lavrilsulfata dražijo kožo. Prav tako so rezultati potrdili, da je kokamid dietanolamid problematična, dražeča spojina, zato se naj v kozmetične izdelke vgrajuje v čim manjši koncentraciji. For the active care of (photo) aged skin, cosmetically active ingredients that affect the structure of the skin and its biological functions are often used in cosmetics. One such ingredients are proteins and peptides, including whey. Whey is a liquid source of proteins produced by cheese production. In the past it was considered an industrial pollutant, but today it is a well-established ingredient that is incorporated into cosmetic products for skin and hair care due to its beneficial effects on skin and hair as well as on formulation’ features. Whey can be in dry or liquid form and membrane filtration produces whey of different purities - powder, concentrate, isolate, hydrolysate and permeate. In this thesis, we evaluated the three most optimal shampoo formulations with and without incorporated liquid whey, developed in the framework of previous research at the Department of Pharmaceutical Technology, Faculty of Pharmacy. The aim was to evaluate the potential irritation after application of shampoos with different composition. Shampoo is a cosmetic hair product designed to clean and remove dirt from the hair and scalp, therefore it contains a high concentration of surfactants, which can irritate the skin. Therefore we have also prepared surfactants solutions in different concentrations and ratios to help us interpret the values obtained for the final formulations. We were interested in how these shampoos and solutions affect transepidermal water loss, i.e. the passive loss of water through the intact stratum corneum. The experiment was carried out ion a pig skin model embedded in a Franz diffusion cell in vitro. As part of preliminary testing, the optimal time points for measuring transepidermal water loss after formulation removal were determined. We decided to compare the baseline values with the final values at ten and twenty minutes after removal of the formulations or surfactant solutions. The basal value before the application of the formulation and the transepidermal water loss value after its removal were measured using a Tewameter®TM 300. A substance is defined as an irritant if the difference between the basal and final value is equal or higher than 6 g/m²/h. All shampoo formulations containing 15 % sodium lauryl sulphate were found to be skin irritants. The results also confirmed that cocamide diethanolamide is a problematic, irritant compound and should therefore be incorporated in cosmetic products at the lowest possible concentration.

Koža moških in žensk se razlikuje v številnih morfoloških in fizioloških lastnostih, ki se nanašajo na njeno debelino, poraščenost in kisel hidro-lipofilni plašč na površini kože. Zaradi omenjenih lastnosti je potrebno kožo moških negovati, zaščititi in čistiti s kozmetičnimi izdelki, zasnovanimi posebej za moške. V osnovi moški uporabljajo širok spekter kozmetičnih izdelkov, in sicer izdelke za britje, osebno higieno in nego kože, za nego las ter parfume. V prvem delu diplomske naloge smo proučevali kozmetične izdelke za moške in izvedli primerjavo s kozmetičnimi izdelki za ženske. Najprej smo se osredotočili na kozmetične izdelke za britje, namreč britje velja za moško vsakodnevno rutino, in sicer smo analizirali sestavo krem in pen za britje ter vodic po britju. Zanimale so nas sestavine, ki se najpogosteje pojavljajo v izdelku in njihova vloga. Prav tako smo podrobneje proučili vlogo in delovanje tistih sestavin, ki se nahajajo v vsaj dveh pregledanih izdelkih. Rezultati kažejo, da imajo kreme in pene za britje podobno sestavo, namreč oba tipa izdelkov vsebujeta podobne osnovne sestavine, največja razlika med proučevanima tipoma izdelkov je uporaba potisnih plinov v penah za britje. Vodice po britju vsebujejo večji del vodne faze, konzervansov in dišav, kot že omenjena tipa izdelkov za britje. V nadaljevanju smo proučili razlike in podobnosti v formulaciji med izbranimi izdelki, ki jih uporabljajo tako moški kot ženske. V nabor proučevanih izdelkov smo vključili vlažilne kreme, gele za prhanje in antiperspirante za moške ter odgovarjajoče število vlažilnih krem, gelov za prhanje in antiperspiranov za ženske istega proizvajalca. Ugotovili smo, da se izdelki za moške in ženske razlikujejo v ceni, številu sestavin in v posameznih uporabljenih pomožnih sestavinah in kozmetično aktivnih sestavinah. V drugem sklopu naloge smo z anketnim raziskovanjem med prostovoljci moškega spola proučevali njihove navade in preference pri nakupu in uporabi kozmetičnih izdelkov. Anketo je popolno izpolnilo 40 anketirancev, rezultati pa so pokazali, da jih četrtina neredno uporablja kozmetične izdelke. Večina odšteje do 15 € mesečno za nakup kozmetike in uporablja od tri do pet izdelkov v svoji dnevni rutini, najpomembnejši dejavnik pri nakupu kozmetike je razmerje med ceno in kakovostjo in v večini so anketiranci zadovoljni s ponudbo kozmetike za moške. Vpogled v njihove potrošniške navade pa smo dobili v sklopu anketiranja zaposlenih v treh enotah Javnega zavoda Lekarne Ljubljana z vprašalnikom odprtega tipa. Ugotovili smo, da moški redko obiščejo lekarno z namenom nakupa kozmetike, najpogosteje kupijo en izdelek za katerega odštejejo med 15 in 25 €, najpomembnejši dejavnik pri nakupu pa predstavlja svetovanje zaposlenih. Na osnovi ugotovitev, pridobljenih v okviru diplomske naloge, lahko zaključimo, da so kozmetični izdelki za moške v večini ustrezno formulirani in prilagojeni specifičnim morfološkim in fiziološkim lastnostim moške kože ter da se odnos moških do kozmetike pospešeno razvija. The skin of men and women differs in many morphological and physiological characteristics related to its thickness, facial and body hair and protective hydrolipid acid film on the skin surface. Therefore it is necessary to use cosmetic products designed specifically for men for care, protection and cleansing of men's skin. Men use a wide range of cosmetic products, namely shaving products, hair care products, personal hygiene, skin care products, and perfumes. In the first part of the thesis, we studied cosmetic products for men and performed a comparison study to cosmetic products for women. Firstly, we focused on cosmetic products for shaving, as shaving is considered a man's daily routine, therefore we analyzed the composition of shaving creams, shaving foams and aftershave waters. We were interested in the ingredients that appear most often in the product and their role. We also studied in more detail the role and function of those ingredients that are found in at least two of the studied products. Our results show that shaving creams and shaving foams are similar in composition, namely both types of products contain similar basic ingredients, the biggest difference between the studied types of products is the use of propellant gases in shaving foams. Aftershaves contain more water phase, preservatives and fragrances than the aforementioned types of shaving products. In the following, we examined the differences and similarities in the formulation between selected products used by both men and women. In the set of studied products, we included moisturizing creams, shower gels and antiperspirants for men and the corresponding number of moisturizing creams, shower gels and antiperspirants for women from the same manufacturer. We found that the products for men and women differ in price, number of ingredients and in the individual excipents and cosmetically active ingredients used. In the second part of the task, we studied the habits and preferences of male volunteers for purchase and usage of cosmetic products through survey research. The survey was fully completed by 40 respondents, and the results showed that a quarter of them use cosmetic products irregularly, most of them spend up to 15 € a month to buy cosmetics and use three to five products in their daily routine, the most important factor for purchase being the price to quality ratio, and most of the respondents are satisfied with cosmetics for men on the market. We gained an insight into their consumer habits as part of a survey of employees in three units of the Public Institute of the Ljubljana Pharmacy with an open-ended questionnaire. We found that men rarely visit a pharmacy with the intention of buying cosmetics, in most cases they buy one product for which they deduct between 15 and 25 €, and the most important factor in the purchase is the advice by the employees. Based on the findings obtained in our thesis, we can conclude that cosmetic products for men are in most cases properly formulated and adapted to the specific morphological and physiological characteristics of male skin, and that men's attitude towards cosmetics is developing rapidly.

Atopijski dermatitis (AD) je najpogostejša nenalezljiva kronična vnetna bolezen kože. Poleg pravilne/ustrezne in redne nege atopijske kože je zelo pomembna tudi lokalna terapija s protivnetnimi zdravilnimi učinkovinami (ZU). Dostavni sistemi z lamelarno strukturo bi, zaradi svoje podobnosti z medceličnimi lipidi rožene plasti lahko predstavljali ugodno podporno terapijo za bolnike z AD in omogočili podaljšano sproščanje protivnetnih ZU, kot je betametazondipropionat (BDP). V okviru magistrske naloge smo proučevali osem sistemov lamelarnih tekočih kristalov (TK) z različno kvali- in kvantitativno sestavo na osnovi konopljinega ali lanenega olja z vgrajenim BDP, in sicer smo izvedi stabilnostno študijo, sproščanje in vitro ter vrednotenje mikrostrukture. V okviru 10-tedenske pospešene stabilnostne študije smo ugotovili, da je stabilnost vgrajenega BDP odvisna predvsem od deleža vode v posameznih formulacijah. Stabilnost BDP je bila najboljša v formulacijah z 30 % deležem vodne faze, najslabša pa v formulacijah z 80 % deležem vodne faze. Izbira emulgatorja je v manjši meri vplivala na stabilnost BDP, ta je bila nekoliko manjša v vzorcih z Montanov 68 v primerjavi z vzorci s Tween 80. Kinetika razgradnje BDP v lamelarnih TK sledi 1. redu. Z metodo ozkokotnega rentgenskega sipanja smo vrednotili mikrostrukturo vzorcev in potrdili prisotnost lamelarnih mezofaz v vseh vzorcih ter tudi micelarne strukture v sistemih z večjim deležem vode in Montanov 68. Z večanjem deleža vodne faze v vzorcih se je povečevala razdalja med lamelami vzorcev. Mikrostrukturo smo ovrednotili pri različnih temperaturah, pomembnih za dermalno dostavo, tj. 25 °C (sobna temperatura), 32 °C (temperatura površine kože) in 37 °C (telesna temperatura). Temperatura ni imela značilnega vpliva na mikrostrukturo vzorcev, kar pomeni, da se ta ohrani tudi po nanosu formulacije na kožo. Prav tako vgradnja BDP ni vplivala na mikrostrukturo TK. V sklopu sproščanja in vitro, ki smo ga izvedli s pomočjo Franz-ovih difuzijskih celic in Strat-M® membran, smo potrdili podaljšano sproščanje BDP iz vseh osmih formulacij. Na sproščanje BDP je bistveno vplivala mikrostruktura posameznih vzorcev. Iz formulacij z lamelarnimi mezofazami in miceli je bilo sproščanje BDP v 24 h hitrejše in večje ((L/M)Lo80, (L/M)Ko80) kot v ostalih vzorcih. Sproščanje BDP iz formulacij smo primerjali z Beloderm® kremo (vsebnost BDP je enaka kot v TK in znaša 0,64 mg/g formulacije) in potrdili večji obseg sproščanja BDP iz vzorcev TK. Atopic dermatitis (AD) is the most common non-infectious chronic inflammatory skin disease. In addition to suitable and regular care of atopic skin, local therapy with anti-inflammatory drugs is of crucial importance. Due to their similarity to the intercellular lipids of the stratum corneum, delivery systems with lamellar structure could provide a favourable supportive therapy for patients with AD in addition to prolonged release of anti-inflammatory drugs such as betamethasone dipropionate (BDP). Within the scope of this Master's thesis, eight lamellar liquid crystal (LC) systems with different qualitative and quantitative composition based on hemp or flaxseed oil with incorporated BDP was studied, namely a stability study, in vitro release study and microstructure evaluation were performed. As observed within the 10-week accelerated stability study the stability of incorporated BDP depends mainly on the water content in individual formulations. BDP stability was the highest in samples with 30 % aqueous phase and the lowest in formulations with 80% aqueous phase. The choice of emulsifier has a minor effect on the stability of BDP, which was slightly lower in the samples with Montanov 68 compared to the samples with Tween 80. The BDP degradation in lamellar LC systems follows the 1st order kinetics. The microstructure of the samples was evaluated by the small angle X-ray scattering analysis with confirmed lamellar mesophases in all samples in addition to micellar structures in systems with higher water content and Montanov 68. The microstructure was evaluated at different temperatures relevant for dermal delivery, i.e. 25 ° C (room temperature), 32 ° C (skin temperature) and 37 ° C (body temperature). The temperature did not have a significant effect on the microstructure of the samples being preserved following skin application. Also, the incorporation of BDP did not affect the LC systems’ microstructure. Prolonged BDP release from all eight systems tested was observed within in vitro release study using Franz diffusion cells and Strat-M® membranes. The BDP release was significantly influenced by the microstructure of individual samples. From formulations with lamellar mesophases and micelles, the release of BDP was faster and higher ((L / M) Lo80, (L / M) Ko80) after 24h compared to other systems. BDP release from LC systems was compared to Beloderm® cream (with same BDP content, i.e. 0,64 mg/g of formulation) and higher release was observed for the LC systems.

Atopijski dermatitis je kronična, nenalezljiva vnetna bolezen kože, ki jo spremljajo srbečica in ponavljajoče ekcematozne lezije. Za bolnike je pomembna redna in pravilna nega kože, ključnega pomena pa je ustrezno zdravljenje, usmerjeno v obvladovanje in preprečevanje vnetja in srbenja. Prvo izbiro v okviru lokalnega zdravljenja atopijskega dermatitisa predstavljajo lokalni kortikosteroidi, vgrajeni v klasične farmacevtske oblike kot so kreme in mazila. Z raziskovalnim delom smo želeli doprinesti k izboljšanemu zdravljenju atopijskega dermatitisa z vgradnjo betametazondipropionata v sodobne dostavne sisteme, in sicer liotropne tekoče kristale. Slednji so izredno ugodni za dermalen nanos zaradi svoje specifične mikrostrukture. Obenem je bil ključnega pomena tudi izbor pomožnih snovi, pri čemer smo kot oljno fazo izbrali laneno ali konopljino olje zaradi visoke vsebnosti esencialnih maščobnih kislin s protivnetnim delovanjem, kar je ugodno za atopično kožo, emulgatorska faza je bila sestavljena iz biokompatibilnih površinsko aktivnih snovi, ki spodbujajo nastanek liotropnih tekočih kristalov, in sicer iz lecitina v kombinaciji s Tween 80 ali Montanov 68, hidrofilno fazo pa je predstavljala voda. V okviru eksperimentalnega dela smo z izdelavo (psevdo)trikomponentnih diagramov na podlagi organoleptičnih lastnosti opredelili področja nastanka tekočih kristalov za štiri različne kombinacije oljne faze in zmesi površinsko aktivnih snovi. Za nadaljnje vrednotenje smo izbrali vzorce na razredčitveni premici (tj. pri različnih deležih vode) s konstantnim razmerjem površinsko aktivnih snovi in olja 6/4 in jih z in brez vgrajenega betametazondiproprionata ovrednotili s polarizacijsko mikroskopijo. Za vzorce s Tween 80 smo po celotni razredčitveni premici potrdili nastanek lamelarnih tekočih kristalov, medtem ko smo pri Montanov 68 nastanek lamelarnih mezofaz potrdili zgolj pri določenih vzorcih v odvisnosti od deleža vodne faze. Oljna faza in tudi vgradnja zdravilne učinkovine ni vplivala na nastanek lamelarnih tekočih kristalov. V okviru nadaljnje reološke analize pa smo ugotovili, da se vgradnja zdravilne učinkovine odraža v spremenjenih vrednosti viskoznosti in dinamičnih modulov v primeru vzorcev s Tween 80, v vzorcih z Montanov 68 pa ni prišlo do bistvenih sprememb. Vrednotenje mikrostrukture smo izvedli pri sobni temperaturi (25 °C), pri temperaturi kože (32 °C) in telesni temperaturi (37 °C), pri čemer smo s polarizacijsko mikroskopijo potrdili, da se mikrostruktura ohranja tudi pri višjih temperaturah, medtem ko smo v primeru določenih vzorcev zaznali temperaturno odvisne spremembe viskoznosti. Zaključili smo, da so novo razviti liotropni tekoči kristali primerni za vgradnjo betametazondiproprionata in predstavljajo obetaven dostavni sistem za zdravljenje atopijskega dermatitisa. Atopic dermatitis is a chronic, non-infectious inflammatory skin disease accompanied by itching and recurrent eczematous lesions. Treatment is aimed at controlling and preventing inflammation and itching of the skin, also, regular, and proper skin care is of key importance. The first choice for the local treatment of atopic dermatitis are corticosteroids incorporated into classic pharmaceutical dosage forms such as creams and ointments. Therefore, the objective of our study was to contribute to the improved treatment of atopic dermatitis by incorporating betamethasone dipropionate into modern delivery systems, namely lyotropic liquid crystals. The latter are extremely favorable for dermal application due to their specific microstructure. In addition, the choice of excipients was crucial, with flaxseed or hemp oil being chosen as the oil phase due to its high content of essential fatty acids with anti-inflammatory action being beneficial for atopic skin, while the emulsifier phase consisted of biocompatible surfactants that promote the formation of lyotropic liquid crystals, namely lecithin in combination with Tween 80 or Montanov 68. Water was chosen as the hydrophilic phase. Within the experimental work, the areas of liquid crystal were determined based on organoleptical evaluation for four different combinations of oil phase and mixtures of surfactants by (pseudo)ternary phase diagrams construction. Selected samples (with and without incorporated betamethasone diproprionate) on the dilution line (i.e., at different water proportions) with a constant ratio of surfactants and oil phase 6/4 were used for further microstructure evaluation by polarization microscopy. For samples with Tween 80, the formation of lamellar liquid crystals was confirmed along the entire dilution line, while for Montanov 68 the formation of lamellar mesophases was confirmed only for specific samples depending on the proportions of the aqueous phase. The oil phase as well as the incorporation of the active substance did not affect the formation of lamellar liquid crystals. In the framework of further rheological analysis, we found that the incorporation of the active substance is reflected in the changed values of viscosity and dynamic modules in the case of samples with Tween 80. However, there were no significant changes in the samples with Montanov 68. Evaluation of the microstructure was performed at room temperature (25 °C), skin temperature (32 °C) and body temperature (37 °C), and the microstructure was maintained even at higher temperatures as confirmed by polarization, while temperature-dependent changes in viscosity were detected in case of certain samples. To conclude, the newly developed lyotropic liquid crystals are suitable for the incorporation of betamethasone diproprionate and represent a promising drug delivery system for the treatment of atopic dermatitis.

Askorbilpalmitat (AP) je amfifilni derivat vitamina C, ki izkazuje večjo stabilnost in enostavnejše prodiranje v kožo, vendar je njegova stabilnost zaradi hitre oksidacije, nezadovoljiva. Namen magistrskega dela je izboljšati kemijsko stabilnost AP, vgrajenega v lamelarne tekoče kristale za dermalno uporabo. Ovrednotili smo dva različna pristopa za povečanje stabilnosti AP, in sicer dodatek antioksidantov ali povišanje koncentracije AP. V prvem delu smo v okviru preliminarne študije (2 tedna) testirali vpliv dodatka antioksidantov (vitamin C in E, koencim Q10, kvercetin, butilhidroksitoluen, propilgalat), različnih koncentracij AP (5 % in 10 % napram 1 % (m/m)) na stabilnost AP v dveh sistemih tekočih kristalov s konstantnim razmerjem med lipofilno fazo in emulgatorsko zmesjo ob različnem deležu vodne faze (T1 z najmanjšim deležem vode ter T8 z največjim deležem vode). V sisteme z dodanim antioksidantom smo vgradili 1 % (m/m) antioksidanta in 1 % (m/m) AP. Preliminarno stabilnostno študijo smo izvedli v klimatski komori pri 40 °C in 75 % RV, kjer so bili vzorci zaščiteni pred svetlobo, ter vrednotili stabilnost AP s pomočjo tekočinske kromatografije ob času 0 in 2 tedna. Ugotovili smo, da je bil AP najstabilnejši pri obeh višjih koncentracijah in sočasni vgradnji vitamina C v primeru 1 % (m/m) AP. Na podlagi preliminarnih rezultatov smo nadalje zasnovali in izvedli stabilnostno študijo pri višjih koncentracijah AP ali ob dodatku vitamina C v tekočih kristalih z različno kvantitativno sestavo, in sicer v tekočih kristalih z naraščajočim deležem vode (TK1, TK3, TK5 in TK8) in primerjalno v SMES (zmes olja in emulgatorjev brez dodane vode). Vzorce smo shranjevali v klimatski komori pri 40 °C in 75 % RV in določali upad vsebnosti AP s tekočinsko kromatografijo znotraj 8 tednov. Ugotovili smo, da stabilnost AP z nižanjem deleža vode narašča. Najbolj optimalno stabilnost smo po osmih tednih dosegli v TK1 in SMES-u pri višjih koncentracijah AP ali ob dodatku antioksidanta vitamina C. Ker lahko večji delež vgrajenega AP ali dodatek antioksidantov vpliva na mikrostrukturo, smo mikrostrukturo tekočih kristalov, vključenih v stabilnostno študijo, dodatno pregledali pod polarizacijskim mikroskopom ter potrdili njihovo lamelarno strukturo. Zaključimo lahko, da smo z vgradnjo višjih koncentracij AP in dodatkom vitamina C v tekoče kristale z manjšim deležem vode, dosegli uspešno stabilizacijo AP. Ascorbyl palmitate (AP) is an amphiphilic derivative of vitamin C, which shows greater stability and easier penetration into the skin, but its stability is still insufficient due to rapid oxidation. The aim of master’s thesis is to improve the chemical stability of AP incorporated in lamellar liquid crystals for dermal application. Two different approaches to increase the stability of AP were evaluated, the addition of antioxidants or increasing the AP concentration. Firstly, the effect of antioxidants (vitamins C and E, coenzyme Q10, quercetin, butylhydroxytoluene, propyl gallate) and different concentrations of AP (5% and 10% vs. 1% (w/w)) on the stability of AP in two liquid crystal systems was tested within preliminary study (2 weeks). Liquid crystals had a constant ratio between lipophilic phase and emulsifier mixture at different proportions of aqueous phase (T1 with the lowest and T8 with the highest proportion of water). In the systems with added antioxidant, 1% (w/w) antioxidant and 1% (w/w) AP had been incorporated. A preliminary stability study was carried out at 40 °C and 75 % relative humidity, where the samples were protected from light, and the stability of AP was evaluated by liquid chromatography at 0 and 2 weeks. AP was most stable at both higher AP concentrations and with the additional incorporation of vitamin C in the case of 1% (w/w) AP. Based on the preliminary results, a stability study was further designed and carried out at either higher concentrations of AP or with the addition of vitamin C in liquid crystals. The tested liquid crystals differ in their quantitative composition, namely the water content was increasing from TK1, TK3, TK5 to TK8, comparatively the stability was evaluated also in SMES (mixture of oil and emulsifiers with no added water). The samples were stored at 40 °C and 75 % relative humidity and the decrease in concentration of AP was determined by liquid chromatography within 8 weeks. As determined, the stability of AP increased with decreasing water content. The most optimal stability was observed after 8 weeks in TK1 and SMES at higher AP concentrations or with the addition of the antioxidant vitamin C. Because the addition of antioxidants or increasing the concentration of AP influence the microstructure, the microstructure of the liquid crystals included in the stability study was examined under a polarized microscope and the lamellar structure was confirmed. It can be concluded that by incorporating higher concentrations of AP and the addition of vitamin C to the liquid crystals with a lower proportion of water, successful stabilization of AP was achieved.

Tekoči kristali predstavljajo vmesno stanje med tekočinami in trdnimi snovmi. S trdnimi snovmi jih povezujemo zaradi anizotropnosti, dvolomnosti, urejenosti in mehanske stabilnosti, tok pa odraža lastnost tekočin. Glede na njihov nastanek jih delimo na termotropne in liotropne. Liotropni obstajajo v več oblikah: lamelarni, kubični in heksagonalni. Lamelarni tekoči kristali predstavljajo aktualen dermalni dostavni sistem, predvsem zaradi podobnosti njihove strukturne urejenosti z medceličnimi lipidi rožene plasti kože. V okviru diplomskega dela smo na modelu in vitro na prašičji koži vpeti v Franz-ove difuzijske celice vrednotili vpliv lamelarnih tekočih kristalov na osnovi lecitina na barierno funkcijo kože, natančneje na transepidermalno izgubo vode in hidratacijo. Izdelali smo osem sistemov tekočih kristalov z različno kvantitativno sestavo (razmerje med oljno fazo in emulgatorsko zmesjo je bilo konstantno ob naraščajočem deležu vodne faze) in ugotavljali vpliv na vrednosti proučevanih parametrov. Najprej smo v sklopu preliminarnih testov določili čas predhodne hidratacije kože v Franz-ovih difuzijskih celicah za določitev bazalnih vrednosti, čas delovanja tekočih kristalov na koži in časovne točke za oceno učinka tekočih kristalov po odstranitvi s kože. Transepidermalno izgubo vode smo določali s Tewametrom® TM 300 in nato v enakih časovnih točkah še hidratacijo s Corneometrom® CM 825. Vrednosti, ki smo jih izmerili pred nanosom tekočih kristalov (bazalne vrednosti), smo primerjali s končnimi vrednostmi, tj. 30 min in 90 min po odstranitvi. Vsi sistemi tekočih kristalov so izboljšali barierno funkcijo, kar se je izražalo v znižanju transepidermalne izgube vode in zvišanju hidratacije. Največje znižanje TEWL je 30 min po odstranitvi TK s kože znašalo 18,6 %, po 90 min pa 22,3 %, medtem ko je bilo največje zvišanje hidratacije po 30 min za 158,3 %, po 90 min pa za 165,5 %. Izboljšanje barierne funkcije kože, zlasti hidratacije, je bilo odvisno od kvantitativno sestave tekočih kristalov, in sicer deleža oljne faza in emulgatorske zmesi, ki vplivata na nastanek semipermeabilnega filma na površini kože, prav tako je bil učinek časovno odvisen. Liquid crystals are considered to be an intermediate state between liquids and solids. They are associated with solids because of their anisotropy, birefringence, structure and mechanical stability, while their flowability correlate them with liquids. According to their origin, they are divided into thermotropic and lyotropic liquid crystals. Lyotropic ones exist in several forms: lamellar, cubic and hexagonal Lamellar liquid crystals represent the innovative dermal delivery system, mainly because of their structure, which is similar to that of the intercellular lipids of the stratum corneum of the skin. For the purposes of this thesis, the influence of lecithin-based lamellar liquid crystals on the skin’s barrier function, more precisely on transepidermal water loss and hydration, was evaluated in vitro on a porcine skin model embedded in Franz diffusion cells. Influence of eight liquid crystal systems with different quantitative compositions (while the proportion of the aqueous phase was rising, the ratio of the oil phase to the emulsifiers was constant) on the studied parameters was determined. First, as a part of the preliminary tests, we determined the time of the skin’s pre-hydration in Franz diffusion cells to determine basal values, the amount of time the liquid crystals were exposed to the skin, and time points to assess the effect of liquid crystals after removal from the skin. Transepidermal water loss was determined using the Tewameter® TM 300. Afterwards, the hydration was determined at the same time points using the Corneometer® CM 825. The values measured before the application of the liquid crystals (basal values) were compared with the final values, i.e. 30 minutes and 90 minutes after the liquid crystals had been removed. Following skin application, the liquid crystals improved the barrier function as seen in decreased transepidermal water loss and increased hydration. The maximum decrease in TEWL was 18,6 %, 30 minutes after, and 22,3 %, 90 min after the liquid crystal system had been removed from the skin. The maximum increase in hydration was 158,3 %, 30 minutes after, and 165,5 %, 90 min after the liquid crystal had been removed from the skin. The improvement of skin barrier function, especially hydration, correlates with quantitative composition of liquid crystals, namely the proportion of oil phase and emulsifier mixture, contributing to formation of semipermeable film on the skin surface. Moreover, the effect was time dependent.

Senzorična analiza je pomembno orodje za vrednotenje kozmetičnih izdelkov v celotni poti razvoja kozmetičnega izdelka, od konceptualizacije izdelka do marketinga in prodaje. Skupaj z instrumentalnimi testi daje dodatno vrednost in popolnejši profil kozmetičnega izdelka. Za razliko od instrumentalnih testov pri senzorični analizi kozmetični izdelek ocenjuje človek s svojimi osnovnimi čuti. To so vid, voh, tip, okus in sluh. Znotraj senzorične analize ločimo analitične in hedonske metode. Analitične imajo objektiven pristop, pri katerem sodeluje kvalificirano osebje, medtem ko je za hedonske metode značilen subjektiven pristop, pri katerem sodelujejo nekvalificirani prostovoljci. Znotraj vsake izmed metod ločimo več testov. Znotraj analitičnih metod ločimo diskriminatorno (trikotni test, duo-trio test, test s primerjavo v parih in uvrstitveni test) in deskriptivno (klasična kvantitativna deskriptivna analiza, metoda hitrega profiliranja, Pivot© profil metoda in metoda »označi, kar ustreza«) testiranje. Znotraj hedonskih metod ločimo afektivno in efektivno testiranje. Izbira testa je odvisna od cilja, ki ga želimo doseči. V diplomskem delu smo z anketnim raziskovanjem med devetimi slovenskimi in tujimi kozmetičnimi podjetji preučevali pristop k postavitvi senzoričnega profila izdelka. Gre za kozmetična podjetja in podjetja, ki se med drugim ukvarjajo tudi s senzorično analizo kozmetičnih izdelkov. Zanimalo nas je, na kakšen način so podjetja vpeta v senzorično analizo, katere izdelke vrednotijo in katerih testov se pri tem poslužujejo. Pridobili smo tudi podatke o lastnostih, izobrazbi in usposabljanju ocenjevalcev ter prostorih, kjer se senzorična analiza izvaja. Seznanili smo se tudi s potekom senzorične analize in vrednotenjem rezultatov le-te. Ugotovili smo, da vsa podjetja v določenem obsegu izvajajo senzorično vrednotenje kozmetičnih izdelkov, najpogosteje za kozmetične izdelke za lase. Največkrat uporabljajo hedonski pristop oz. potrošniške teste. Zanimiv odgovor sta nam podali slovenski podjetji Kozmetika Afrodita, d. o. o., in Hemptouch, d. o. o. Vprašanja, povezana s senzoriko, so namreč pri Afroditi zgolj del testiranja polizdelka v izbranih testnih skupinah. Pri tem nikoli ne sodelujejo usposobljeni preizkuševalci, temveč zgolj prostovoljci. Podjetje Hemptouch ne nameni veliko pozornosti ugodni senzorični izkušnji, saj je namen njihovih izdelkov reševanje kožnih težav. Kljub temu so se z zamenjavo sestavine zaradi neugodne senzorične izkušnje že srečali. Tako vidimo, da je senzorična analiza neizogibni in pomemben del vrednotenja kozmetičnih izdelkov. V drugem sklopu naloge smo na podlagi pridobljenih informacij v okviru anketnega raziskovanja in podatkov iz strokovne literature sestavili vprašalnik in izvedli senzorično analizo, kjer nas je zanimala predvsem povezava med zaznanimi lastnostmi ter trditvami za posamezen kozmetični izdelek. Izvedli smo hedonski oz. potrošniški test, in sicer kombinacijo afektivnega in efektivnega testa. Primerjali smo dve kremi za obraz znamke Afrodita, »Aqua MIX lahka hranljiva krema« in »Botanical MIX vlažilna gelna krema«. Kremi sta se med seboj razlikovali v določenih sestavinah, s čimer smo pojasnili razlike v senzoričnih lastnostih. Večina testirank bi raje izbrala »Botanical MIX vlažilno gelno kremo«, ki glede na informacije s strani proizvajalca dejansko dosega večji delež prodaje. V okviru testiranja smo prav tako potrdili večino navedb, s katerimi proizvajalec oglašuje oba kozmetična izdelka. V okviru diplomske naloge smo z anketnim raziskovanjem pridobili veliko informacij ter dobili vpogled v ključno vlogo senzorične analize tako pri razvoju kot marketingu kozmetičnih izdelkov. Sensory analysis is a tool for evaluating cosmetic products throughout the development path of a cosmetic product, starting from the conceptualization model to marketing and sales. Together with instrumental tests, it provides additional value and a complete profile of the cosmetic product. Unlike instrumental tests, sensory analysis is carried out by a person with its basic senses, namely sight, smell, touch, taste and hearing. Within sensory analysis, we distinguish between analytical and hedonic methods. Analytical methods have an objective approach involving qualified staff, while hedonic methods have more subjective approach involving unskilled volunteers. Within each method, there are several tests. Within analytical methods, we distinguish between discrimination (triangle test, duo-trio test, pairwise test and ranking test) and descriptive (classical quantitative descriptive analysis, flash profile method, pivot profile method and check-all-that-apply method) testing. Within hedonic methods, we distinguish between affective and effective testing. The choice of test depends on the goal we want to achieve. Within the diploma thesis, we studied the approach to setting up a sensory profile through a survey among nine Slovenian and foreign cosmetic companies. These are cosmetic companies and companies that are not cosmetic but are engaged in sensory analysis of cosmetic products. We were interested in how the companies are involved in sensory analysis, which products they value and which tests are used. We also obtained data on the characteristics, education and training of assessors and the places where sensory analysis is performed. We also got acquainted with the steps of sensory analysis and evaluation of its results. We found that each company performs a sensory evaluation of cosmetic products to a certain extent, most often for hair cosmetics. Hedonic approach or consumer tests are most often used. An interesting answer was provided by Slovenian companies Kozmetika Afrodita d. o. o. and Hemptouch d. o. o. In Afrodita sensory-related questions are only part of the testing of a semi-finished product in selected test groups. Qualified assessors are never involved, only volunteers. Hemptouch does not pay much attention to a favourable sensory experience, as the purpose of their products is to solve skin problems. Nevertheless, they have already encountered ingredient replacement due to an unfavourable sensory experience. We conclude that sensory analysis is an inevitable and important part of the evaluation of cosmetic products themselves. In the second part of the diploma thesis, based on the information obtained in the survey and data from the professional literature, we set up a questionnaire and performed a sensory analysis, where we were mainly interested in the correlation between perceived properties and claims for individual cosmetic products. We performed hedonic or consumer test, a combination of affective and effective test. We compared two Afrodita’s face creams, “Aqua MIX light nourishing cream” and “Botanical MIX hydrating gel cream”. Creams differ in certain ingredients, thus explaining the differences in sensory properties. Most opted for “Botanical MIX hydrating gel cream” over “Aqua MIX light nourishing cream”. According to the information from manufacturers “Botanical MIX hydrating cream” indeed achieves a higher share of sales. As part of the testing, we also confirmed most of the claims, with which manufacturers advertise both cosmetic products. Through survey research, we gained a lot of information and insight into the key role of sensory analysis in both the development and marketing of cosmetic products.

Področje učinkovitosti izdelkov z vgrajenimi kozmetično aktivnimi sestavinami za povečanje prekrvitve je slabo raziskano, saj je podatkov o njihovem delovanju po nanosu na kožo zelo malo. Klasične kozmetično aktivne sestavine za povečanje prekrvitve, kot so mentol, kafra, kapsaicin, escin, arginin idr. najpogosteje zasledimo v športni kozmetiki in izdelkih za lajšanje mišično-skeletnih bolečin, v katerih naj bi po njihovem nanosu na kožo z delovanjem na temperaturno občutljive receptorje v koži povzročile vazodilatacijo in povečano prekrvitev kože. Poleg številnih metod, ki prekrvitev kože določajo neposredno z merjenjem krvnega pretoka kože, pa obstajajo metode, s katerimi merimo spremenljivke, ki odražajo spremembe v prekrvitvi kože. V okviru in vivo študije smo tako učinkovitost izdelkov z vgrajenimi kozmetično aktivnimi sestavinami za povečanje prekrvitve vrednotili posredno preko spremembe temperature kože, in sicer s termovizijsko kamero, ki izkorišča pojav sevanja infrardečega valovanja s površine kože. V diplomski nalogi smo vrednotili vpliv štirih različnih izdelkov na temperaturo kože, ki so se med seboj razlikovali glede na aktivno sestavino za povečanje prekrvitve (mentol, kafra, kapsaicin), tehnološko obliko (hidrogel, lipofilna krema) in skupino izdelka (kozmetični izdelek, medicinski pripomoček, zdravilo brez recepta). Na podlagi rezultatov smo ugotovili, da so izdelki z vgrajenim mentolom izkazali enak časovno odvisen učinek, in sicer takoj po nanosu statistično značilno znižanje temperature kože glede na bazalno vrednost, po 5 minutah od nanosa pa statistično značilno povišanje glede na vrednosti takoj po nanosu. Enak trend spreminjanja temperature smo prav tako opazili pri izdelku, ki poleg mentola vsebuje tudi kafro. Pri izdelku z vgrajenim kapsaicinom tekom meritev ni prišlo do statistično značilnih sprememb v temperaturi kože. Ugotovili smo, da so statistično značilne razlike v spremembi temperature kože med izdelki prisotne v intervalu prvih 5 minut, in so najverjetneje posledica različne sestave oz. tehnološke oblike izdelkov. Zaključimo lahko, da termografija kot komplementarna tehnika za vrednotenje temperature kože predstavlja inovativen in perspektiven način spremljanja učinkovitosti KAS za povečanje prekrvitve v prihodnje. The efficacy of products with rubefacients is poorly understood as there is very little data on how they work following application on the skin. Typical rubefacients, such as menthol, camphor, capsaicin, aescin, arginine, etc., are most commonly found in sports cosmetics and musculoskeletal pain relief products, which when applied on the skin, are thought to cause vasodilatation and increased blood flow to the skin by activating temperature-sensitive receptors. In addition to the many methods that determine skin blood flow directly, others measure variables indicating changes in skin blood flow. Thus, within performed in vivo study, the efficacy of products with rubefacients was evaluated indirectly by measuring change in skin temperature, using a thermal imaging camera that utilises the appearance of infrared radiation on the surface of the skin. In the thesis, the effect of four different products, differing in the incorporated rubefacient (menthol, camphor, capsaicin), technological form (hydrogel, lipophilic cream) and product group (cosmetic product, medical aid, nonprescription medicine), on skin temperature was evaluated. The results showed that products with menthol had the same time-dependent effect, i.e. a statistically significant decrease in skin temperature immediately after application compared to the basal value, and a statistically significant increase in skin temperature five minutes after application compared to the values immediately after application. The same trend of temperature changes was observed while testing the product which, in addition to the menthol, contained camphor. The product with capsaicin did not cause statistically significant changes in skin temperature during the measurements. Statistically significant differences in skin temperature change between the products were observed during the first five minutes and are most likely due to the different composition or technological formulation of the products. In conclusion, thermography as a complementary technique for skin temperature evaluation represents an innovative and promising method for monitoring the efficacy of rubefacients in further studies.

Orodisperzibilni filmi (ODF) predstavljajo inovativen dostavni sistem, v katerega lahko vgrajujemo zdravilne učinkovine za lokalno in sistemsko dostavo. Zdravilna učinkovina se v nekaj sekundah po aplikaciji ODF sprosti v ustno votlino, s čimer dosežemo hiter začetek delovanja. V ODF lahko vgrajujemo različno velike odmerke, ki jih tako prilagodimo pediatrični populaciji ali pa predstavljajo alternativo tabletam zlasti za geriatrično populacijo, ki se sooča z oteženim požiranjem. V okviru magistrske naloge smo razvijali in vrednotili ODF z vgrajenim ibuprofenom (IBU) kot modelno učinkovino. ODF so izdelani na osnovi nanokristalne celuloze (NCC) dveh različnih proizvajalcev (NCC v prahu in gelu) v kombinaciji s tremi različnimi naravnimi polimeri (nizko viskozen hitosan, pektin in alginat) in glicerolom. NCC je naraven polimer, ki v vsaj eni dimenziji ne presega 100 nm, naravni polimeri pa povečajo premreženost polimernih verig in izboljšajo mehanske lastnosti hidrogelske rešetke. V prvem delu smo se osredotočili na vgradnjo IBU kot modelne slabo vodotopne zdravilne učinkovine (ZU) v hidrogele. Slabo topnost smo rešili s predhodno vgradnjo IBU v samo(mikro)emulgirajoči sistem, tj. zmes površinsko aktivne snovi in olja. Izdelane hidrogele smo nato reološko ovrednotili z vidika vpliva naravnega polimera ter vgrajene ZU na viskoznost in vrednosti elastičnega/plastičnega modula. Iz hidrogelov smo nadalje izdelali ODF z metodo izhlapevanja topila, kot najprimernejši za izdelavo so se izkazali filmi narejeni s pomočjo naravnega polimera alginata. Izdelanim filmom smo določili totalno vsebnost in ugotovili, da je v filmih, izdelanih na osnovi NCC v gelu, vsebnost IBU višja, kar nakazuje na večjo sposobnost vezave IBU z NCC v gelu. Z DSC smo potrdili, da je IBU v ODF prisoten v raztopljeni obliki. Čas razpadnosti filmov smo določali s pomočjo dveh različnih metod, klasično farmakopejsko metodo in kapljično metodo, novejšim pristopom za določanje časa razpadnosti. Daljše čase pri kapljični metodi pripisujemo temu, da ODF najprej počasi nabreka in šele nato razpade. V obeh primerih se je nakazal enak trend, in sicer da ODF na osnovi NCC v gelu razpadajo hitreje od paralel na osnovi NCC v prahu, ter da so časi razpadnosti najkrajši pri pektinu, sledi alginat, medtem ko ODF, narejeni s pomočjo hitosana, zaradi njegove netopnosti pri nevtralnem pH v vodi ne razpadajo. Na podlagi vseh zbranih rezultatov, lahko zaključimo, da so ODF s pektinom in alginatom primerni za vgradnjo IBU, smiselno pa bi bilo raziskati še sproščanje iz teh filmov. Orodispersible films (ODF) represent an innovative drug delivery system in which active pharmaceutical ingredients for local or system delivery can be incorporated. The active pharmaceutical substance is released into the oral cavity within a few seconds after the application of ODFs, thus achieving a rapid onset of action. A range of doses can be incorporated into ODFs, i.e. adapted for the pediatric population. At the same time, the ODFs represent an alternative to tablets within the geriatric population who have difficulties with swallowing. Within the master's thesis, ibuprofen-loaded nanocellulose-based ODFs were developed and evaluated. ODFs are based on nanocrystalline cellulose (NCC) from two different manufactures (i.e. powder or gel NCC) in combination with three various natural polymers (low viscosity chitosan, alginate, and pectin) and glycerol. NCC is a natural polymer that does not exceed 100 nm in at least one dimension, while natural polymers do increase crosslinking of the polymer chains and improve the mechanical properties of the hydrogel network. In the first part of the thesis, we focused on the incorporation of ibuprofen as a model for poorly water-soluble active pharmaceutical ingredient into hydrogels. Poor solubility was resolved with pre-incorporation of ibuprofen into the self-microemulsifying system, consisting of surfactant and oil. Hydrogels were rheologically evaluated in terms of natural polymer and integrated active pharmaceutical ingredients influence on the viscosity and values of the elastic/plastic module. ODFs were then produced from hydrogels by the solvent casting method. Films made with natural polymer alginate proved to be the most suitable for production. Total content of the the produced ODFs was determined with the higher ibuprofen content in ODFs based on gel NCC, which indicated a higher ability to bind ibuprofen with gel NCC. As confirmed by DSC method the ibuprofen is present in dissolved form in the ODFs. The disintegration time of the films was determined using two methods: the classical pharmacopeia method and the drop method, a newer approach for determining disintegration time. The longer times in the droplet method are attributed to the fact that ODFs at first slowly swell and then disintegrate. With both methods, the same trend was observed, namely thet gel NCC based ODFs disintegrate faster than their powder NCC based ODFs parallels. The disintegration times are the shortest for pectin, followed by alginate, while ODFs made with chitosan, which is insoluble at neutral pH, do not disintegrate in water. Based on all the obtained results, we can conclude that ODFs with pectin and alginate are suitable for ibuprofen incorporation, and it would be reasonable to explore the release from these ODFs as well.

Izrazite trepalnice veljajo za znak lepote, zato ni presenetljivo, da obstaja na trgu veliko različnih kozmetičnih izdelkov, katerih namen je polepšati videz zdravih trepalnic. Za najbolj pogosto uporabljen kozmetični izdelek za dekorativo oči velja maskara, ki začasno ustvari videz gostejših in podaljšanih trepalnic. Trajnejše rezultate pa lahko dosežemo z ostalimi izdelki, kot so na primer serumi za rast trepalnic. Namen slednjih je povečati dolžino, pigmentacijo, ukrivljenost in debelino trepalnice, kar z eno besedo imenujemo trihomegalija. V diplomskem delu smo proučevali sestavo serumov za rast trepalnic, pri čemer smo v nabor nabor vključili 38 izdelkov. Osredotočili smo se na kozmetično aktivne sestavine, ki smo jih razdelili po skupinah glede na kemijsko sestavo in vrednotili njihovo pojavnost v izbranih izdelkih. Za vsako sestavino je opisan mehanizem delovanja na rast trepalnic. Zanimali so nas tudi podatki o ceni, oglaševanju in ovojnini, ki odločilno vplivajo na odločitev pri nakupu izdelka. Kozmetično aktivne sestavine smo razdelili v pet skupin, in sicer si po pogostosti uporabe v serumih sledijo v naslednjem zaporedju: vitamini, peptidi, aminokisline, analogi prostaglandinov in ostale sestavine. Navadno je v enem serumu prisotnih več različnih kozmetično aktivnih sestavin. Mehanizem delovanja se med skupinami razlikuje. Pri vitaminih in aminokislinah ne gre za direkten vpliv na rast trepalnice, ampak vplivajo na strukturo trepalnice in omogočajo normalno rast. Peptidi imajo več različnih mehanizmov delovanja odvisno od peptida, najpogosteje povečajo prekrvavitev in proliferacijo keratinocitov v mešičku trepalnice. Analogi prostaglandinov imajo značilen mehanizem delovanja, in sicer trihomegalijo trepalnic dosežejo z vezavo na prostanoidni receptor na celicah mešička, ki povzroči podaljšanje anagene faze in spodbujanje prehoda mešička trepalnice iz telogene faze v anageno fazo. Poleg tega analogi prostagladinov veljajo za edine kozmetične aktivne sestavine, ki imajo s kliničnimi študijami podprto delovanje na rast trepalnic. Pri vrednotenju cene izdelkov smo opazili, da je ta odvisna od vsebnosti analogov prostaglandinov, ki prispevajo k višji ceni. Vsi pregledani serumi se nahajajo v tubularnih vsebnikih, ki omogočajo nanos na veko. Prominent eyelashes are considered as a sign of beauty, consequently contributing to many diverse cosmetic products on the market intended to beautify the look of healthy eyelashes. The most commonly used cosmetic product for eye decoration is mascara, which temporarily creates the appearance of thicker and longer lashes. More lasting results can be achieved using other products, including eyelash growth serums that increase the length, pigmentation, curvature and thickness of the eyelashes, namely trichomegaly. Within the diploma thesis, the composition of 38 eyelash growth serums was studied. Special emphasis was given towards cosmetically active ingredients, divided into groups according to chemical composition, and their occurence in selected products. For each component, the mechanism of action on eyelash growth is described. Price, advertising and packaging was also evaluated having a decisive role when purchasing a product. Cosmetically active ingredients are divided into five groups, according to the frequency of use in serums as follows: vitamins, peptides, amino acids, prostaglandin analogues and other ingredients. Usually, several different cosmetically active ingredients are present in one serum. The mechanism of action varies between groups. Vitamins and amino acids do not have a direct effect on eyelash growth, but rather affect the structure of the eyelash and allow normal growth. Peptides have several different mechanisms of action depending on the peptide, most commonly increasing blood flow and keratinocyte proliferation in the eyelash follicle. Prostaglandin analogues have a specific mechanism of action. Trichomegaly of eyelashes is achieved by binding prostaglandin analogues to the prostanoid receptor on follicular cells, which causes prolongation of the anagen phase and stimulates the transition of the eyelash follicle from the telogen phase to the anagen phase. In addition, prostaglandin analogues are considered the only cosmetic active ingredients that have a clinical study-supported effect on eyelash growth. The price of products depends on the content of prostaglandin analogues, contributing to the higher price. All examined serums are found in tubular containers that allow application to the eyelid.

Atopijski dermatitis (AD) je nenalezljiva, kronična vnetna bolezen kože, ki prizadene 10–30 % otrok in 2–10 % odraslih. Atopijska koža je suha in občutljiva, spremlja jo srbenje. Poškodbe kožne bariere, značilne za AD, nastanejo pod vlivom prepleta genetskih, okoljskih in vnetnih dejavnikov. Pomembno vlogo pri obvladovanju AD ima vsakodnevna nega kože ter izogibanje alergenom in sprožilcem vnetja, ki lahko poslabšajo stanje, pri zdravljenju pa v prvi vrsti uporabljamo lokalno protivnetno terapijo, pri hujših oblikah tudi sistemsko terapijo. Poleg konvencionalnih dermalnih farmacevtskih oblik se za zdravljenje AD raziskuje tudi uporaba hidrogelov. Slednje definiramo kot tridimenzionalne strukture polimernih verig t. i. tvorilcev gela, ki imajo sposobnost nabrekati in znotraj svojega ogrodja zadržati večje količine vode. V okviru magistrske naloge smo razvijali in vrednotili hidrogele na osnovi nanokristalne celuloze (NCC) dveh različnih proizvajalcev, ki sta se razlikovali tudi v makroskopskem videzu (tj. gelska ali praškasta NCC). Poleg NCC so hidrogele sestavljali tudi eden izmed treh različnih naravnih polimerov (alginat, pektin ali nizko viskozni hitosan), glicerol in betametazondipropionat (BDP) kot modelna zdravilna učinkovina (ZU), ki se sicer uporablja za zdravljenje AD. Najprej smo se osredotočili na optimizacijo vgradnje BDP v obliki samo-mikroemulgirajočega sistema (SMES) v hidrogele. Z metodo diferenčne dinamične kalorimetrije (DSC) smo potrdili, da je v hidrogele vgrajena ZU raztopljena. Z reološkimi meritvami smo ovrednotili vpliv dveh različnih NCC in SMES na viskoznost in amplitudno ter frekvenčno odvisnost elastičnega in plastičnega modula. Ugotovili smo, da NCC v obliki praška tvori bolj viskozne hidrogele, medtem ko dodatek SMES (z ali brez vgrajenega BDP) lahko ali zviša ali zniža viskoznost hidrogela oziroma vrednosti enega ali obeh modulov, odvisno od uporabljenega naravnega polimera in NCC. Nadalje smo iz hidrogelov z vgrajenim SMES (z in brez BDP) z metodo izhlapevanja topila pripravili filme. Pripravljeni filmi so izkazali nizko vsebnost zaostale vlage (do 2,15 % m/m), njihova debelina pa je znašala največ 0,090 ± 0,007 mm. Pripravljeni filmi so izkazali statistično značilno razliko v sposobnosti zadrževanja vode po namestitvi na membrano iz celuloznega acetata. Izdelani hidrogeli so se izkazali kot potencialni dostavni sistemi za BDP pri zdravljenju AD. Atopic dermatitis (AD) is a non-contagious chronic inflammatory skin disease with the lifetime prevalence estimated to be 10–30 % in children and 2–10 % in adults. Atopic skin is characterised as dry and sensitive, accompanied by itch. Skin barrier dysfunction, distinctive in AD, occur under the influence of a mix of genetic, environmental and inflammatory factors. Daily skin care routine and the avoidance of allergens and the inflammation triggers that can worsen the condition have important role in the management of AD, while in the treatment, initially local anti-inflammatory therapy, and in severe AD, also systemic therapy is used. In addition to conventional dermal pharmaceutical forms, the use of hydrogels is also being investigated for the treatment of AD. Hydrogels are defined as three dimensional polymeric networks of gelling agents with the ability of swelling and holding a large quantity of water within its scaffold. Within the master's thesis hydrogels based on nanocrystalline cellulose (NCC) from two different manufacturers, differing also in macroscopic characteristics (i.e. gel or powder NCC), were developed and evaluated. Beside NCC, hydrogels also consisted of one of three different natural polymers (alginate, pectin or low viscosity chitosan), glycerol, and betamethasone dipropionate (BDP) as model active pharmaceutical intgredient (API) otherwise used to treat AD. We first focused on optimizing the incorporation of BDP in the form of a self-microemulsifying system (SMES) into hydrogels. The differential scanning calorimetry (DSC) method confirmed that the API incorporated in the hydrogels was dissolved. The influence of two different NCC and SMES on the viscosity and amplitude and frequency dependence of the elastic and plastic modulus was evaluated by rheological measurements. The powderish NCC was found to form more viscous hydrogels while the addition of SMES (with or without incorporated BDP) either increased or decreased the viscosity or the values of one or both modules, depending on the natural polymer and NCC used. Furthermore, films were prepared from hydrogels containing SMES (with and without BDP) using the solvent evaporation method. The prepared films showed a low residual moisture content (up to 2,15 % m/m) and a maximum thickness of 0,090 ± 0,007 mm. In addition, the prepared films showed a statistically significant difference in water retention ability after application to a cellulose acetate membrane. The hydrogels produced have proven to be potential delivery systems for BDP in the treatment of AD.

Prihodnost farmacevtske obravnave in razvoja zdravil vse bolj sloni na ideji personalizirane skrbi za pacienta. V tem oziru se kot inovativni dostavni sistem uveljavljajo orodisperzibilni filmi (ODF). V slednje tako lahko vgrajujemo različne velikosti odmerkov prilagojenih pediatrični populaciji, medtem ko predstavljajo za geriatrično populacijo, ki se sooča z oteženim požiranjem, kakovostno alternativo tabletam. Z ODF zagotovimo tudi boljšo vodljivost pri hospitaliziranih bolnikih, kjer obstaja verjetnost, da bolniki tableto naknadno izpljunejo. V okviru magistrske naloge smo razvijali in vrednotili ODF na osnovi nanokristalne celuloze (NCC) dveh različnih proizvajalcev, ki sta se razlikovali tudi v makroskopskem videzu (tj. praškasta ali gelska NCC). Najprej smo razvijali sestavo hidrogelov iz NCC, treh različnih naravnih polimerov (alginat, pektin ali nizko viskozni hitosan), glicerola in kalcijevih ionov. NCC je naravni polimer, ki vsaj v eni dimenziji ne presega 100 nm, naravni polimeri pa povečajo premreženost polimernih verig in izboljšajo mehanske lastnosti hidrogelske rešetke. V drugem delu naloge smo z reološkimi meritvami ovrednotili vpliv dveh različnih NCC in kalcijevih ionov na viskoznost in frekvenčno odvisnost elastičnega in plastičnega modula. Želeli smo namreč ugotoviti vpliv reoloških parametrov na debelino in mehanske lastnosti ODF. Ugotovili smo, da NCC v obliki praška tvori bolj viskozne hidrogele, medtem ko dodatek kalcijevih ionov lahko ali zviša ali zniža viskoznost hidrogela, odvisno od uporabljenega naravnega polimera. Na podlagi frekvenčne odvisnosti elastičnega in plastičnega modula pri hidrogelih z alginatom in pektinom smo ugotovili, da večja razlika med moduloma prispeva k boljšim mehanskim lastnostim ODF. Nadalje smo ugotovili , da je moč gelske mreže odvisna od koncentracije NCC, kemizma uporabljenega naravnega polimera in dodatka kalcijevih ionov. V tretjem delu naloge smo vrednotili še čas razpada ODF ter mehanske lastnosti z nateznim testiranjem. Najvišjo natezno trdnost, kljub neoptimalnim reološkim lastnostim hidrogela, so dosegali ODF pripravljeni iz gelske NCC in nizko viskoznega hitosana, najvišje vrednosti Young-ovega modula in maksimalnega relativnega raztezka pa ODF iz NCC v obliki praška in alginata. Najprimernejši ODF glede na natezno testiranje so bili tisti iz praškaste NCC in alginata ali pektina, saj so imeli visoke vrednosti natezne trdnosti, visok Young-ov modul in maksimalni relativni raztezek višji od 10 %. Nadalje smo s testom časa razpada v povezavi z mehanskimi lastnostmi ugotovili, da imajo ODF iz pektina najprimernejši čas razpada in omogočajo najlažje rokovanje. Na podlagi vseh zbranih rezultatov lahko zaključimo, da so razviti ODF s pektinom in alginatom, ne glede na vrsto dodane NCC, najbolj primerni za nadaljnji razvoj FO. The future of pharmaceutical treatment and drug development is more and more based on the idea of personalised patient care. In this context orodispersible films (ODF) are gaining importance as an innovative drug delivery system. Namely, different dose sizes adapted to the pediatric population can be incorporated into ODF, while within geriatric populations who have difficulty in swallowing, ODF represent a quality alternative to tablets. In addition, better manageability of hospitalised patients who are likely to spit out the tablet afterwards can be achived. Within the master's thesis the development and evaluation of ODF was based on nanocrystalline cellulose (NCC) from two different manufacturers, differing also in macroscopic characteristics (i.e. powder or gel NCC). Firstly the optimal composition of hydrogels from NCC, three different natural polymers (alginate, pectin or low viscosity chitosan), glycerol, and calcium ions, was developed. NCC is a natural polymer that does not exceed 100 nm in at least one dimension, while natural polymers increase crosslinking of the polymer chains and improve the mechanical properties of the hydrogel network. In the second part of the thesis, the influence of two different NCC and calcium ions on the viscosity and frequency dependence of the elastic and plastic modulus was evaluated by rheological measurements. Specifically, we wanted to ascertain whether rheological parameters affect the thickness and mechanical properties of ODF. The powderish NCC was found to form more viscous hydrogels and that the addition of calcium ions either increased or decreased the viscosity depending on the natural polymer used. Based on the frequency dependence of the elastic and plastic modulus of hydrogels with alginate and pectin, it was observed that the difference between the modules should be as large as possible for good mechanical properties of ODF. Also, the strength of the gel network was found to depend on the NCC concentration, the chemistry of the natural polymer used, and the addition of calcium ions. In the third part of the thesis, ODF’s disintegration time plus mechanical properties within tensile testing were evaluated. The highest tensile strength, despite unfavourable rheological values of the hydrogel, was achieved by ODF prepared from gelish NCC and low viscosity chitosan, the highest values of Young's modulus and maximum relative elongation were achieved by ODF with powderish NCC and alginate. The most suitable ODF based on tensile testing results were those with powderish NCC and alginate or pectin, as they had high tensile strength, high Young’s modulus and a maximum relative elongation greater than 10 %. Furthermore, by employing the disintegration time test in conjunction with the mechanical properties of ODF, it was found that ODF from pectin have the most suitable disintegration time and allow the easiest handling. Based on all the results, ODF developed with pectin and alginate, regardless of the NCC type added, are considered as the most suitable for the further development of dosage form.

Lamelarni tekoči kristali zaradi svoje strukture in lastnosti predstavljajo fiziološko sprejemljiv dostavni sistem za dermalno uporabo, v katerega lahko vgradimo lipofilne, hidrofilne ali amfifilne spojine. Askorbilpalmitat je znan antioksidant, ki se pogosto uporablja v farmaciji in kozmetiki. Je zelo občutljiva in nestabilna amfifilna snov, katere razpad povzročijo številni dejavniki, kot so svetloba, kisik, vlaga ali neustrezna sestava formulacije. V prvem delu magistrske naloge smo ovrednotili stabilnost askorbilpalmitata, vgrajenega v osem sistemov tekočih kristalov (TK 1-TK 8), s konstantnim razmerjem lipofilnih in površinsko aktivnih snovi ob naraščajočem deležu vode kot hidrofilne faze. Preden smo vzorce tekočih kristalov z vgrajenim askorbilpalmitatom izpostavili staranju, smo nadgradili že obstoječo HPLC metodo za analizo askorbilpalmitata. HPLC metodo smo ustrezno optimizirali in validirali, in sicer z vidika selektivnosti, ponovljivosti, točnosti, linearnosti in stabilnosti. Nadalje smo v okviru 56-dnevne pospešene stabilnostne študije ugotovili, da stabilnost askorbilpalmitata z večanjem deleža vode v sistemih tekočih kristalov pada. Sistemi tekočih kristalov z manjšim deležem vode so bili stabilnejši (TK 1-TK 5) glede na sisteme z večjim deležem vode (TK 6-TK 8). Po 28 dneh shranjevanja pri 40 °C in 75 % relativni vlažnosti je bil askorbilpalmitat najbolj stabilen, ko je bil vgrajen v TK 1 (20 % (m/m) vode v sestavi), najmanj pa v sistemu TK 8 (55 % (m/m) vode v sestavi). Na podlagi izračunanih konstant reakcijske hitrosti in R2 smo ugotovili, da kinetika kemijskih reakcij razgradnje askorbilpalmitata sledi 1. redu. Iz vrednosti konstant reakcijske hitrosti je bila razvidna padajoča stabilnost od TK 1 (0,023 d-1) proti TK 8 (0,043 d-1), saj se je z večanjem deleža vode konstanta večala. V drugem sklopu naloge smo vrednotili in vitro sproščanje askorbilpalmitata iz izbranih sistemov tekočih kristalov skozi umetno membrano s pomočjo Franz-ovih difuzijskih celic. Predpostavili smo, da bo sproščanje odvisno od notranje strukture in viskoznosti sistemov, kar se spreminja glede na delež vode. Hitrejše sproščanje in v večjem obsegu smo tako potrdili za sisteme TK 1-TK 4, ki imajo manjši delež proste vode v interlamelarnem prostoru in tako manjše razdalje med lamelami, v primerjavi s TK 5-TK 8, kjer se zaradi naraščajočega deleža vode razdalje med lamelami večajo ob sočasni prisotnosti micelov. Zaključili smo, da lahko tekoče kristale uporabljamo kot dostavne sisteme za podaljšano sproščanje in da le-ti predstavljajo obetaven dostavni sistem za dermalno aplikacijo askorbilpalmitata. Lamellar liquid crystals have been due to their unique structure and properties used as dermal delivery system for lipophilic, hydrophilic or amphiphilic compounds. Ascorbyl palmitate is a well-known antioxidant that is widely used in pharmacy and cosmetics. It is considered as a very unstable amphiphilic compound, which degrades under the influence of light, oxygen, temperature, humidity as well as in suboptimal formulations. In the first part of the thesis we evaluated the stability of ascorbyl palmitate incorporated in eight different systems of liquid crystals (TK 1-TK 8), with a constant ratio of lipophilic compounds and surfactants and with increasing water content as hydrophilic compound. Before the stability study the present HPLC method for ascorbyl palmitate determination was upgraded. Namely, the method was optimized and validated by evaluating the selectivity, repeatability, accuracy, linearity and stability. Further, as a part of the 56-day study we showed that the stability of ascorbyl palmitate was decreasing with increased water content in liquid crystals. Stability of ascorbyl palmitate was better in liquid crystals with lower water content (TK 1-TK 5) compared to liquid crystals with higher water content (TK 6-TK 8). After 28 days of storage at 40 °C and 75 % relative humidity TK 1 (20 % (w/w) of water content) was the most stable system and TK 8 (55 % (w/w) of water content) was considered to be the least stable system. Based on calculated reaction rate constants and R2 we determined that kinetics of chemical reactions of ascorbyl palmitate follows 1. order. Values of the reaction rate constants showed a decreasing stability from TK 1 (0,023 d-1) to TK 8 (0,043 d-1) as the constant increased with increasing water content. In the second part of the thesis we evaluated in vitro release of ascorbyl palmitate from eight systems of liquid crystals. The study was performed on an artificial membrane using Franz diffusion cells. We assumed that the release would depend on the internal structure and viscosity of the systems, which varies with the proportion of water. Therefore, a faster release and to a greater extent was confirmed for systems TK 1-TK 4, which contained smaller amounts of free water in the interlamellar spacing and thus shorter distances between lamellaes, compared to systems TK 5-TK 8, where due to increasing water content the distances between lamellaes are increasing in the presence of micelles. We concluded that liquid crystals can be used as delivery system for sustained release and that they show a great potential as dermal delivery system.

Liotropni tekoči kristali z lamelarno strukturo so zaradi svoje termodinamske stabilnosti, enostavne izdelave, velike solubilizacijske kapacitete in hkrati strukturne podobnosti z roženo plastjo kože ter ugodnih učinkov na njeno hidratacijo vedno bolj proučevani kot dermalni nosilni sistemi ter zagotovo premalo zastopani na trgu, kjer prevladujejo klasične emulzije, geli itd.. Da lahko v polni meri izkoristimo učinke kozmetično aktivnih sestavin, jih moramo namreč vgraditi v ustrezno podlago, da zagotovimo optimalno stabilnost in dermalno absorpcijo ter tako dosežemo željen učinek. Pri načrtovanju nosilnega sistema na osnovi tekočih kristalov moramo zagotoviti, da vgrajene kozmetično aktivne sestavine ne spremenijo ali podrejo mikrostrukture, slednja je namreč ključna za njihove prednosti pri nanosu na kožo. Na podlagi tega nas je v okviru diplomske naloge zanimalo, kako vgradnja izbranih kozmetično aktivnih sestavin vpliva na mikrostrukturo tekočih kristalov. Slednjo smo ovrednotili z metodo elektronske paramagnetne resonance. V izbran sistem tekočih kristalov z lamelarno strukturo smo želeli vgraditi tri različne kozmetično aktivne sestavine, ki se med seboj razlikujejo v topnosti, ter v različnih deležih (m/m %). V sistem smo uspeli vgraditi dekspantenol, ki je analog pantotenske kisline (vitamina B5) ter tokoferil acetat, ki deluje kot antioksidant. Dekspantenol smo vgradili v različnih deležih, in sicer 0%, 1%, 2%, 5%, 7,5%, 10%, 15% ali 30%, tokoferil acetat pa v 5% deležu. Alantoina pa nismo uspeli vgraditi, ker se ni raztapljal v izbranem sistemu. Nadalje smo jih označili z izbranimi spinskimi označevalci, kar je ključen korak pri meritvah z elektronsko paramagnetno resonanco, saj preko spinskih označevalcev dobimo informacije o mikrostrukturi tekočih kristalov. Ugotovili smo, da različni deleži dekspantenola ne spremenijo značilno mikrostrukture tekočih kristalov. Razlika je bila očitna le pri višjih koncentracijah, saj je imel maksimalni hiperfini razcep večjo vrednost, kar nakazuje na bolj urejeno strukturo. Čeprav bi bilo optimalno vgraditi različne deleže tokoferil acetata v tekoče kristale, so rezultati pri 5% deležu spodbudni, saj večjega odstopanja v primerjavi s kontrolnim vzorcem nismo zaznali. Dekspantenol in tokoferil acetat torej na strukturo tekočih kristalov ne delujeta destruktivno, prav tako pa ne izzoveta faznih prehodov pri spremembi temperature, kar je za razvoj kozmetičnega izdelka ugodno. Liotropic liquid crystals with lamellar structure have been, due to their thermodynamic stability, ease of manufacture, high solubilization capacity as well as structural similarity to the corneal skin layer and their beneficial effects on hydration, increasingly studied as dermal carrier systems and certainly underrepresented in the market, dominated by classic emulsions, gels, etc. In order to take full advantage of the effects of cosmetically active ingredients, they must be incorporated into a suitable vehicle to ensure optimal stability and dermal absorption, and thus achieve the desired effect. When designing a carrier system based on liquid crystals, we have to ensure that the incorporated cosmetically active ingredient(s) do not alter or disrupt their microstructure, the latter being crucial for their advantages in applying it to the skin. On this basis within this diploma thesis, we were interested in how the incorporation of the selected cosmetically active ingredients affects the microstructure of liquid crystals. The latter was evaluated by the electron paramagnetic resonance method. Three different cosmetically active ingredients with different solubility and in different ratios (w/w %) were incorporated into the selected system of liquid crystals with lamellar structure. Into the system, we also managed to incorporate dexpanthenol, which is an analogue of pantothenic acid (vitamin B5) and tocopherol acetate, which acts as an antioxidant. The dexpanthenol was then incorporated in shares of 0 %, 1 %, 2 %, 5 %, 7.5 %, 10 %, 15 % or 30 %, and tocopherol in share of 5 %. However, we could not incorporate allantoin because it did not dissolve in the selected system. We further labelled them with selected spin labels, which is a key step in electron paramagnetic resonance measurements, as the information on the microstructure of liquid crystals is obtained through spin labels. Different ratios of dexpanthenol did not significantly alter the microstructure of the liquid crystals. The structural differences were only observed at higher ratios due to the observed higher value of maximum hyperfine splitting, suggesting a more orderly structure. Although it would be optimal to incorporate different proportions of tocopherol acetate in liquid crystals, the results are encouraging, at 5 %, since no significant deviation from the sample without cosmetically active ingredient was detected. Dexpanthenol and tocopherol acetate, therefore, do not have a destructive effect on the liquid crystal structure nor do they cause phase transitions, which is advantageous for the development of cosmetic products.