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This study aims to highlight the importance of choosing the appropriate co-polymer or co-polymer mixed combinations in order to design value-added nasal dosage forms. Local therapy of upper respiratory tract-related infections, such as nasal rhinosinusitis is of paramount importance, thus advanced local therapeutic options are required. Dexamethasone was encapsulated into three different polymeric micelle formulations: Soluplus or TPGS-only and their mixed combinations. Dynamic light scattering measurements proved that the particles have a micelle size less than 100 nm in monodisperse distribution, with high encapsulation efficiency above 80% and an at least 7-fold water solubility increase. Tobramycin, as an antimicrobial agent, was co-formulated into the in situ gelling systems which were optimized based on gelation time and gelation temperature. The sol–gel transition takes place between 32–35 °C, which is optimally below the temperature of the nasal cavity in a quick manner below 5 min, a suitable strategic criterion against the mucociliary clearance. In vitro drug release and permeability studies confirmed a rapid kinetics in the case of the encapsulated dexamethasone accompanied with a sustained release of tobramycin, as the hydrophilic drug.

Microneedle arrays (MNAs) consist of a few dozens of submillimeter needles, which tend to penetrate through the stratum corneum layer of the skin and deliver hardly penetrating drugs to the systemic circulation. The application of this smart dosage form shows several advantages, such as simple use and negligible pain caused by needle punctures compared to conventional subcutaneous injections. Dissolving MNAs (DMNAs) represent a promising form of cutaneous drug delivery due to their high drug content, biocompatibility, and ease of use. Although different technologies are suitable to produce microneedle arrays (e.g., micromilling, chemical etching, laser ablation etc.), many of these are expensive or hardly accessible. Following the exponential growth of the 3D-printing industry in the last decade, high-resolution desktop printers became accessible for researchers to easily and cost-effectively design and produce microstructures, including MNAs. In this work, a low force stereolithography (LFS) 3D-printer was used to develop the dimensionally correct MNA masters for the spin-casting method. The present study aimed to develop and characterize drug-loaded DMNAs using a two-level, full factorial design for three factors focusing on the optimization of DMNA production and adequate drug content. For the preparation of DMNAs, carboxymethylcellulose and trehalose were used in certain amounts as matrices for dexamethasone sodium phosphate (DEX). Investigation of the produced DexDMNAs included mechanical analysis via texture analyzer and optical microscopy, determination of drug content and distribution with HPLC and Raman microscopy, dissolution studies via HPLC, and ex vivo qualitative permeation studies by Raman mapping. It can be concluded that a DEX-containing, mechanically stable, biodegradable DexDMNA system was successfully developed in two dosage strengths, of which both efficiently delivered the drug to the lower layers (dermis) of human skin. Moreover, the ex vivo skin penetration results support that the application of DMNAs for cutaneous drug delivery can be more effective than that of a conventional dermal gel.

Abstract Ascorbic acid (AA) has a pivotal role in corneal wound healing via stimulating the biosynthesis of highly organized extracellular matrix components, but its rapid degradation and low corneal permeability limits its therapeutic effects. In this paper, we present the pharmacokinetic properties of a liposomal-based formulation of AA in terms of corneal permeation. Chemical stability, shelf-life, and drug release rate of lyophilized liposome (AA-LLipo) formulation was determined in comparison to free-form of AA solution using high-performance liquid chromatography (HPLC) and rapid equilibrium dialysis. In vitro transcorneal permeability was studied using a parallel artificial membrane permeability assay (PAMPA). Ex vivo permeation was examined on AA-LLipo-treated porcine cornea by determining the AA content on the ocular surface, in the cornea as well as in the aqueous humor using HPLC, and by Raman-mapping visualizing the AA-distribution. Our results showed that the liposomal formulation improved the chemical stability of AA, while drug release was observed with the same kinetic efficiency as from the free-form of AA solution. Both corneal-PAMPA and porcine corneal permeability studies showed that AA-LLipo markedly improved the corneal absorption kinetics of AA, thus, increasing the AA content in the cornea and aqueous humor. AA-LLipo formulation could potentially increase the bioavailability of AA in corneal tissues.

Medicated foams have emerged as promising alternatives to traditional carrier systems in pharmaceutical research. Their rapid and convenient application allows for effective treatment of extensive or hirsute areas, as well as sensitive or inflamed skin surfaces. Foams possess excellent spreading capabilities on the skin, ensuring immediate drug absorption without the need for intense rubbing. Our research focuses on the comparison of physicochemical and biopharmaceutical properties of three drug delivery systems: foam, the foam bulk liquid, and a conventional hydrogel. During the development of the composition, widely used diclofenac sodium was employed. The safety of the formulae was confirmed through an in vitro cytotoxicity assay. Subsequently, the closed Franz diffusion cell was used to determine drug release and permeation in vitro. Ex vivo Raman spectroscopy was employed to investigate the presence of diclofenac sodium in various skin layers. The obtained results of the foam were compared to the bulk liquid and to a conventional hydrogel. In terms of drug release, the foam showed a rapid release, with 80% of diclofenac released within 30 min. In summary, the investigated foam holds promising potential as an alternative to traditional dermal carrier systems, offering faster drug release and permeation.

This study focuses on how to define an Analytical Target Profile (ATP) which is intended for use in practice and on facilitating the selection of in vitro release test (IVRT) technology for diclofenac sodium topical hydrogel and cream. The implementation involves incorporating the new draft guidelines of the International Council for Harmonisation (ICH Q14) and USP (United States Pharmacopeia) Chapter 1220. Four IVRT apparatuses were compared (USP Apparatus II with immersion cell, USP Apparatus IV with semisolid adapter, static vertical diffusion cell, and a new, in-house-developed flow-through diffusion cell) with the help of the ATP. Performance characteristics such as accuracy, precision, cumulative amount released at the end of the IVRT experiment, and robustness were investigated. We found that the best apparatus for developing IVRT quality control (QC) tests in both cases was USP II with an immersion cell. All four different IVRT apparatuses were compared with each other and with the data found in the literature.

In this present formulation study, vinpocetine-loaded nano-spray-dried polymeric micelles were developed via nano-spray-drying. Three different mucoadhesive excipients were applied in the studies, namely chitosan, hyaluronic acid and hydroxypropyl methylcellulose. In all cases, the formulations had a proper particle size and drug content after drying with spherical morphology and amorphous structure. After rapid dissolution in water, the polymeric micelles had a particle size around 100–130 nm, in monodisperse size distribution. The high encapsulation efficiency (>80%) and high solubilization (approx. 300-fold increase in thermodynamic solubility) contributed to rapid drug release (>80% in the first 15 min) and fast passive diffusion at simulated nasal conditions. The formulated prototype preparations fulfilled the demands of a low-viscosity, moderately mucoadhesive nasal drug delivery system, which may be capable of increasing the overall bioavailability of drugs administered via the auspicious nasal drug delivery route.

Abstract Background Cystic fibrosis (CF) is a life-threatening multiorgan genetic disease, particularly affecting the lungs, where recurrent infections are the main cause of reduced life expectancy. In CF, mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein impair transepithelial electrolyte and water transport, resulting in airway dehydration, and a thickening of the mucus associated with abnormal viscoelastic properties. Our aim was to develop a rheological method to assess the effects of hypertonic saline (NaCl) and NaHCO3 on CF sputum viscoelasticity in vitro, and to identify the critical steps in sample preparation and in the rheological measurements. Methods Sputum samples were mixed with hypertonic salt solutions in vitro in a ratio of either 10:4 or 10:1. Distilled water was applied as a reference treatment. The rheological properties of sputum from CF patients, and the effects of these in vitro treatments, were studied with a rheometer at constant frequency and strain, followed by frequency sweep tests, where storage modulus (G′), loss modulus (G″) and loss factor were determined. Results We identified three distinct categories of sputum: (i) highly elastic (G′ > 100,000 Pa), (ii) elastic (100,000 Pa > G′ > 1000 Pa), and (iii) viscoelastic (G′

Antiseptics – besides mechanical debridement – have an important role in the treatment of destructive periodontitis. Subgingival drug delivery systems containing chlorhexidine gluconate (CHX) may enhance or be a substitute to non-surgical therapy. In this article, we investigate a CHX-containing drug delivery system which is solid at room temperature but softens at body temperature. The examination was focused on the hardness, the drug diffusion profile and the antimicrobial effectiveness of the formulation. Hardness was analyzed with a texture analyzer equipped with a spherical probe 5 mm in diameter. The investigation was carried out at 25 and 37 °C. The drug diffusion from formulations was investigated for one week in PBS solution. The antimicrobial effectiveness of the delivery systems was analyzed on 6 different anaerobic bacterial strains. Results show that hardness of formulations at 25 °C is around 2000 mN which is suitable for handling and insertion, whereas at 37 °C in PBS solution, hardness decreases greatly (to 800 mN) which contributes to the accommodation of the delivery systems to the shape of the periodontal pocket, the penetration of gingival crevicular fluid and the drug diffusion from formulations. Results of the drug diffusion study indicate that 50% of the CHX diffused from the formulations during the one-week period and a concentration of 8 μg/mL were maintained in the acceptor phase after 24 hours. Formulations effectively inhibited the growth of anaerobic bacteria for at least one week and showed similar effectiveness to formulations containing amoxicillin or the combination of metronidazole and zinc hyaluronate. Our results suggest that this delivery system alone or in combination with mechanical debridement may be effective in the treatment of periodontitis.

The application of enzyme-based therapies has received significant attention in modern drug development. Lipases are one of the most versatile enzymes that can be used as therapeutic agents in basic skin care and medical treatment related to excessive sebum production, acne, and inflammation. The traditional formulations available for skin treatment, such as creams, ointments or gels, are widely applied; however, their use is not always accompanied by good drug penetration properties, stability, or patient adherence. Nanoformulated drugs offer the possibility of combining enzymatic and small molecule formulations, making them a new and exciting alternative in this field. In this study polymeric nanofibrous matrices made of polyvinylpyrrolidone and polylactic acid were developed, entrapping lipases from Candida rugosa and Rizomucor miehei and antibiotic compound nadifloxacin. The effect of the type of polymers and lipases were investigated, and the nanofiber formation process was optimized to provide a promising alternative in topical treatment. Our experiments have shown that entrapment by electrospinning induced two orders of magnitude increase in the specific enzyme activity of lipases. Permeability investigations indicated that all lipase-loaded nanofibrous masks were capable of delivering nadifloxacin to the human epidermis, confirming the viability of electrospinning as a formulation method for topical skin medications.

A two-component injectable hydrogel was suitably prepared for the encapsulation and prolonged release of tilorone which is an antimuscular atrophy drug. The rapid (7–45 s, depending on the polymer concentration) in situ solidifications of the hydrogel were evoked by the evolving Schiff-base bonds between the aldehyde groups of modified PVA (4-formyl benzoate PVA, PVA-CHO, 5.9 mol% functionalization degree) and the amino groups of 3-mercaptopropionate chitosan (CHIT-SH). The successful modification of the initial polymers was confirmed by both FTIR and NMR measurements; moreover, a new peak appeared in the FTIR spectrum of the 10% w/v PVA-CHO/CHIT-SH hydrogel at 1647 cm−1, indicating the formation of a Schiff base (–CH=N–) and confirming the interaction between the NH2 groups of CHIT–SH and the CHO groups of PVA-CHO for the formation of the dynamic hydrogel. The reaction between the NH2 and CHO groups of the modified biopolymers resulted in a significant increase in the hydrogel’s viscosity which was more than one thousand times greater (9800 mPa·s) than that of the used polymer solutions, which have a viscosity of only 4.6 and 5.8 mPa·s, respectively. Furthermore, the initial chitosan was modified with mercaptopropionic acid (thiol content = 201.85 ± 12 µmol/g) to increase the mucoadhesive properties of the hydrogel. The thiolated chitosan showed a significant increase (~600 mN/mm) in adhesion to the pig intestinal membrane compared to the initial one (~300 mN/mm). The in vitro release of tilorone from the hydrogel was controlled with the crosslinking density/concentration of the hydrogel; the 10% w/v PVA-CHO/CHIT-SH hydrogel had the slowest releasing (21.7 h−1/2) rate, while the 2% w/v PVA-CHO/CHIT-SH hydrogel had the fastest releasing rate (34.6 h−1/2). Due to the characteristics of these hydrogels, their future uses include tissue regeneration scaffolds, wound dressings for skin injuries, and injectable or in situ forming drug delivery systems. Eventually, we hope that the developed hydrogel will be useful in the local treatment of muscle atrophy, such as laryngotracheal atrophy.

A high dose of amoxicillin is recommended as the first-line therapy for acute bacterial rhinosinusitis (ABR). However, oral administration of amoxicillin is connected to many adverse reactions coupled with moderate bioavailability (~60%). Therefore, this study aimed to develop a topical nasal preparation of amoxicillin, employing a thermoresponsive nanogel system to increase nasal residence time and prolong drug release. Rheological investigations revealed that formulations containing 21–23% w/w Poloxamer 407 (P407) were in accordance with the requirement of nasal administration (gelling temperature ~35 °C). The average hydrodynamic diameter (w/w P407 could be considered as an optimized concentration for effective nasal delivery. Antibacterial activity studies showed that the ability of amoxicillin-loaded in situ gelling nasal nanogel to inhibit bacterial growth (five common ABR pathogens) preserved its effectiveness in comparison to 1 mg/mL amoxicillin aqueous solution as a positive control. Altogether, the developed amoxicillin-loaded in situ gelling thermoresponsive nasal nanogel can be a potential candidate for local antibiotic therapy in the nasal cavity.

Poor bioavailability of eye drops is a well-known issue, which can be improved by increasing the residence time on the eye surface and the penetration of the active pharmaceutical ingredient (API). This study aims to formulate in situ gelling mucoadhesive ophthalmic preparations. To increase the residence time, the formulations were based on a thermosensitive polymer (Poloxamer 407 (P407)) and were combined with two types of mucoadhesive polymers. Dexamethasone (DXM) was solubilized by complexation with cyclodextrins (CD). The effect of the composition on the gel structure, mucoadhesion, dissolution, and permeability was investigated with 33 full factorial design. These parameters of the gels were measured by rheological studies, tensile test, dialysis membrane diffusion, and in vitro permeability assay. The dissolution and permeability of the gels were also compared with DXM suspension and CD-DXM solution. The gelation is strongly determined by P407; however, the mucoadhesive polymers also influenced it. Mucoadhesion increased with the polymer concentration. The first phase of drug release was similar to that of the CD-DXM solution, then it became prolonged. The permeability of DXM was significantly improved. The factorial design helped to identify the most important factors, thereby facilitating the formulation of a suitable carrier for the CD-DXM complex.

Foams are increasingly popular in the field of dermatology due to their many advantages such as easy spreading, good skin sensation, and applicability in special skin conditions. One of the critical points of foam formulation is the choice of the appropriate stabilizing ingredients. One of the stability-increasing strategies is retarding the liquid drainage of liquid films from the foam structure. Therefore, our aim was the application of different hydrogel-forming polymers in order to retain the stabilizing liquid film. Dexpanthenol and niacinamide-containing foams were formulated, where xanthan gum and hyaluronic acid were used as foam-stabilizing polymers. Amplitude (LVE range) and frequency sweep (G’, G”, tanδ, and frequency dependency) were applied as structure- and stability-indicating rheological parameters. The rheological data were compared with the results of the cylinder method, microscopical images, and the spreadability measurements. The application of the gel-forming polymers increased the stability of the dermal foams (increased LVE range, G’ values, and decreased frequency dependency). These results were in correlation with the results of the cylinder and spreadability tests. It was concluded that in terms of both foam formation and stability, the combination of xanthan gum and dexpanthenol can be ideal.

The aim of our study was to adapt the analytical quality by design (AQbD) approach to design an effective in vitro release test method using USP apparatus IV with a semi-solid adapter (SSA) for diclofenac sodium hydrogel. The analytical target profile (ATP) of the in vitro release test and ultra-high-performance liquid chromatography were defined; the critical method attributes (CMAs) (min. 70% of the drug should be released during the test, six time points should be obtained in the linear portion of the drug release profile, and the relative standard deviation of the released drug should not be over 10%) were selected. An initial risk assessment was carried out, in which the CMAs (ionic strength, the pH of the media, membrane type, the rate of flow, the volume of the SSA (sample amount), the individual flow rate of cells, drug concentration %, and the composition of the product) were identified. With the results, it was possible to determine the high-risk parameters of the in vitro drug release studies performed with the USP apparatus IV with SSA, which were the pH of the medium and the sample weight of the product. Focusing on these parameters, we developed a test protocol for our hydrogel system.

In recent years, the study of dermal preparations has received increased attention. There are more and more modern approaches to evaluate transdermal formulations, which are crucial in proving the efficacy of a formulation. The aim of this study was to compare permeation across innovative synthetic membranes (Strat-M and Skin PAMPA membranes) and heat-separated human epidermis (HSE, gold standard membrane) using four different dermal formulations. The Strat-M and Skin PAMPA membranes were designed to mimic the stratum corneum layer of the human epidermis. There have also been some publications on their use in dermal formulation development, but further information is needed. Drug permeation was measured using formulations containing diclofenac sodium (two hydrogels and two creams). The HSE, Strat-M, and Skin PAMPA membranes proved to be significantly different, but based on the results, the Strat-M membrane showed the greatest similarity to HSE. The permeation data of the different formulations across different membranes showed good correlations with formulations similar to these four, which allows the prediction of permeation across HSE using these synthetic membranes. In addition, Strat-M and Skin PAMPA membranes have the potential to select and differentiate a dermal formulation containing diclofenac sodium as an early screening model.

Fibers were spun from a mixture of dichloromethane (DCM) and dimethyl sulfoxide (DMSO) solution of poly(lactic acid)(PLA) containing various amounts of amoxicillin (Amox) as the active component. Composition changes during spinning, structure, solubility, and the location of the drug were considered during the evaluation of drug release and microbial activity. The results showed that the composition of the material changes during the preparation procedure. The solubility of the drug in the components and that of the components in each other is limited, which results in the formation of several phases and the precipitation of the drug. The technology used results in the partitioning of the drug; some is located inside, while the rest is among the fibers. The wetting of the fibers or disks by the water-based dissolution media is poor, the penetration of the liquid into and the diffusion of the active component out of the device takes considerable time. Drug release takes place in one, burst-like step, only Amox located among the fibers dissolve and diffuse into the surrounding medium. The slow second stage of release claimed in the literature is less probable because the size of the Amox molecule is considerably larger than the holes creating the free volume of the polymer. The prepared device has antimicrobial activity, inhibits the growth of the two bacterial strains studied. The time scale of activity is short and corresponds to that of the release experiments and the burst-like behavior of the device. The results clearly prove that physical–chemical factors play a determining role in the effect and efficiency of medical devices prepared from electrospun fibers containing an active component.

The aim of this study was to investigate whether and how the biological media which are in contact with silicone oil play a role in the silicone emulsification process. Commercially available Oxane 1300 silicone oil and potential hydrophilic phases of the emulsions in the eye (porcine aqueous humor, porcine vitreous and balanced salt solution) were investigated separately and in a mixture or emulsions by means of surface tension, rheological, zeta potential measurements and microscopic investigation. The surface tension of biological media (vitreous and aqueous humor) was significantly lower than that of non-biological media, especially in the case of aqueous humor, which indicates a remarkable emulsification tendency with these phases. The biological media are able to form both oil-in-water and water-in-oil emulsions, which can be observed in the clinical practice as well. It was established that the vitreous has a more expressed emulsification ability compared with the aqueous humor because smaller and more stable droplets can form with silicon oil when the vitreous is still there. It can be concluded that the vitreous has a higher impact on emulsification than the aqueous medium, which can predict that the vitreous remaining after vitrectomy has a key role in emulsion formation in the eye with silicone oil endotamponade.

The aim of this study was to develop an intranasal in situ thermo-gelling meloxicam-human serum albumin (MEL-HSA) nanoparticulate formulation applying poloxamer 407 (P407), which can be administered in liquid state into the nostril, and to increase the resistance of the formulation against mucociliary clearance by sol-gel transition on the nasal mucosa, as well as to improve drug absorption. Nanoparticle characterization showed that formulations containing 12–15% w/w P407 met the requirements of intranasal administration. The Z-average (in the range of 180–304 nm), the narrow polydispersity index (PdI, from 0.193 to 0.328), the zeta potential (between −9.4 and −7.0 mV) and the hypotonic osmolality (200–278 mOsmol/L) of MEL-HSA nanoparticles predict enhanced drug absorption through the nasal mucosa. Based on the rheological, muco-adhesion, drug release and permeability studies, the 14% w/w P407 containing formulation (MEL-HSA-P14%) was considered as the optimized formulation, which allows enhanced permeability of MEL through blood–brain barrier-specific lipid fraction. Cell line studies showed no cell damage after 1-h treatment with MEL-HSA-P14% on RPMI 2650 human endothelial cells’ moreover, enhanced permeation (four-fold) of MEL from MEL-HSA-P14% was observed in comparison to pure MEL. Overall, MEL-HSA-P14% can be promising for overcoming the challenges of nasal drug delivery.

Semisolid dosage forms are recommended for the dermal care of babies and children. If we look at the ingredients of these preparations, there are still many cases in which there are substances (occlusive agents, preservatives) that no longer meet certain requirements of the modern age, so it is timely to replace them with other substances. The aim of this work was to formulate a science-based formulation with new components that keep or improve its moisturizing properties, rheological parameters, and microbiological stability. Occlusive oils, like white petrolatum and liquid paraffin and the preservative parabens are traditional ingredients in oil in water creams, were replaced with white beeswax, sunflower oil, and phenoxyethanol, respectively. Cocoa butter, urea, and glycerol were added to improve long-lasting hydration and support the barrier function of the reformulated creams. The rheological properties of the formulations were determined. The effects of the preparations on skin hydration and on the barrier function of the skin were tested. Furthermore, microbiological stability was investigated. The result of the reformulation was an o/w cream that provided a good longer-lasting hydration effect; supported the barrier function of the baby skin without occlusion; and had adequate consistency, easy spreading, a pleasant skin feeling, proper pH, and good microbiological stability.

The human skin is marked as a standard by the regulatory agencies in the permeation study of dermal formulations. Artificial membranes can substitute human skin to some extent. Academicians and pharmaceutical corporations are focusing their efforts on developing standardized protocols and safe, reliable options to substitute human skin for carrying out permeability studies. Our research aim was to study the applicability of new techniques in the case of different types of dermal formulations. The skin parallel artificial membrane permeability assay (PAMPA) method and Raman mapping were compared to the gold-standard Franz cell method. A hydrogel and two types of creams were investigated as the most generally used dermal preparations. The values of the diffused drug were closer to each other in PAMPA and Franz cell measurement. The diffused amount of drug showed the same order for the different formulations. These results correlate well with the results of Raman mapping. Our conclusions suggest that all early screening examinations can be performed with model tools such as skin PAMPA supplemented with methods like Raman mapping as a semi-quantitative method.

Generally, topically applied eye drops have low bioavailability due to short residence time and low penetration of the drug. The aim of the present study was to incorporate dexamethasone (DXM) into nano lipid carriers (NLC), which contain mucoadhesive polymer, in order to increase the bioavailability of the drug. A 23 factorial experimental design was applied, in which the three factors were the polymer, the DXM, and the emulsifier concentrations. The samples were analyzed for particle size, zeta potential, polydispersity index, and Span value. The significant factors were identified. The biocompatibility of the formulations was evaluated with human corneal toxicity tests and immunoassay analysis. The possible increase in bioavailability was analyzed by means of mucoadhesivity, in vitro drug diffusion, and different penetration tests, such as in vitro cornea PAMPA model, human corneal cell penetration, and ex vivo porcine corneal penetration using Raman mapping. The results indicated that DXM can be incorporated in stable mucoadhesive NLC systems, which are non-toxic and do not have any harmful effect on cell junctions. Mucoadhesive NLCs can create a depot on the surface of the cornea, which can predict improved bioavailability.

Dermal and transdermal drug therapy is increasing in importance nowadays in drug development. To completely utilize the potential of this administration route, it is necessary to optimize the drug release and skin penetration measurements. This review covers the most well-known and up-to-date methods for evaluating the cutaneous penetration of drugs in vitro as a supporting tool for pharmaceutical research scientists in the early stage of drug development. The aim of this article is to present various experimental models used in dermal/transdermal research and summarize the novel knowledge about the main in vitro methods available to study skin penetration. These techniques are: Diffusion cell, skin-PAMPA, tape stripping, two-photon microscopy, confocal laser scanning microscopy, and confocal Raman microscopic method.

The aim of this research was to investigate the stability of a lidocaine-loaded nanostructured lipid carrier dispersion at different temperatures, formulate a nanostructured lipid carrier gel, and test the penetration profile of lidocaine from the nanostructured lipid carrier gel using different skin penetration modeling methods. The formulations were characterized by laser diffraction, rheological measurements and microscopic examinations. Various in vitro methods were used to study drug release, diffusion and penetration. Two types of vertical Franz diffusion cells with three different membranes, including cellulose, Strat-M®, and heat separated human epidermis were used and compared to the Skin-parallel artificial membrane permeability assay (PAMPA) method. Results indicated that the nanostructured lipid carrier dispersion had to be gelified as soon as possible for proper stability. Both the Skin-PAMPA model and Strat-M® membranes correlated favorably with heat separated human epidermis in this research, with the Strat-M® membranes sharing the most similar drug permeability profile to an ex vivo human skin model. Our experimental findings suggest that even when the best available in vitro experiment is selected for modeling human skin penetration to study nanostructured lipid carrier gel systems, relevant in vitro/in vivo correlation should be made to calculate the drug release/permeation in vivo. Future investigations in this field are still needed to demonstrate the influence of membranes and equipment from other classes on other drug candidates.

Background: Despite being a highly prevalent disease and a possible contributor to adult tooth loss, periodontitis possesses no well-established therapy. The aim of the recent study was the development and evaluation of a mucoadhesive monophase lipid formulation for the sustained local delivery of amoxicillin, metronidazole, and/or zinc hyaluronate or gluconate. Methods: To investigate our formulations, differential scanning calorimetry, X-ray diffraction, swelling, erosion, mucoadhesivity, drug release, and antimicrobial measurements were performed. Results: Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) results show that the loaded drugs are in a suspended form, the softening of the formulations starts at body temperature, but a part remains solid, providing sustained release. Swelling of the lipid compositions is affected by the hydrophilic components, their concentration, and the strength of the coherent lipid structure, while their erosion is impacted by the emulsification of melted lipid components. Conclusions: Results of drug release and antimicrobial effectiveness measurements show that a sustained release may be obtained. Amoxicillin had higher effectiveness against oral pathogens than metronidazole or zinc hyaluronate alone, but the combination of the two latter could provide similar effectiveness to amoxicillin. The applied mucoadhesive polymer may affect adhesivity, drug release through the swelling mechanism, and antimicrobial effect as well.

Dry eye disease is a relatively common ocular problem, which causes eye discomfort and visual disorders leading to a decrease in the quality of life. The aim of this study was to find a possible excipient for eye drop formulations, which is able to stabilize the tear film. A cationic thiolated polyaspartamide polymer, poly[(N-mercaptoethylaspartamide)-co-(N-(N′,N′-dimethylaminoethyl)aspartamide)] (ThioPASP-DME), was used as a potential vehicle. Besides satisfying the basic requirements, the chemical structure of ThioPASP-DME is similar to those of ocular mucins as it is a protein-like polymer bearing a considerable number of thiol groups. The solution of the polymer is therefore able to mimic the physiological properties of the mucins and it can interact with the mucus layer via disulphide bond formation. The resultant mucoadhesion provides a prolonged residence time and ensures protective effect for the corneal/conjunctival epithelium. ThioPASP-DME also has an antioxidant effect due to the presence of the thiol groups. The applicability of ThioPASP-DME as a potential excipient in eye drops was determined by means of ocular compatibility tests and through examinations of the interactions with the mucosal surface. The results indicate that ThioPASP-DME can serve as a potential eye drop excipient for the therapy of dry eye disease.