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The prime objective behind this investigation was to plan a Letrozole enclosed adhesive transdermal patch; since the transdermal route is an outright attractive option concerning its route, convenience and safety. Letrozole, a non-steroidal type II aromatase inhibitor, is reported for treating breast tumours and in postmenopausal women. In this study, few factors confined to formulation such as drug-in-adhesive, enhancers and amount of drug-loaded were investigated. The procedure used supposedly involves, the incarnation of the LET in phospholipids exploiting to a spray dryer. FTIR, X-RD, and DSC techniques which are used to evaluate entrapment efficiency were employed to LET spray-dried powder (LT-SDP). The molecule size, polydispersity file, and the EE were allegedly found to be 284.0 nm, 0.247 and 59.08%. On adding LT-SDP to a cream base with peppermint and olive oil as regular infiltration, the optimized formulation showed superior skin targeting in both in vitro and in vivo observations post-study.In vivo bioavailability studies showed just about four-fold increment in the plasma whereas the mean residence time and half-life were reasonably higher as compared to the LET cream in plain. The in vivo results observed remarkable patch concurrence with the plasma fixations anticipated from the in vitro infiltration. As an outpatient convenience, avoidance of gastrointestinal incompatibility provides suitability for self-administration for breast cancer prevention and treatment.

Polymers are used in drug delivery devices for drug encapsulation and release. Natural polymers often have advantages such as biocompatibility, biodegradability and biologically recognizable moieties which support cellular activities, compared to synthetic polymers. Chitosan, a naturally occurring polysaccharide obtained from chitin, has recently drawn attention because chitosan is non-toxic, biocompatible, biodegradable, stable and sterilizable. The additional qualities of chitosan are the release rate of drug, easy modification, cross-linking ability with other polymers, antimicrobial properties, gel forming ability, bioadhesion, immunostimulation, activation of macrophages and gas permeability. Here, I review applications of chitosan in drug delivery. The properties of chitin and chitosan, and the mechanisms of drug release are also presented.

The key objective of the current research was to fabricate and optimize Capecitabine (Cap)-loaded [poly(lactic-co-glycolic acid)] PLGA-based nanoparticles (NPs) by enabling quality by design (QbD) approach for enhancing antitumor activity by promising delivery of the drug at the colonic site. The current research was based on fabricating PLGA-based nanoparticles along with Eudragit S100 as enteric polymer employing solvent shifting method followed by optimization using QbD approach. This approach was found to be useful for understanding the multiple factors and their interaction influencing the product by utilizing Design of Experiment (DOE). Box-Behnken design (BBD) was adopted to achieve the required critical quality attributes (CQAs), i.e., minimizing particle size, maximizing entrapment efficiency, and minimizing PDI value. The optimized nanoparticles were lyophilized and characterized by FT-IR, DSC, TEM, DLS, MTT assay using HT-29 cell lines, and in vivo pharmacokinetic studies. The optimized PLGA-based nanoparticles were found to possess average particle size, PDI, zeta potential, and entrapment efficiency of 195 nm, 0.214, -6.65 mV, and 65%, respectively. TEM analysis revealed the spherical nature of nanoparticles. The FT-IR and DSC studies revealed no interaction. The bioavailability of Cap-loaded nanoparticles was found to be two fold increased than the pure drug, and also, it exhibited significantly more cytotoxic to tumor cells as compared to pure drug as confirmed by MTT assay. The optimized PLGA-based nanoparticles found to possess enhanced bioavailability and significantly more cytotoxic potential as compared to pure drug.

The materials accomplished with both biodegradable and renewable properties are called “green” materials. The biodegradable property can solve the problem related to environment such as pollution, whereas renewable property can be exploited for sustainability. Many synthetic polymers are being widely used in many industrial sectors for various purposes. However, many of them are nonbiodegradable in nature, which are impacting our environment. Therefore they are being replaced with biodegradable polymers. Among many natural and synthetic biodegradable polymers, poly(vinyl alcohol) (PVA) attracted huge attention because of its important desired qualities such as biodegradable, biocompatible, water solubility, nontoxic, and noncarcinogenic. In addition, it can exist in both crystalline and amorphous form. Due to earlier qualities, it can be used in the fabrication of different forms of green materials such as hydrogel, films, scaffold, membranes, fibers, particulate systems, and composites. In this chapter, various fabrication techniques of earlier forms of PVA and their characterization are described.

Dosage forms are defined as the systems comprised of one or more active ingredients in association with inert excipients (additives) that constitute the vehicle or formulation matrix. These additives are usually incorporated in the formulation to enhance physical appearance (aesthetic value), facilitate handling, improve stability and potentially influence the absorption and/or bioavailability of the active ingredients. In this context, pharmaceutical semisolid dosage forms including ointment, cream and gels contain one or more medicaments dissolved in or dispersed in a suitable base and appropriate excipients such as emulsifier, gelling agent, viscosity modifiers, antimicrobial agents, antioxidants and or stabilizing agents. These conventional forms of semisolids are meant for delivering drugs into skin and body cavities. But, the recent development in semisolid dosage forms is mainly oriented towards the systemic circulation and more particularly site-specific delivery of drug in an amount, which can elicit therapeutic action. Therefore, this chapter focuses on recent advances in semisolid dosage forms to enhance their aesthetic value and to increase the drug permeation across the skin without impacting their stability, including micro- and nanoemulsion (NE) systems, bioadhesive/mucoadhesive gel, in situ gels (e.g., thermal gel), in situ injectable gels, semisolid containing vesicular systems (e.g., liposomes, ethosomes, niosomes, proniosomes, ethosomesand transfersomes, and 126particulate systems (such as polymeric micro- and nanoparticles, lipid-based particles), cryogels, and pluronic lecithin organogels (PLO). This article also discusses the theory of semisolids, new tools available for the evaluation of semisolids. Furthermore, regulatory requirements for the semisolid dosage forms are also described in this chapter.

The main objective of the present investigation was to develop transdermal films of ondansetron HCl (OS) with polyvinyl alcohol (PVA) using Box-Behnken design and to optimize them employing Derringer’s optimization tool. Design-Expert software was used to investigate the effect of independent variables such as concentration (%, w/w) of glycerol and 1,8-cineole, and number of Freeze-Thaw cycle (F-T cycle) on the dependent variables viz. ultimate tensile strength (UTS) and flux. The F-T cycle followed by solvent casting method was employed to develop films. Universal tensile testing machine and Franz diffusion cell were used to measure tensile strength and flux, respectively. Quadratic model was found to be best fit model and the effect of concentration of glycerol and the number of F-T cycle significantly influences the tensile strength (p

The transdermal drug-in-adhesive (DIA) patch of simvastatin (SM) was developed using acrylic adhesives such as DURO-TAK® 87-9301, DURO-TAK® 87-4287, DURO-TAK® 87-235A. The patches were evaluated for in vitro drug permeation across the pork ear skin using diffusion cell and stability studies. Among the three acrylic adhesives used, DURO-TAK® 87-9301 exhibited maximum flux (5.18 ± 0.23 µg/cm2/h). To further enhance the drug permeation, isopropyl myristate (IPM), d -limonene and 1,8-cineol as penetration enhancers (PEs) were incorporated into the DIA patch prepared from DURO-TAK® 87-9301. Out of those, IPM containing patch exhibited a flux of 16.45 ± 1.67 µg/cm2/h revealing that IPM is the best PE. The stability study was carried out on optimized fresh (SA4) and 6 months old patches stored at room and at accelerated condition (40 ± 2 °C/75 ± 5%RH) using FTIR, DSC and SEM techniques. Significant shift of peaks were not observed in FTIR spectra and DSC thermograms of the patches after the stability period. SEM micrographs of patches did not show any evidence of recrystallization indicating the presence of drug in the molecular form throughout the adhesive matrix. The investigation reveals that the DIA patch studied as above is stable and may serve as a potential drug delivery system for simvastatin.

The present investigation is focused on the development of transdermal film-forming gel (FFG) loaded with etoricoxib employing research surface methodology (RSM). Box-Behnken surface design method was used to develop experimental run using different concentrations of etoricoxib, hydroxypropyl methylcellulose (HPMC K100M), and eudragit RL100 as independent variables, and Derringer's optimization tool was employed to optimize best possible formulation. The dependent variables considered in this study were viscosity and drug permeation at 24 h (Q24, μg/cm2). Anti-inflammatory study was performed on Wistar albino rats for 8 h. Skin irritation studies and accelerated stability studies were performed for validated FFG formulations. Quadratic model was found to be best fit model (p < 0.0001) for both the responses. The influence of HPMC concentration on the viscosity was found to be highest whereas concentration of etoricoxib was maximum for Q24. The optimum composition of the FFG was observed to be 4% of etoricoxib, 1.1246% of HPMC, and 0.4% of eudragit. Above composition resulted in viscosity of 1549.5 mPa.s and maximum Q24 of 4639.11 μg/cm2 with desirability 0.918. The in vivo anti-inflammatory study demonstrated better sustained release effect (for 8 h) of optimized FFG compared to orally administered drug suspension. An average irritation score of 0.555 was observed on Draize scoring system. The validated FFG formulation was found to be stable for the 3 months in accelerated conditions. It can be concluded from the above investigations that the validated FFG formulation of etoricoxib is well tolerated and could provide sustained drug release for 8 h. Graphical abstract.

The aim of the present investigation was to prepare and optimize suitable combination of polymers hydroxypropyl methylcellulose (HPMC) and pluronic ® F127 (PN F127) for the development of thermosensitive gel of Metoprolol succinate (MS) using central composite design (CCD). The effect of formulation factors (concentration of HPMC and PN F127) on responses such as cumulative percentage release (CPR) of MS, bioadhesive force (BF) and viscosity was measured statistically. Quadratic model was found to be best fit model among different models used in the study. The optimum conditions were found to be 0.92% of HPMC and 15% of PN F127. Under these conditions, the predicted CPR, BF and viscosity were found to be 84.94 μg/cm 2 , 41.56 gf and 48.94 Pa s, respectively. Ex vivo permeation of MS from optimized thermosensitive gel across abdominal skin of rat demonstrated highest flux (64.35 μg/cm 2 /h) for the gel formulation containing 1,8-cineole (5% w/w). The hypotensive activity was performed on normotensive rabbits and the results showed that the optimized formulation prolonged the activity up to 12 h. The above findings indicated that thermosensitive gel of MS for skin application exhibited strong potential against hypertension and expected to provide a better alternative to oral MS formulations.

Polymers are major components of drug delivery systems in terms of drug encapsulation and release. Natural polymers offer advantages such as biocompatibility, biodegradability and biologically-recognizable moieties, which support cellular activities, compared to synthetic polymers. Chitosan, a naturally-occurring polysaccharide obtained from chitin, has drawn much attention in the pharmaceutical field because chitosan possess valuable properties such as non-toxic, biocompatibile, biodegradable, stable and sterilizable. The additional qualities of chitosan such as controlling the release rate of drug, scope for modification, cross-linking ability with other polymers, antimicrobial properties, gel forming ability, bioadhesion, immunostimulation, activation of macrophages, and gas permeability, make chitosan one of the most versatile co-polymer for drug delivery. This chapter discusses applications of chitosan in drug delivery, along with drug delivery systems that can be developed based on chitosan. Furthermore, the properties of chitin and chitosan and the mechanisms of drug release from chitosan-based drug delivery systems are presented.

In the present study, pluronic lecithin organogel (PLO) of diltiazem hydrochloride (DZH) was developed by taking different ratios of organic phase to aqueous phase (1:3, 1:4, and 1:5) with varying concentration of soya lecithin (20, 30, and 40 % w/w) in organic phase (isopropyl myristate, IPM) and pluronic (20, 25, and 30 % w/w) in aqueous phase, respectively, and characterized for in vitro parameters and ex vivo permeation study. The results of in vitro parameters were found to be within permissible limit and all the PLOs were physically stable at refrigeration and ambient temperature. The influence of phase ratio and different concentrations of soya lecithin on DZH release from the PLOs was found to be significant (p

Nanocomposites, nanosized particles in polymer/metal/ceramic matrix, are one of the highly talked technological products on 21st century, which have lived up to the expectation. These are having high potential in almost all industrial sectors owing to their improved properties in terms of mechanical, thermal, optical, electrochemical, biodegradable, biocompatible, etc. In recent years, it has been widely used in delivery of drug through various routes. Transdermal route, where the drug molecules have to penetrate through the skin and reach to systemic circulation, is one of such routes in which nanocomposites have tremendous application potential. This chapter has focused mainly on the types of nanocomposites and their application in transdermal drug delivery (TDD) in the form of hydrogel, membranes and films, pressure-sensitive adhesives (PSA), and microneedles with examples. It also discussed the fundamentals of TDD.

The aim of the present research was to optimize cryogel formulation of Diltiazem hydrochloride (DZ) with poly(vinyl alcohol) (PVA) and hydroxypropyl methylcellulose (HPMC) by utilizing response surface methodology followed by ex vivo permeation study on the optimized gel containing penetration enhancers. A 3-level factorial design was employed to formulate the experimental runs and to evaluate the effect of two independent variables such as the concentration of PVA and HPMC on characteristics of cryogel such as bioadhesive strength (BS) and in vitro drug release (dependent variables). Response surface plots such as contour and 3D plots were generated by the Design Expert® software to analyze the effect of independent variables on dependent variables. Fourier transform infrared spectroscopy studies confirmed the absence of interaction between DZ and polymers. Among various models generated by the software, quadratic model was found to be best fit for both the responses. Both the formulation factors influenced BS synergistically. However, the effect of HPMC concentration was more pronounced compared to concentration of PVA. But, an opposite effect shown by both the formulation factors on cumulative percentage of drug release (CPR) in 8 h. The optimized batch of cryogel of DZ selected by the software was having composition of 5 % of PVA and 2 % of HPMC. Penetration enhancers such as 1,8-cineole, d-limonene and carvone were incorporated into the optimized gel and permeation study was carried out using abdominal skin of rat. The study demonstrated a highest flux of 118 ± 5.81 µg/cm2/h in case of 1,8-cineole containing gel followed by carvone and d-limonene.

In the current study Indomethacin (IM) fast dissolving tablets (FDTs) were prepared by direct compression technique in order to enhance its dissolution rate. The tablets were formulated using two different approaches; super-disintegration and efferves-cence. A combination formulation of above approaches was also developed to further improve its properties. The super-disintegrants used in the formulae were sodium starch glycolate (Primogel), cross-povidone (Kollidon) and cross-carmellose (Ac-di-sol). Sodium bicarbonate and citric acid combination was employed as effervescent ingredients. The prepared powder mixtures of IM were subjected to evaluation of various pre-compression parameters and tablets were evaluated for weight variation, dimension, hardness, friability, drug content, disintegration, wetting time, uniformity of dispersion, in vitro drug release and stability studies. The FT-IR spectra shown there are no interaction between of IM with excipient. The results of pre-compression studies indicate acceptable flow property for all the powder mixtures. The data of weight variation, dimension, hardness, friability, uniformity of dispersion and drug content studies were within the official limits. The wetting time and disintegration time decreases considerably with the increase in super-disintegrants amount. By using the combination approach, the disintegration and wetting time further decreased. In vitro dissolution studies were carried out using phosphate buffer pH 6.8 as dissolution medium for 60min and observed that formulation IF9, among super-disintegration approach, released highest percentage (97.13±2.09) of IM. In vitro drug release was highest (98.54±2.89) at 60 min for formulation IF11, when all the formulations were taken into consideration. The stability study was performed on the promised formulation IF11 at 40±2 o C/ 75±5% RH for 3 months and the results indicated that there were no significant changes in aforesaid tablet properties.

The use of topical formulation is popular over the past decade due to extensive researches made in the field of transdermal drug delivery. As a result, an increasing number of drugs are being added to the list of therapeutic agents that can be delivered to systemic circulation through the skin. Commonly available dosage forms for the topical application are creams, ointments, gels, patches etc. The therapeutic benefits of the above topical formulations are limited due to barrier property of stratum corneum (SC). The use of chemical penetration enhancers (CPEs) is one of the long standing approach to overcome the barrier property of SC. Numerous class of novel compounds have been evaluated for penetration enhancement activity, including soft enhancement for percutaneous absorption (SEPA), for example, 2 N-nonyl-1,3- dioxolanes, N-acetyle prolinate esters (such as pentyl- and octyl-N-acetyle prolinate), alkyldiloxanes (e.g., 1-Alkyl-3-b-D glucopyranosyl-1,1,3,3-tetramethyl disiloxanes), transcarbam (such as 5-(dodecyloxycarbonyl) pentylammonium-5- (dodecyloxycarbonyl) pentylcarbamate), iminosulfurane (like N-hexyl,N-benzoyl-S,S-dimethylimino-sulfuranes), capsaicin derivatives (e.g., Nonivamide), cinnamene compounds (such as cinnamic acid, cinnamaldehyde etc), terpenes (like clove and basil oil) and synergestic combination of penetration enhancers (SCOPE). We briefly describe about the anatomy of skin. Potential mechanisms of action of above novel PEs along with adverse reactions associated with traditional PEs are also considered in this review.

The present investigation focused on the development of Diltiazem HCl (DTH) matrix film and its characterization by in-vitro, ex-vivo and in-vivo methods. Films were prepared by solvent casting method by taking different ratios of hydroxypropyl methylcellulose K4M (HPMC K4M) and Eudragit RS100. Various parameters of the films were analyzed such as mechanical property using tensile tester, interaction study by Fourier transform infrared spectroscopy (FTIR) and Thermogravimetric analysis (TGA), in-vitro drug release through cellulose acetate membrane, ex-vivo permeation study using abdominal skin of rat employing Franz diffusion cell, and in-vivo antihypertensive activity using rabbit model. The FTIR studies confirmed the absence of interaction between DTH and selected polymers. Thermal analysis showed the shifting of endothermic peak of DTH in film, indicating the dispersion of DTH in molecular form throughout the film. Incorporation of 1,8-cineole showed highest flux (89.7 μg/cm(2)/h) of DTH compared to other penetration enhancers such as capsaicin, dimethyl sulfoxide (DMSO), and N-methyl pyrrolidone (NMP). Photomicrographs of histology study on optimized formulation (DF9) illustrated disruption of stratum corneum (SC) supporting the ex-vivo results. The in-vivo antihypertensive activity results demonstrated that formulation DF9 was effective in reducing arterial blood pressure in normotensive rabbits. SEM analysis of films kept for stability study (40 ± 2 °C/75% ± 5%RH for 3 months) revealed the formation of drug crystals which may be due to higher temperature. The findings of the study provide a better alternative dosage form of DTH for the effective treatment of hypertension with enhanced patient compliance.

Matrix type of simvastatin transdermal film (SSTF) was developed with poly(vinyl alcohol) (PVA) and eudragit RL100 (EG) using response surface methodology (RSM) to investigate combined effect of the selected process variables like SS concentration, PVA:EG ratio and the dibutyl phthalate (DBT) concentration at different levels on dependent variables such as tensile strength and flux, with an aim to optimize a suitable combination of drug, polymer and plasticizer ratio. The study reveals that the effect of DBT concentration was highest on tensile strength, while SS concentration exhibited pronounced effect on SS flux through the abdominal skin of rat. According to Derringer's desirability prediction tool, the composition of optimized film was found to be 2% of SS, 2:1 ratio of PVA:EG and 40% of DBT. Under these conditions, the SSTF exhibited a predicted value of tensile strength and flux of 11.871 MPa and 43.569 μg/cm(2)/h, respectively. The in vivo hypolipidemic study conducted for 14 days in hyperlipidemia induced Sprague-Dawley rats reveals that the optimized SSTF exhibited significant lowering of blood lipid level. The absence of skin irritation indicates that the prepared film was safe and well tolerated as transdermal formulation. Thus, the film may serve as an alternative therapy to oral dosage form of SS.

In the present scenario, most of the developed and new discovered drugs are posing real challenge to the formulation scientists due to their poor aqueous solubility which in turn is responsible for poor bioavailability. One of the approach to overcome above problem is the packaging of the drug in to particulate carrier system. Among various carriers, lipid emerged as very attractive candidate because of its unique property of enhancing the bioavailability of poorly water soluble drugs. Solid lipid, one of the physical forms of lipid, is used to formulate nanoparticles, popularly known as Solid lipid nanoparticles (SLNs), as an alternative carrier system to emulsions, liposomes and polymeric micro- and nano-particles. SLNs combine advantages of the traditional systems but avoid some of their major disadvantages. This paper reviews numerous production techniques for SLNs along with their advantages and disadvantages. Special attention is paid to the characterization of the SLNs by using various analytical tools. It also emphasizes on physical state of lipid (supercooled melts, different lipid modifications).