Controlled transdermal delivery of model drug compounds by MEMS microneedle array

This article reports an in vitro study of microneedle-array-enhanced transdermal transport of model drug compounds dispersed in chitosan films. Each microneedle array has 400 out-of-plane, needle-shaped microstructures fabricated using micro-electro-mechanical systems (MEMS) technology to ensure adequate mechanical strength and high precision, and consistency. A nanometer coating on the microneedles ensured the biocompatibility that is important in the application of transdermal drug delivery. Model drugs selected to investigate skin permeation in vitro were calcein, a small molecule (molecular weight, 623 d) that has little skin penetration, and bovine serum albumin (BSA) (molecular weight, 66,000 d), a hydrophilic biological macromolecule. A Franz permeation cell was used to characterize the permeation rate of calcein and BSA through the rat skin. The transdermal transport behavior of BSA was investigated from solid films coated on the surface of microneedle arrays with various chitosan concentrations, film thicknesses, and BSA contents. The BSA permeation rate decreased with the increase of the chitosan concentration; the thicker the film, the slower the permeation rate. In addition, the permeation rate increased with the increase of BSA loading dose. A linear relationship existed between the permeation rate and the square root of the BSA loading dose. Results showed that the chitosan hydrophilic polymer film acts as a matrix that can regulate the BSA release rate. The controlled delivery of BSA can be achieved using the BSA-containing chitosan matrix film incorporated with the microneedle arrays. This will provide a possible way for the transdermal delivery of macromolecular therapeutic agents such as proteins and vaccines.     

Skin permeation of propranolol from polymeric film containing terpene enhancers for transdermal use

To develop the suitable film formulations of propranolol hydrochloride (PPL) containing enhancers for transdermal use, polymeric film formulations were prepared by employing ethyl cellulose (EC) and polyvinyl pyrrolidone (PVP) as a film former, and dibutyl phthalate (DBP) as a plasticizer. Terpenes such as menthol and cineole, and propylene glycol (PG) were also employed as a chemical enhancer to improve the skin penetration of PPL. The film preparations were characterized in physical properties such as uniformity of drug content, thickness and moisture uptake capacity. Release and skin permeation kinetics of PPL from film preparations were examined in the in vitro studies using a Franz-type diffusion cell. The uniformity of drug content was evidenced by the low S.D. values for each film preparation. The moisture uptake capacity and drug release rate increased with the increase of PVP in each preparation. Enhancers examined in the present study also increased the moisture uptake capacity and release rate of PPL from the film preparations. Increasing the concentration of PPL from 1 to 2 mg/cm2 in the film enhanced the release rate of PPL, while no effect of enhancer concentrations on the release rate from the film preparations was observed. In vitro skin permeation study showed that cineole was the most promising enhancer among the enhancers examined in the present study and suggested that the suitable compositions of film preparation would be EC:PVP:PPL=6:3:4 with 10% (w/w) cineole and 7:2:4 with 10% (w/w) PG and cineole, which provided high skin permeation rates at 93.81+/-11.56 and 54.51+/-0.52 microg/cm2/h, respectively.     

Drug release kinetics from polymeric films containing propranolol hydrochloride for transdermal use

Polymeric films containing propranolol hydrochloride (PPN) were formulated and evaluated with a view to select a suitable formulation for the development of transdermal drug delivery systems. Films containing different ratios of ethyl cellulose (EC), poly(vinylpyrrolidone) (PVP), and PPN were prepared by mercury substrate method. In vitro drug release and skin permeation studies were conducted using paddle over disk and modified Franz diffusion cell, respectively. The drug release profiles from the polymeric film indicated that the drug content in the film decreased at an apparent first-order rate, whereas the quantity of drug release was proportional to the square root of time. The release rate of PPN increased linearly with increasing drug concentration and PVP fraction in the film, but was found to be independent of film thickness. The increase in release rate may be due to leaching of hydrophilic fraction of the film former, which resulted in the formation of pores. It was also observed that the release of drug from the films followed the diffusion-controlled model at low drug concentration. A burst effect was observed initially, however, at high drug loading level, which may be due to rapid dissolution of the surface drug followed by the diffusion of the drug through the polymer network in the film. The in vitro skin permeation profiles displayed increased flux values with increase of initial drug concentration in the film, and also with the PVP content. From this study, it is concluded that the films composed of EC/PVP/PPN, 9:1:3, 8:2:2, and 8:2:3, should be selected for the development of transdermal drug delivery systems using a suitable adhesive layer and backing membrane for potential therapeutic applications.     

Fabrication and evaluation of polymeric films for transdermal delivery of pinacidil

The objective of the present work was to fabricate Eudragit RL 100-polyvinyl acetate films and evaluate their potential for transdermal drug delivery in a quest to develop a suitable transdermal therapeutic system for pinacidil. The polymeric films (composed of Eudragit RL100 and polyvinyl acetate in 2:8, 4:6, 6:4, 8:2 ratios in films P-1, P-2, P-3, P-4 respectively, together with 5% w/w of pinacidil and 5% w/w of dibutylphthalate in all the films) were cast on a glass substrate and evaluated for physicochemical parameters viz. thickness, weight, folding endurance (a measure of fragility), percent elongation at break (a measure of flexibility), drug content uniformity, water absorption capacity, moisture vapour transmission, drug-polymer interaction, in vitro drug release and skin permeation profiles. The films were also evaluated for appearance, smoothness and transparency. The film finally selected was assessed for its skin irritation potential, and its stability on storage under accelerated temperature and humidity conditions. The values of thickness, weight, folding endurance, percent elongation at break, percentage water absorbed, moisture vapour transmission, cumulative amount of drug released and permeated for different films were in the following order: P-1 < P-2 < P-3 < P-4. The results suggest that Eudragit RL 100, a freely permeable polymer, has a major influence on the physicochemical profile of the films. The higher the quantity of Eudragit RL100 in the film, the better its strength and flexibility as well as its higher drug release and skin permeation potential. The final optimized film (with a composition of Eudragit RL 100: polyvinyl acetate: pinacidil monohydrate: dibutylphthalate in 8.0:2.0:0.5:0.5 ratio) was found to be the best in terms of drug release (cumulative amount of drug released in 48 h was 96.09%) and skin permeation (permeability coefficient, 0.0164 cm/h). There was no apparent drug-polymer interaction in the films. The optimized film was seemingly free of potentially hazardous skin irritation. The film was found to be stable and intact at ambient temperature and humidity conditions. The films hold promise for the development of a matrix type transdermal therapeutic system for pinacidil.     

Triple-component nanocomposite films prepared using a casting method: Its potential in drug delivery

The purpose of this study was to fabricate a triple-component nanocomposite system consisting of chitosan, polyethylene glycol (PEG), and drug for assessing the application of chitosan–PEG nanocomposites in drug delivery and also to assess the effect of different molecular weights of PEG on nanocomposite characteristics. The casting/solvent evaporation method was used to prepare chitosan–PEG nanocomposite films incorporating piroxicam-β-cyclodextrin. In order to characterize the morphology and structure of nanocomposites, X-ray diffraction technique, scanning electron microscopy, thermogravimetric analysis, and Fourier transmission infrared spectroscopy were used. Drug content uniformity test, swelling studies, water content, erosion studies, dissolution studies, and anti-inflammatory activity were also performed. The permeation studies across rat skin were also performed on nanocomposite films using Franz diffusion cell. The release behavior of films was found to be sensitive to pH and ionic strength of release medium. The maximum swelling ratio and water content was found in HCl buffer pH 1.2 as compared to acetate buffer of pH 4.5 and phosphate buffer pH 7.4. The release rate constants obtained from kinetic modeling and flux values of ex vivo permeation studies showed that release of piroxicam-β-cyclodextrin increased with an increase in concentration of PEG. The formulation F10 containing 75% concentration of PEG showed the highest swelling ratio (3.42 ± 0.02) in HCl buffer pH 1.2, water content (47.89 ± 1.53%) in HCl buffer pH 1.2, maximum cumulative drug permeation through rat skin (2405.15 ± 10.97 μg/cm²) in phosphate buffer pH 7.4, and in vitro drug release (35.51 ± 0.26%) in sequential pH change mediums, and showed a significantly (p < 0.0001) higher anti-inflammatory effect (0.4 cm). It can be concluded from the results that film composition had a particular impact on drug release properties. The different molecular weights of PEG have a strong influence on swelling, drug release, and permeation rate. The developed films can act as successful drug delivery approach for localized drug delivery through the skin.     

The formation and permeability of drugs across free pectin and chitosan films prepared by a spraying method.

This study has investigated the permeation of drugs through free films made of pectin and chitosan. The background for this study is the intended use of the films as coating material in a colon-specific drug delivery device. The factors that varied when making the films were the pectin source and grade of the pectin, degree of deacetylation of the chitosan and ratio between pectin and chitosan. The permeability of the model drug in 0.1 M HCl was low with an average drug release of 1.3 x 10(-3)%/cm. The films containing high content of chitosan showed exponential kinetics while the films containing high content of pectin showed 0-order kinetics. The release of drug in phosphate buffer pH 6.8 showed 0-order kinetics. The lowest permeability was obtained for a film consisting of a high content of pectin to chitosan, chitosan with a high degree of deacetylation and non-amidated low methoxylated citrus pectin. The permeation of paracetamol for this combination was 9.4 x 10(3)%/cm. This film combination had a combined diffusion of only 0.046%/cm after 1 h in 0.1 M HCl and 4 h in phosphate buffer pH 6.8.     

Matrix type transdermal drug delivery systems of metoprolol tartrate: in vitro characterization

The monolithic matrix type transdermal drug delivery system of metoprolol tartrate were prepared by the film casting on a mercury substrate and characterised in vitro by drug release studies, skin permeation studies and drug-excipients interaction analysis. Four formulations were developed, which differed in the ratio of matrix-forming polymers. Formulations MT-1, MT-2, MT-3 and MT-4 were composed of Eudragit RL-100 and polyvinyl pyrrolidone K-30 with the following ratios: 2:8, 4:6, 6:4 and 8:2, respectively. All the four formulations carried 10% (m/m) of metoprolol tartrate, 5% (m/m) of PEG-400 and 5% (m/m) of dimethyl sulfoxide in isopropyl alcohol: dichloromethane (40:60). Cumulative amounts of the drug released in 48 hours from the four formulations were 61.5, 75.4, 84.3 and 94.5%, respectively. The corresponding values for cumulative amounts of the permeated drug for the said formulations were 53.5, 62.5, 69.8 and 78.2%. On the basis of in vitro drug release and skin permeation performance, formulation MT-4 was found to be better than the other three formulations and it was selected as the optimized formulation.     

Optimization of chitosan film as a substitute for animal and human epidermal sheets for in vitro permeation of polar and non polar drugs

The present investigation is aimed at preparing chitosan films capable of simulating the flux of modal drugs, 5-fluorouracil (5-FU) and indomethacin (INDO), across rat, rabbit and human cadaver epidermal sheets. Application of statistical design revealed that the concentration of chitosan, crosslinking time and concentration of crosslinking agent significantly influenced the in vitro flux of 5-FU and INDO across chitosan films. Multiple linear regression revealed a linear influence of all these active variables on 5-FU and INDO flux. It was deduced from atomic absorption spectroscopic analyses, DSC and IR spectroscopic data that 5% (m/V) sodium tripolyphosphate (NaTPP) produced optimum crosslinking of chitosan films. The in vitro permeation of both 5-FU and INDO across optimized film formulations was found to be comparable to that obtained across rat, rabbit and human epidermal sheets. These results indicate that optimized chitosan films have a potential to be developed as a substitute for animal and human cadaver epidermal sheets for preliminary in vitro permeation studies.     

Self-adhesive thin films for topical delivery of 5-aminolevulinic acid.

Self-adhesive thin-films have been developed as a topical delivery system for 5-aminolevulinic acid (ALA). The thin films are suitable for use during the photodynamic therapy of epithelial skin tumors. They are composed of a combination of the lipophilic polymer Eudragit NE and the lipophilic plasticiser acetyl tributyl citrate (ATBC). Because of its hydrophilicity, ALA forms suspension systems within these thin films, as evidenced by light microscopy. ALA release measured using Franz cells is very rapid from a Eudragit NE thin film loaded with 10% w/w ALA (200 microg ALA after 2.5 h), and even higher when ATBC is included. A Eudragit NE/ATBC (1: 2) thin film loaded with 20% w/w ALA releases 2000 microg ALA after 3.5 h. Combined release/permeation of ALA through excised membranes of human stratum corneum plus epidermis yielded fluxes of 50-100 microg ALA within 5 h for the Eudragit NE/ATBC (1: 2) thin film. The ATBC acts as a permeation enhancer for ALA. Scanning electron microscopy of the thin film surface shows protruding ALA particles which rapidly dissolve on contact with an aqueous medium. This surface dissolution mechanism is the cause of the rapid ALA release and hence also the high skin permeation in vitro. The mechanical properties of the thin films were also briefly examined. Adhesive strength increases with higher ATBC loading and decreases with higher ALA loading. Internal cohesion decreases with greater ATBC loading and increases with higher ALA loading. As part of this project, an improved derivatisation assay for gradient HPLC of ALA with 9Fluorenylmethyloxycarbonylchloride is also presented.     

Preparation and characterization of free mixed-film of pectin/chitosan/Eudragit RS intended for sigmoidal drug delivery.

Polyelectrolyte complex (PEC) film between pectin as an anionic polyelectrolyte and chitosan as a cationic species was prepared by blending two polymer solutions at weight ratio of 2:1 and then solvent casting method. Besides pectin/chitosan PEC film, Eudragit RS, pectin/Eudragit RS and pectin/chitosan/Eudragit RS films were also prepared by aforementioned method. In mixed-film formulations, a fixed weight ratio of 1:5 of pectin or pectin/chitosan complex to Eudragit RS was used. Characterizations of pectin/chitosan interaction in solution were investigated by turbidity and viscosity measurement and in the solid state by Fourier transform infrared (FTIR) spectroscopy, wide angle X-ray diffraction (WAXRD) and thermogravimetric analysis (TGA). It was observed that the swelling profile of pectin/chitosan film was pH-dependent and its swelling ratio in phosphate buffer solution (PBS) pH 7.4 was about 2.5-fold higher than that of PBS pH 6.0. Formulation containing only pectin/chitosan could not protect free film from high swelling in the aqueous media, therefore, Eudragit RS as a water-insoluble polymer must be included in the mixed-film. The formation of PEC between pectin and chitosan resulted in a decrease in the crystallinity and thermal stability caused by the interactions between polyions. Drug permeation or diffusion studies were carried out using Plexiglas diffusion cell consisting of donor and acceptor compartments. Theophylline was selected as a model drug to measure permeability coefficient. Drug permeation through pectin/chitosan/Eudragit RS showed a sigmoidal pattern; whereas drug diffusion through pectin/Eudragit RS and Eudragit RS films followed a linear characteristic. The drug permeation through the ternary mixed-film showed a burst release upon exposure to PBS pH 6.0. This mixed-film formulation showed the potential for sigmoidal drug delivery with an initial, controllable slow release followed by a burst release immediately after the change in pH. The burst drug permeation might possibly be due to change in film's porosity.     

Chitosan films and hydrogels of chlorhexidine gluconate for oral mucosal delivery

Topical delivery of antimicrobial agents is the most widely accepted approach aimed at prolonging active drug concentrations in the oral cavity. As most antifungals do not posses inherent ability to bind to the oral mucosa, this is best achieved through improved formulations. Chitosan, a partially deacetylated chitin, which is a biologically safe biopolymer, prolongs the adhesion time of oral gels and drug release from them. Chitosan also inhibits the adhesion of Candida albicans to human buccal cells and has antifungal activity. The antifungal agent, chlorhexidine gluconate (Chx), also reduces C. albicans adhesion to oral mucosal cells. The aim of this study was to design a formulation containing chitosan for local delivery of Chx to the oral cavity. Gels (at 1 or 2% concentration) or film forms of chitosan were prepared containing 0.1 or 0.2% Chx and their in vitro release properties were studied. The antifungal activity of chitosan itself as well as the various formulations containing Chx was also examined. Release of Chx from gels was maintained for 3 h. A prolonged release was observed with film formulations. No lag-time was observed in release of Chx from either gels or films. The highest antifungal activity was obtained with 2% chitosan gel containing 0.1% Chx.     

In vitro and in vivo characterization of novel biomaterial for transdermal application

Polymers have become an indispensable part in the design of a conventional as well as novel drug delivery system. Gum Copal (GC), a novel biomaterial obtained from Agathis species, is evaluated in the present study for its potential application as a matrix former in transdermal drug delivery systems. GC was initially characterized for various physicochemical properties and then mechanical characterization of the Plasticized films of GC was investigated. Verapamil hydrochloride (VH), owing to its pharmacokinetic properties, was selected as the model drug for the present work. Matrix type transdermal films of VH with GC, alone and in combination with polyvinyl pyrrolidone (PVP K-30), were developed and evaluated for various physicochemical properties. In-vitro drug release study was carried out using paddle over disk method and in-vitro skin permeation study was performed using human cadaver skin. On the basis of physicochemical properties, in-vitro drug release study and permeation performance, formulation F5 containing GC: PVP K-30 (60:40) was selected as an optimized formulation for in vivo study. Animal studies were carried out using Dawley rats and the data obtained from the plasma drug analysis showed that peak drug concentration of about 244.94 ± 1.25 ng/mL was achieved in 6 h after the application of the patch and plasma drug concentration was maintained till 24 h. Skin irritancy test results proved the suitability of the biomaterial for transdermal application. The drug polymer interaction studies carried out using UV, FTIR and TLC analysis indicated that drug and polymer were compatible. Due to reasonably good mechanical properties, low water vapor transmission and sustained release capability, GC seems to be a promising film former for transdermal drug delivery.     

In vitro and In vivo characterization of the transdermal delivery of sertraline hydrochloride Films

Background and the purpose of the study

Sertraline hydrochloride is a selective serotonin reuptake inhibitor principally used in the treatment of major depressive disorder. To maintain the therapeutic plasma drug concentration of the drug for prolonged period, the transdermal drug delivery has been chosen as an alternative route of drug delivery. The pharmacokinetic properties of sertraline hydrochloride make it suitable for transdermal delivery. The purpose of the study was to investigate the effect of polymers and penetration enhancers on the transdermal delivery of the drug in order to improve its therapeutic efficacy.

Methods

In the preparation of films, Eudragit RL 100, Eudragit RS 100, hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose were used as polymers. The films were characterized for thickness, tensile strength, drug content, moisture uptake, moisture content, water vapor transmission rate and drug release. The films exhibiting higher rates of drug release were subjected to study the effect of oleic acid and propylene glycol as penetration enhancers on skin permeation of sertraline hydrochloride. In vivo and skin irritation studies were performed for the optimized film.

Results

Films containing Eudragit RL 100, Eudragit RL 100 and HPMC showed the highest drug release of 94.34% and 96.90% respectively in a period of 42 hrs. The release data fitted into kinetic equations, yielded zero-order and fickian mechanism of drug release. There was a two-fold increase in skin permeation of sertraline hydrochloride in the presence of penetration enhancers in the film. The physical evaluation indicated the formation of smooth, flexible and translucent films. No skin irritation occurred on rabbit skin and the infrared studies showed the compatibility of the drug with the formulation excipients. The in vivo study revealed a constant plasma concentration of drug for long periods and the films containing penetration enhancers had achieved adequate plasma levels of the drug.

Conclusions

The obtained results indicated the feasibility for transdermal delivery of sertraline hydrochloride using eudragit RL 100 and HPMC.     

Development and characterization of transdermal drug delivery systems for diltiazem hydrochloride

Transdermal drug delivery system of diltiazem hydrochloride was developed to obtain a prolonged controlled drug delivery. Both the matrix diffusion controlled (MDC) and membrane permeation controlled (MPC) systems were developed. The matrix diffusion controlled systems used various combinations of hydrophilic and lipophillic polymers, whereas membrane permeation controlled systems were developed using the natural polymer chitosan. The MDC systems were prepared using the cast film method and the MPC systems by an adhesive sealing technique. Both the systems were characterized for in vitro and in vivo performance. The MDC systems were characterized for physicochemical properties such as tensile strength, moisture content, and water vapor transmission. The in vitro release studies showed that the release from the matrix diffusion controlled transdermal drug delivery systems follows a nonfickian pattern and that from the membrane permeation controlled transdermal drug delivery systems follow zero-order kinetics. The release from the matrix systems increased on increasing the hydrophilic polymer concentration, but the release from the membrane systems decrease on cross-linking of the rate controlling membrane and also on addition of citric acid to the chitosan drug reservoir gel. The in vivo studies of the selected systems showed that both systems are capable of achieving the effective plasma concentration for a prolonged period of time. The MPC system achieved effective plasma concentration a little more slowly than the MDC system, but it exhibited a more steady state plasma level for 24 hr.     

Development and in-vitro evaluation of transdermal matrix films of metoprolol tartrate

The transdermal matrix films of metoprolol tartrate (MT) were prepared by casting on mercury substrate employing different ratios of polymers, ethyl cellulose (EC) and polyvinyl pyrrolidone (PVP), using dibutyl phthalate (DBT) as a plasticizer. Four formulations were prepared. Formulations MF-1, MF-2, MF-3 and MF-4 were composed of EC and PVP in the following ratios: 4.5:0.5, 4:1, 3:2 and 2:3 respectively. The formulations were subjected to various physical characterization studies namely, thickness, weight variation, drug content, moisture uptake, in vitro drug release and in vitro skin permeation. The in vitro permeation studies were carried out across excised porcine ear skin using Franz diffusion cell. Cumulative amounts of the drug released in 24 hours from the four formulations were 69.58%, 96.13%, 98.85% and 99.60%, respectively. Corresponding values for the cumulated amounts of drug permeated across the porcine skin for the above matrix films were 124.38, 153.22, 156.46 and 163.25 mug/cm(2) respectively. By fitting the data into zero order, first order and Higuchi model, it was concluded that drug release from matrix films followed Higuchi model (r(2)=0.9147-0.9823), and the mechanism of release was diffusion mediated. Based on the physical evaluation, in vitro drug release & permeation characteristics, it was concluded that for potential therapeutic use, monolithic drug matrix films MF-3, composed of EC: PVP (3:2), may be suitable for the development of a transdermal drug delivery system of MT.     

In vitro release and characterization of chitosan films as dexamethasone carrier

Chitosan, a biodegradable and biocompatible polysaccharide, is a potentially useful material in various fields. We produced mono and bilayer chitosan films containing dexamethasone as a drug carrier for controlled release. The chitosan drug-loaded films were produced by a casting/solvent evaporation technique using 2 wt% acetic acid solution and distilled water and they were dried at room temperature. These films were characterized by release and swelling studies, DSC and ATR-FTIR. The total profile for water absorption was similar for the types of films developed. ATR-FTIR analysis showed little change in the band position of the O--H and N--H stretching from dexamethasone and chitosan, respectively. DSC analysis from bilayer film indicates that the dexamethasone peak was shifted from 256 to 240 degrees C. These results suggested an interaction between hydroxyl and amino groups of chitosan and hydroxyl groups of dexamethasone. In the drug release studies it was observed 89.6% release from the monolayer film in 8h and 84% from the bilayer film in 4 weeks. These results suggested that the chitosan sheet prepared in this study is a promising delivery carrier for dexamethasone.     

Formulation and evaluation of nitrendipine buccal films

A mucoadhesive drug delivery system for systemic delivery of nitrendipine, a calcium channel blocker through buccal route was formulated. Mucoadhesive polymers like hydroxypropylmethylcellulose K-100, hydroxypropylcellulose, sodium carboxymethylcellulose, sodium alginate, polyvinyl alcohol, polyvinyl pyrrolidone K-30 and carbopol-934P were used for film fabrication. The films were evaluated for their weight, thickness, percentage moisture absorbed and lost, surface pH, folding endurance, drug content uniformity, In vitro residence time, In vitro release and ex vivo permeation. Based on the evaluation of these results, it was concluded that buccal films made of hydroxylpropylcellulose and sodium carboxymethylcellulose (5±2% w/v; F-4), which showed moderate drug release (50% w/w at the end of 2 h) and satisfactory film characteristics could be selected as the best among the formulations studied.     

Hybrid Nanostructured Films for Topical Administration of Simvastatin as Coadjuvant Treatment of Melanoma

This work aims at (1) assessing the potential of repurposing simvastatin (SV) to support the most common therapies against melanoma and (2) developing an innovative topical adhesive film, composed by chitosan-coated nanostructured lipid carriers (Ch-NLC) used as drug vehicle. A factorial design approach was employed as the basis for the formulation development. Optimized Ch-NLC displayed a particle size of 108 ± 1 nm, a polydispersity index of 0.226, a zeta potential of 17.0 ± 0.6 mV, as well as an entrapment efficiency of 99.86 ± 0.08%, and SV loading of 14.99 ± 0.01%. The performance of SV-Ch-NLC films was assessed in terms of release, permeation, and adhesion, as critical quality attributes. Cutaneous tolerability and in vitro cytotoxicity studies were performed to warrant film safety and drug effectiveness, respectively. The topical films provided a sustained release kinetic profile of SV and were classified as nonirritant systems. The encapsulation of SV increased cytotoxicity in melanoma cells. The key role of squalene as nanostructuring agent of the lipid nanoparticle matrix and as permeation enhancer was highlighted, suggesting its key action for potentiating skin permeation and uptake into melanoma cells. Topical SV-Ch-NLC films are thus able to provide an in situ extended drug delivery and useful as coadjuvant treatment of melanoma skin lesions.     

Nanodispersion-loaded mucoadhesive polymeric inserts for prolonged treatment of post-operative ocular inflammation

Mucoadhesive polymeric films incorporated with ketorolac tromethamine-loaded nanodispersion aiming the sustained delivery of the drug to the cornea have been developed and characterised for the treatment of post-operative ocular inflammation. Nanodispersions were prepared by ionic gelation method with various concentrations of chitosan and sodium tripolyphosphate. The developed nanodispersions were analysed for morphology, particle size, dispersion homogeneity, zeta potential, entrapment efficiency and drug release. The nanodispersion that showed the smallest particle size and the highest entrapment efficiency was incorporated in optimised HPMC E15 and Eudragit RL100/HPMC K4m films. The formulation with optimum physicomechanical properties was selected to study its ex vivo transcorneal permeation through freshly excised bovine cornea in comparison with the nanodispersion and the marketed eye drops (Acular®). The polymeric ocular film showed greater permeation than aqueous eye drops. Moreover, the ocular film revealed a prolonged anti-inflammatory effect compared to eye drops when applied to inflamed rabbit’s eyes.     

Transdermal nicotine mixed natural rubber-hydroxypropylmethylcellulose film forming systems for smoking cessation: in vitro evaluations

Abstract

Novel film forming polymeric dispersions for transdermal nicotine delivery were prepared from deproteinized natural rubber latex (DNRL) blended with hydroxypropylmethylcellulose (HPMC) and dibutyl phthalate (DBP) or glycerin (GLY) as plasticizer. The preliminary molecular compatibility of ingredients was observed by Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry characterizations. All film forming polymeric dispersions were elegant in appearance and smooth in texture without agglomeration. Their pH was 7–8. In addition, their viscosity and spreadability showed good characteristics depended on HPMC and plasticizers blended. The transparent in situ dry films with good strength and elasticity were also confirmed by peeling-off. The nicotine release from them revealed an initial fast release that was similar to the release from a concentrated nicotine solution, and followed by slow release pattern from the in situ films. GLY blended formulation produced a higher amount of nicotine permeation through the in vitro pig skin than DBP blends. Ethanol mixing also enhanced nicotine permeation, but it affected the integrity of in situ films. The nicotine release and skin permeation kinetics were by a diffusion mechanism that was confirmed by the Higuchi's model. These formulations were safe without producing any severe skin irritation. However, for the stability they needed to be stored at 4?°C in tightly sealed containers.