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.     

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.     

Design,development, physicochemical,and in vitro and in vivo evaluation of transdermal patches containing diclofenac diethylammonium salt

In this study, matrix-type transdermal patches containing diclofenac diethylamine were prepared using different ratios of polyvinylpyrrolidone (PVP) and ethylcellulose (EC) by solvent evaporation technique. The drug matrix film of PVP and EC was casted on a polyvinylalcohol backing membrane. All the prepared formulations were subjected to physical studies (moisture content, moisture uptake, and flatness), in vitro release studies and in vitro skin permeation studies. In vitro permeation studies were performed across cadaver skin using a modified diffusion cell. Variations in drug release profiles among the formulations studied were observed. Based on a physicochemical and in vitro skin permeation study, formulation PA4 (PVP/EC, 1:2) and PA5 (PVP/EC, 1:5) were chosen for further in vivo experiments. The antiinflammatory effect and a sustaining action of diclofenac diethylamine from the two transdermal patches selected were studied by inducing paw edema in rats with 1% w/v carrageenan solution. When the patches were applied half an hour before the subplantar injection of carrageenan in the hind paw of male Wistar rats, it was observed that formulation PA4 produced 100% inhibition of paw edema in rats 12 h after carrageenan insult, whereas in the case of formulation PA5, 4% mean paw edema was obtained half an hour after the carrageenan injection and the value became 19.23% 12 h after the carrageenan insult. The efficacy of transdermal patches was also compared with the marketed Voveran gel and it was found that PA4 transdermal patches produced a better result as compared with the Voveran gel. Hence, it can be reasonably concluded that diclofenac diethylamine can be formulated into the transdermal matrix type patches to sustain its release characteristics and the polymeric composition (PVP/EC, 1:2) was found to be the best choice for manufacturing transdermal patches of diclofenac diethylamine among the formulations studied.     

A comparison between povidone-ethylcellulose and povidone-eudragit transdermal dexamethasone matrix patches based on in vitro skin permeation.

The present study was designed to develop a suitable matrix type transdermal drug delivery system (TDDS) of dexamethasone using blends of two different polymeric combinations, povidone (PVP) and ethylcellulose (EC) and Eudragit with PVP. Physical studies including moisture content, moisture uptake, flatness to study the stability of the formulations and in vitro dissolution of the experimental formulations were performed to determine the amount of dexamethasone present in the patches were performed and scanning electron microscopy (SEM) photographs of the prepared TDDS were taken to see the drug distribution pattern. Drug-excipient interaction studies were carried out using Fourier transform infrared (FTIR) spectroscopic technique. In vitro skin permeation study was conducted in a modified Franz's diffusion cell. All the formulations were found to be suitable for formulating in terms of physicochemical characteristics and there was no significant interaction noticed between the drug and polymers used. In vitro dissolution studies showed that the drug distribution in the matrix was homogeneous and the SEM photographs further demonstrated this. The formulations of PVP:EC provided slower and more sustained release of drug than the PVP:Eudragit formulations during skin permeation studies and the formulation PVP:EC (1:5) was found to provide the slowest release of drug. Based on the above observations, it can be reasonably concluded that PVP-EC polymers are better suited than PVP-Eudragit polymers for the development of TDDS of dexamethasone.     

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.     

Transdermal atenolol releasing system: an approach towards its development

A polymer matrix system for transdermal delivery of atenolol was developed for its prolonged and controlled release using different ratios of ethylcellulose and hydroxypropyl methylcellulose. These polymeric matrix films were characterized for thickness, tensile strength, moisture content and drug content. They were also studied for in vitro drug release and in vitro drug skin permeation. The drug release from the films was found to be Fickian diffusion type and exhibiting linear relationship between drug release (Q) vs. square root of time (t0.5). The in vitro skin permeation of drug from transdermal drug delivery system (TDDS) was evaluated using dermatomed pig skin. The product which shows in vitro drug skin permeation near to 64 mcg/h/ml was selected for in vivo studies. The in vivo studies revealed that Ma EC HPMC 46 is most effective among the other polymeric matrix TDDS. The AUC0-28 with Ma EC HPMC 46 was better than orally administered conventional doses at twelve hours interval (AUC0-28 1587 ng h/ml) as well as no trough and peaks in drug plasma level was recorded with TDDS. Hence, it could be concluded that the designed polymeric matrix TDDS of atenolol could be used successfully for effective and prolonged delivery of atenolol. However, it further demands exploration in clinic, an insight vision towards the development of TDDS for commercial use.     

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.     

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.     

Controlled systemic delivery of indomethacin using membrane-moderated, cream formulation-based transdermal devices

The present study was carried out to design a viable and practically effective transdermal systems of indomethacin using cream-based drug reservoirs and suitable rate controlling membranes. As vehicles, a more lipophilic base (F(1)) and a cream formulation containing predominant aqueous phase (F(2)) were chosen to study the influence of vehicle nature and role of permeation enhancers that increases thermodynamic activity and to provide diffusible species of drug to skin. Rate controlling membranes of cellulose acetate (CA) and ethyl cellulose (EC) with polyvinyl pyrollidine and hydroxypropyl methyl cellulose were used to design transdermal devices. In vivo, effective plasma concentrations of indomethacin are maintained up to 24 hr whereas oral formulation showed only up to 8 hr. Although the plasma drug levels between both EC films differ insignificantly, PVP film showed a better pharmacokinetic profile. The pharmacodynamic performance of the transdermal devices exhibited good anti-inflammatory activity over 24 hr compared with orally administered indomethacin. In vivo studies indicate the superiority of CA films over the EC films. Further, enhancement may be achieved with other classic enhancers/enhancement strategies with such devices containing aqueous cream vehicle and the optimum membranes.     

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.     

Bioequivalence of marketed transdermal delivery systems for tulobuterol

Tulobuterol permeation through skin from various transdermal delivery systems has been compared for the bioequivalence among devices marketed. Both the permeation profiles across the hairless mouse skin and the release profiles from the devices were measured under well-controlled in vitro conditions. The release rate of the drug from the devices was appreciably higher than the penetration rate across the intact skin, indicating the skin-controlled delivery systems. However the deviation between the release rate and the permeation rate differs depending upon the system design. The brand patch showed the least difference between the release and permeation profiles among the brand and three generic devices examined. From the in vitro permeation profiles for both intact and stripped skins, the diffusion coefficient and the partition coefficient were evaluated on the basis of bi-layer skin model. The effect of the stratum corneum thickness was then simulated by SKIN-CAD. The simulated profile has suggested that the clinical performance for transdermal tulobuterol delivery is influenced not only by the thickness of the stratum corneum but by the device design as well. This is particularly the case for the stratum corneum, thinner than about 10 microm or damaged skin with the decreased barrier capacity. For the stratum corneum thicker than 20 microm, on the other hand, the clinical performance may not be significantly influenced by the device designs investigated in this study.     

不同基质和透皮促进剂对秋水仙碱凝胶剂体外透皮特性的影响

目的优选秋水仙碱凝胶剂基质和相应的透皮促进剂,为制备秋水仙碱透皮给药新制剂提供参考资料。方法采用改良的Franz扩散池法,并通过RP-HPLC法测定接收液中秋水仙碱的含量。结果3种基质的秋水仙碱凝胶体外透皮比率为Carbopol基质凝胶>HPMC基质凝胶>CMC-Na基质凝胶。以Carbopol为基质,加入几种透皮促进剂后,秋水仙碱凝胶的体外透皮速率为丙二醇>冰片>氮酮>薄荷油。结论凝胶剂作为秋水仙碱透皮吸收新剂型可行。     

Enhanced transdermal controlled delivery of glimepiride from the ethylene-vinyl acetate matrix

An ethylene-vinyl acetate (EVA) matrix containing glimepiride was prepared as a potential transdermal drug delivery system. Permeation studies of quinupramine through the EVA copolymer membrane were carried out using a two-chamber diffusion cell. The rate of drug permeation through the EVA membrane was proportional to the PEG 400 volume fraction. The release of glimepiride from the EVA matrix was examined using a modified Franz diffusion cell. A plasticizer was added to prepare the pore structure of the EVA matrix in order to increase the rate of drug release. The effects of PEG 400, drug concentration, temperature, and plasticizer on the drug release rate were investigated. Various types of enhancers were added to an EVA matrix containing 2% glimepiride in an attempt to increase the level of skin permeation of quinupramine through an EVA matrix. The effects of the enhancers on the level of glimepiride permeation through the skin were evaluated using Franz diffusion cells fitted with intact excised rat skin. The rate of drug release from the EVA matrix increased with increasing PEG 400 volume fraction, temperature, and drug loading. The estimated activation energy of drug release was 7.274 kcal/mol for 2% drug loading dose. The release of glimepiride from the EVA matrix followed a diffusion-controlled model, where the quantity released per unit area was proportional to the square root of time. The controlled release of glimepiride was achieved using the EVA polymer including the plasticizer. Among the plasticizers used, such as the alkyl citrates and phthalates groups, diethyl phthalate slightly increased the rate of glimepiride release. Among the various enhancers used, such as the non-ionic surfactants, the glycerides, the propylene glycol derivatives, fatty acids (saturated or unsaturated), and pyrrolidones, linoleic acid showed the highest permeation rate; 3.17-times higher than the control. In conclusion, an EVA matrix containing a permeation enhancer can be used for the transdermal controlled delivery of glimepiride.     

Transdermal atenolol releasing system: An approach towards its development

A polymer matrix system for transdermal delivery of atenolol was developed for its prolonged and controlled release using different ratios of ethylcellulose and hydroxypropyl methylcellulose. These polymeric matrix films were characterized for thickness, tensile strength, moisture content and drug content. They were also studied for in vitro drug release and in vitro drug skin permeation. The drug release from the films was found to be Fickian diffusion type and exhibiting linear relationship between drug release (Q) vs. square root of time (t^0.5). The in vitro skin permeation of drug from transdermal drug delivery system (TDDS) was evaluated using dermatomed pig skin. The product which shows in vitro drug skin permeation near to 64 mcg/h/ml was selected for in vivo studies. The in vivo studies revealed that Ma EC HPMC 46 is most effective among the other polymeric matrix TDDS. The AUC_0–28 with Ma EC HPMC 46 was better than orally administered conventional doses at twelve hours interval (AUC_0–28 1587 ng h/ml) as well as no trough and peaks in drug plasma level was recorded with TDDS. Hence, it could be concluded that the designed polymeric matrix TDDS of atenolol could be used successfully for effective and prolonged delivery of atenolol. However, it further demands exploration in clinic, an insight vision towards the development of TDDS for commercial use.     

Controlled Systemic Delivery of Indomethacin Using Membrane-Moderated,Cream Formulation–Based Transdermal Devices

The present study was carried out to design a viable and practically effective transdermal systems of indomethacin using cream-based drug reservoirs and suitable rate controlling membranes. As vehicles, a more lipophilic base (F₁) and a cream formulation containing predominant aqueous phase (F₂) were chosen to study the influence of vehicle nature and role of permeation enhancers that increases thermodynamic activity and to provide diffusible species of drug to skin. Rate controlling membranes of cellulose acetate (CA) and ethyl cellulose (EC) with polyvinyl pyrollidine and hydroxypropyl methyl cellulose were used to design transdermal devices. In vivo, effective plasma concentrations of indomethacin are maintained up to 24 hr whereas oral formulation showed only up to 8 hr. Although the plasma drug levels between both EC films differ insignificantly, PVP film showed a better pharmacokinetic profile. The pharmacodynamic performance of the transdermal devices exhibited good anti-inflammatory activity over 24 hr compared with orally administered indomethacin. In vivo studies indicate the superiority of CA films over the EC films. Further, enhancement may be achieved with other classic enhancers/enhancement strategies with such devices containing aqueous cream vehicle and the optimum membranes.     

Ex vivo Permeation Kinetics of Zidovudine from Pseudolatex Acrylic Film Across Pig Ear Epidermis

The permeation of ionic compounds through lipophilic skin membrane can be enhanced by converting the impermeable ionized drug into a more permeable unionized form with pH-adjusting excipients. The osmotic influx of water into the device core, upon application on the human skin, dissolve the drug and pH-adjusting adjuvant allowing the partitioning and subsequent permeation of unionized drug from the transdermal device core. The present investigation was aimed to evaluate the feasibility of water activated pH-controlled pseudolatex films for transdermal delivery of zidovudine by ex vivo tests. The monolithic pseudolatex transdermal film of zidovudine was prepared by solvent change followed by solvent casting technique using Eudragit RL 100 and Eudragit RS 100 in varying proportions with pH 7.4 in the device core. The prepared films were of desired physicochemical properties. The SEM photomicrographs of drug loaded formulations exhibited uniformity with rough surface and no traces of crack or pores. The ex vivo skin permeation study across pig ear epidermis in Keshary-Chien glass diffusion cell showed that the drug permeability was controlled by the osmotic influx of water into the device core and consequent partition of dissolve drug into and diffusion through the skin. The formulation F2a with 10 % w/w of zidovudine dispersed in the polymer matrix composed of Eudragit RL 100 and Eudragit RS 100 at the ratio of 1:2, respectively, showed nearly the desired flux at 239.09 μg/cm2/h. A patch area of 117.48 cm2 would be required for transdermal delivery of zidovudine to obtain therapeutic plasma concentration at 0.3 μg/ml.     

Development and characterization of skin permeation retardants and enhancers: a comparative study of levothyroxine-loaded PNIPAM, PLA, PLGA and EC microparticles

Polymeric microparticles suitable for topical and transdermal delivery systems were studied using poly D,L lactide (PLA), poly D,L lactide co glycoside (PLGA), poly (N-isopropylacrylamide) (PNIPAM) and ethyl cellulose (EC). Drug encapsulation efficacy, microparticle stability and skin permeation studies of levothyroxine loaded microparticles were carried out using excised human skin, and the skin permeation pattern was observed using confocal laser scanning microscopy. It was found that ethyl cellulose microparticles had the highest drug encapsulation and minimal drug leakage during the 14 week storage period. The PNIPAM microparticles had the lowest drug encapsulation efficiency and a fast degradation rate. The PLGA microparticles exhibited a temperature dependent drug leakage. Permeation studies using a flow-through diffusion cell indicated that the polymer transition temperature (T(g)) may influence the skin permeation rate of levothyroxine. Polyesters (PLA and PLGA) and PNIPAM acted as a skin penetration retardant and caused skin accumulation of the drug. These microparticles have potential use in skin formulations containing sunscreens and other active ingredients that are meant to be concentrated on the skin surface. However, skin permeation was observed from EC microparticles, therefore such polymers may be used as carriers in transdermal formulations to help achieve therapeutic concentrations of the drug in the plasma.     

Enhanced Controlled Transdermal Delivery of Ambroxol from the EVA Matrix

To avoid the systemic adverse effects that might occur after oral administration, transdermal delivery of ambroxol was studied as a method for maintaining proper blood levels for an extended period. Release of ambroxol according to concentration and temperature was determined, and permeation of drug through rat skin was studied using two chamber-diffusion cells. The solubility according to PEG 400 volume fraction was highest at 40% PEG 400. The rate of drug release from the EVA matrix increased with increased temperature and drug loading doses. A linear relationship existed between the release rate and the square root of loading rate. The activation energy (Ea) was measured from the slope of the plot of log P versus 1000/T and was found to be 10.71, 10.39, 10.33 and 9.87 kcal/mol for 2, 3, 4 and 5% loading dose from the EVA matrix, respectively. To increase the permeation rate of ambroxol across rat skin from the EVA matrix, various penetration enhancers such as fatty acids (saturated, unsaturated), propylene glycols, glycerides, pyrrolidones, and non-ionic surfactants were used. The enhancing effects of the incorporated enhancers on the skin permeation of ambroxol were evaluated using Franz diffusion cells fitted with intact excised rat skin at 37° using 40% PEG 400 solution as a receptor medium. Among the enhancers used, polyoxyethylene-2-oleyl ether increased the permeation rate by 4.25-fold. In conclusion, EVA matrix containing plasticizer and permeation enhancer could be developed for enhanced transdermal delivery of ambroxol.     

Deproteinized natural rubber film forming polymeric solutions for nicotine transdermal delivery

Film forming polymeric solutions were prepared from DNRL blended with MC, PVA, or SAG, together with dibutylphthalate or glycerine used as plasticizers. These formulations were easily prepared by simple mixing. In a preliminary step, in situ films were prepared by solvent evaporation in a Petri-dish. Their mechanical and physicochemical properties were determined. The in vitro release and skin permeation of nicotine dissolved in these blended polymers were investigated by a modified Franz diffusion cell. The formulations had a white milky appearance, and were homogeneous and smooth in texture. Their pH was suitable for usage in skin contact. The mechanical property of in situ films depended on the ingredients but all compatible films were in an amorphous phase. The DNRL/PVA was shown to be the most suitable mixture to form completed films. The in vitro release and skin permeation studies demonstrated a biphasic release that provided an initial rapid release followed by a constant release rate that fitted the Higuchi’s model. Nicotine loaded DNRL/PVA series were selected for the stability test for 3 months. These formulations needed to be kept at 4°C in tight fitting containers. In conclusion, film forming polymeric solutions could be developed for transdermal nicotine delivery systems.     

Design and evaluation of a bioadhesive film for transdermal delivery of propranolol hydrochloride

The objective of the study was to develop a suitable trans-dermal delivery system for propranolol hydrochloride (PPL) via employing chitosan as a film former. Drug concentration uniformity, thickness, moisture uptake capacity and skin bioadhesion of the films were characterized. The effects of chitosan and PPL concentration and different penetration enhancers on the release and permeation profiles from the films were investigated. Skin irritation of the candidate film was evaluated. Chitosan film (PPL 2 mg cm(-2), chitosan 2%, m/m, cineol 10%, m/m) was found nonirritant and achieved 88.2% release after 8 hours in phosphate buffer. Significant high (p < 0.001) permeation of PPL through rat skin was obtained using this film compared to the film without enhancer (about 8 times enhancement factor), making it a promising trans-dermal delivery system for PPL.