Development of matrix patches for transdermal delivery of a highly lipophilic antiestrogen

The aim of this study was to develop matrix-type transdermal systems (TDSs) containing the highly lipophilic (log P = 5.82) antiestrogen (AE) and the permeation enhancers propylene glycol and lauric acid. For that purpose, permeation of AE from various adhesive matrices through excised skin of hairless mice was evaluated. It was found that pretreatment of the skin with permeation enhancers raised the transdermal flux of subsequently applied antiestrogen. Highest steady-state transdermal fluxes (1.1 µg cm^-2 h^-1) were obtained from Gelva®, polyacrylate adhesive, followed by 0.55 µg cm^-2 h^-1 from Oppanol® polyisobutylene, 0.31 µg cm^-2 h^-1 from BIO-PSA® silicone, and 0.12 µg cm^-2 h^-1 from Sekisui polyacrylate matrices. In order to develop TDS with high content of fluid permeation enhancer propylene glycol, two different strategies were investigated. One strategy was the addition of hydroxypropyl cellulose (HPC) as thickening agent to Gelva matrices. This allowed for propylene glycol loading levels of up to 30%, resulting in transdermal AE fluxes of 0.09 µg cm^-2 h^-1. On the other hand, a fleece-laminated backing foil was loaded with the described permeation enhancer formulation and laminated with polyacrylate adhesive layer, resulting in transdermal AE fluxes of 0.06 µg cm^-2 h^-1. However, application of these TDSs on skin pretreated with permeation enhancers raised the fluxes to 2.6 µg cm^-2 h^-1 from Gelva/HPC and 0.46 µg cm^-2 h^-1 from fleece/Sekisui.     

Limonene and Related Compounds as Potential Skin Penetration Promoters

A transdermal therapeutic system can be developed by promoting the skin permeability of drugs with some materials. In this study, the promoting effect of terpenes present in essential oils on the percutaneous absorption of indomethacin from alcoholic hydrogels was investigated in rats in vivo. The enhancing activity of terpenes was expressed quantitatively as a quadratic function of lipophilicities of the terpenes, measured as a lipophilic index. Further increase in the significant level was observed when the molecular weight of terpenes was included in this function as the second factor. The synergism of ethanol with d-limonene, selected from among the other terpenes, on the promoting activity was statistically investigated. It was evident that both d-limonene and ethanol were important factors for promoting the percutaneous absorption of indomethacin. A significant synergism of d-limonene with ethanol was also observed. As a possible mechanism for enhancement action of d-limonene and ethanol, it was considered that, at first, d-limonene penetrates into the skin under coexistence with ethanol and may change the barrier structure of the stratum corneum. The transfer of ethanol to the skin is thereby enhanced under the coexistence with d-limonene in the skin. Thus, the permeation of indomethacin can be promoted due to its affinity with ethanol.     

The effects of pressure-sensitive adhesives and solubilizers on the skin permeation of testosterone from a matrix-type transdermal delivery system

Matrix-type transdermal delivery systems of testosterone (TS) were formulated with three different pressure-sensitive adhesives (PSA). The effects of PSA, skin permeation enhancers, and solubilizers on the rat skin permeation rate of TS were systematically investigated. Without a solubilizer, the skin permeation rate of TS reached its maximum value when only 2% of TS was loaded in the matrix and the crystal formation in the matrix was very rapid and severe. Two surfactants differing in their hydrophile-lipophile balance (HLB) number were, therefore, considered. Span 80, which was of the lower HLB number, was more effective than Tween 80 in increasing the solubility, and thereby increasing the permeation rate of TS. Moreover, the concentrations of both the solubilizer and the skin permeation enhancer affected the skin permeation rate. Thus, the highest skin permeation rate (4.14 µg/cm²/hr) was achieved when 2% TS was loaded in DuroTak® 87-2516 together with 10% Span 80 and 3% dodecylamine, the permeation enhancer. In vivo study showed that the application of an experimental patch on rat abdominal skin resulted in a prompt and significantly higher plasma concentration of TS than that of a commercial product (Testoderm®) designed to apply on the scrotal skin. The area under the curve (AUC) increased linearly as the loading dose of TS increased up to 6%. Thus, based on these results, a non-scrotal matrix-type transdermal delivery system of TS could be developed.     

Development of a novel soft hydrogel for the transdermal delivery of testosterone

A soft hydrogel formulation for the transdermal delivery of testosterone (TS) was developed, and the effect of various skin-permeation enhancers was studied in vitro and in vivo. Testosterone was incorporated into a polyvinyl alcohol (PVA)-based soft hydrogel with polyisobutylene (PIB) and various skin-permeation enhancers (dodecylamine, HPE101, oleic acid, or lauric acid). In vitro rat-skin permeation of TS from the soft hydrogel was investigated using Keshary-Chien diffusion cells for 24 hr at 37°C. In vivo plasma-concentration profiles of TS after applying the soft hydrogel on the dorsal skin of rat were determined using a commercial radioimmunoassay kit. The formulated soft hydrogel formed a thin film on the skin within 2 to 3 min after application and remained in a dried-film state for at least 24 hr. Addition of PIB into the hydrogel to increase the adhesion resulted in a negligible reduction in the skin-permeation rate of TS. However, rat-skin permeation of TS increased with the addition of permeation enhancers both in vitro and in vivo. Dodecylamine at the concentration of 3% was the most effective among tested. Plasma concentration of TS significantly increased for at least 24 hr with the addition of dodecylamine. These results suggest the feasibility of the development of a soft hydrogel formulation for the transdermal delivery of TS.     

Design and evaluation of matrix diffusion controlled transdermal patches of verapamil hydrochloride

Transdermal patches of verapamil hydrochloride were prepared using four different polymers (individual and combination): Eudragit RL100 (ERL100), Eudragit RS100 (ERS100), hydroxypropyl methylcellulose 15 cps (HPMC), and ethyl cellulose (EC), of varying degrees of hydrophilicity and hydrophobicity. The effect of the polymers on the technological properties, i.e., drug release, water vapor transmission rate (WVTR), and percentage moisture loss (ML), percentage moisture absorption (MA), folding endurance, and thickness, was investigated. Different formulations were prepared in accordance with the 2³ factorial design, with ERL100 being the parent polymer. The patch containing ERL100 alone showed maximum WVTR, % MA, and % ML, which could be attributed to its hydrophilic nature. As expected, substitution with ERS100, HPMC, and EC decreased all the above values in accordance with their decreasing degree of hydrophilicity. In vitro release studies showed zero-order release of the drug from all the patches, and the mechanism of release was diffusion mediated. Moreover, the release of the drug was sustained and it extended over a period of 24 hr in all formulations. A12 emerged as the most satisfactory formulation insofar as its technological properties were concerned. Further, release and permeation of the drug from the most satisfactory formulation (A12) was evaluated through different biological barriers (shed snake skin, rabbit skin, and rat skin) to get an idea of the drug permeation through human skin. Shed snake's skin was found to be most permeable (82.56% drug release at 24 hr) and rat skin was least permeable (52.38%). Percutaneous absorption studies were carried out in rabbits. The pharmacokinetic parameters calculated from blood levels of the drug revealed a profile typical of a sustained release formulation, with the ability to maintain adequate plasma levels for 24 hr. [AUC: 3.09 mg/mL hr, C_max: 203.95 µg/mL, T_max: 8 hr]. It can therefore be concluded that the patch containing ERL100 and HPMC in the ratio 8:2 has achieved the objectives of transdermal drug delivery system, such as avoidance of first pass effect, extended release, and reduced frequency of administration.     

Evaluation of the physicochemical stability and skin permeation of glucosamine sulfate

Glucosamine sulfate (GS) is known to stop the degenerative process of osteoarthritis. Because most of the GS formulation on the market is in the oral form, an alternative formulation such as a transdermal delivery system (TDS) is necessary in order to increase patient compliance. As the initial step to develop a TDS of GS, the physicochemical stability and permeation study in rat skin were examined. Evaluation of the stability of GS at different pHs showed the compound to be most stable at pH 5.0. The degradation rate constant at 25°C was estimated to be 5.93 ×10^- 6 hr^- 1 (t₉₀~ 2.03 years) in a pH 5 buffer solution. Due to its hydrophilic characteristic, low skin permeability was expected of GS. However, the skin permeation rate was determined to be 13.27 µg/cm²/hr at 5% concentration. Results of this study suggest the possibility of developing GS into a transdermal delivery system.     

Enhanced percutaneous permeability of nicardipine hydrochloride by carvone across the rat abdominal skin

The purpose of this study was to investigate the effect of carvone on the permeation of nicardipine hydrochloride across the excised rat abdominal epidermis from 2% w/w hydroxypropyl cellulose (HPC) gel system. The HPC gel formulations containing nicardipine hydrochloride (1% w/w) and selected concentrations of carvone (0 to 12% w/w) were prepared, and evaluated for drug content, stability of the drug, and in vitro permeation of the drug through excised rat abdominal epidermis. The HPC gel was found to contain 99.98 to 101.6% of nicardipine hydrochloride, and the drug was found to be stable in the HPC gels. The permeation flux of nicardipine hydrochloride across rat epidermis was increased markedly by the addition of carvone to the HPC gels. A maximum flux of nicardipine hydrochloride (243.95.70 ± 1.90 µg/cm²/hr) was observed with an enhancement ratio of 7.9 when carvone was incorporated at a concentration of 12% w/w in the HPC reservoir system. The differential scanning calorimetry and Fourier transform-infrared data indicated that carvone increased the permeability of nicardipine hydrochloride across the rat epidermis by partial extraction of lipids in the stratum corneum. The results suggest that carvone may be useful for enhancing the skin permeability of nicardipine hydrochloride from transdermal therapeutic system containing HPC gel as a reservoir.     

In vitro skin permeation and retention of paromomycin from liposomes for topical treatment of the cutaneous leishmaniasis

Paromomycin (PA), a very hydrophilic antibiotic, has been tested as an alternative topical treatment against cutaneous leishmaniasis (CL). Although this treatment has shown promising results, it has not been successful in accelerating the recovery in most cases. This could be attributed to the low skin penetration of PA. Liposomal formulations usually provide sustained and enhanced drug levels in skin. The aim of this study was to prepare liposomal formulations containing PA and to investigate their potential as topical delivery systems of this antileishmanial. Large multilamellar vesicles (MLVs) were prepared by conventional solvent evaporation method. Large unilamellar vesicles (LUVs) were prepared by reverse-phase evaporation method. The lipids used were soybean phosphatidylcholine (PC) and PC:cholesterol (CH) (molar ratio 1:1). The skin permeation experiments across stripped and normal hairless mice skin were performed in modified Franz diffusion cells. The PA entrapment in LUV liposomes (20.4 ± 2.2%) was higher than that observed for MLV liposomes (7.5 ± 0.9%). Drug entrapment was 41.9 ± 6.2% and 27.2 ± 2.4% for PC and PC:CH LUV, respectively. The skin permeation was 1.55 ± 0.31%, 1.29 ± 0.40%, 0.20 ± 0.08%, and 0.50 ± 0.19% for PC LUV, PC:CH LUV, empty LUV + PA and aqueous solution, respectively. Controlled topical delivery, across stripped skin, was observed for PA entrapped in LUV liposomes.     

Transdermal delivery of ondansetron hydrochloride: effects of vehicles and penetration enhancers

The effects of vehicles and penetration enhancers on the in vitro permeation of ondansetron hydrochloride (OS) across dorsal hairless mouse skins were investigated. Various types of vehicles, including ester, alcohol, and ether and their mixtures were used, and then a series of fatty acids and fatty alcohols were employed as enhancers. Among pure vehicles used, water and ethanol showed high permeation fluxes, which were 48.2 ± 23.7 and 41.9 ± 17.9 µg/cm² per h, respectively. Even though propylene glycol monocaprylate (PGMC) alone did not show a high permeation rate, the skin permeability of OS was increased by the addition of diethylene glycol monoethyl ether (DGME); the highest flux was achieved at 40% of DGME. Also, the combination of PGMC and ethanol (80:20) or PGMC and propylene glycol (PG) (60:40) increased the permeation flux by six- and two-fold, respectively, compared to PGMC alone. The synergistic enhancement was also obtained by using PG-oleyl alcohol (OAl) cosolvent. The greatest flux was attained by the addition of unsaturated fatty acids at 3% concentration to PG. The enhancement factors with the addition of oleic acid or linoleic acid to PG were about 1250 and 450, respectively. But saturated fatty acids failed to show a significant enhancing effect. When the PGMC-DGME (60:40) cosolvent system was used as a vehicle, all fatty acids, including unsaturated fatty acids, failed to show significant enhancing effects. The results indicate that the combinations of oleic acid, linoleic acid, or oleyl alcohol with PG, or PGMC-DGME (60:40) cosolvent could be used for the design of the OS transdermal system.     

Transdermal drug delivery system of haloperidol to overcome self-induced extrapyramidal syndrome

Haloperidol (HAL), an antipsychotic, is associated with side effects of drug-induced extrapyramidal syndrome (EPS) in conventional monotherapy. Controlled released transdermal dosage form (TDDS) of the drug was designed for maintenance therapy. Matrix-diffusion type transdermal film of HAL was designed with Eudragit NE 30D copolymer without permeation enhancer in different combinations. For the feasibility studies, all standard evaluations were performed, and their results pointed toward the suitability of TDDS. The drug release and permeation studies in Franz diffusion cell in 20% PEG-normal saline followed the Higuchi equation with optimum correlation coefficient. The neuroleptic efficacy was confirmed by maximum graded response in a rotarod apparatus. The neuroleptic-induced catatonia (EPS) in albino rats was minimum with a score of zero over a 72-hr study. The pharmacokinetic parameters in rabbit model showed a very significant prolongation of action up to 72 hr with steady-state plasma concentration (cp_ss) of 11.58 ng/mL. Thus, the HAL-loaded TDDS improved the therapeutic profile by preventing the neuroleptic-induced EPS and might be a better alternative during its long period of psychiatric treatment over conventional dosage form.     

Influence of hydroxypropyl-beta-cyclodextrin on the transdermal permeation and skin accumulation of oxybenzone

The objective of the present study was to determine the effects of hydroxypropyl-β-cyclodextrin (HPCD) concentration on the transdermal permeation and skin accumulation of a model ultraviolet (UV) absorber, oxybenzone. The concentration of oxybenzone was held constant at 2.67 mg/mL for all formulations, while the HPCD concentrations varied from 0 to 20% (w/w). Complexation of oxybenzone by HPCD was demonstrated by differential scanning calorimetry. A modified Franz cell apparatus was used in the transdermal experiments, with aliquots of the receptor fluid assayed for oxybenzone by high-performance liquid chromatography. From the permeation data, flux of the drug was calculated. Skins were removed from the diffusion cells at specified time points over a 24-hr period and the oxybenzone content in the skin determined. The aqueous solubility of oxybenzone increased linearly with increasing HPCD concentration, following a Higuchi A_L-type complexation. The stability constant of the reaction was calculated from the phase-solubility diagram and found to be 2047 M^-1. As the concentration of HPCD was increased from 0 to 10%, transdermal permeation and skin accumulation of oxybenzone increased. Maximum flux occurred at 10% HPCD, where sufficient cyclodextrin was added to completely solubilize all oxybenzone. When the concentration of HPCD was increased to 20%, both transdermal permeation and skin accumulation decreased. These data suggest the formation of a drug reservoir on the surface of the skin.     

Pharmacokinetic profile of a new matrix-type transdermal delivery system: diclofenac diethyl ammonium patch

A transdermal delivery system containing the anti-inflammatory analgesic diclofenac diethyl ammonium in an ethyl hexyl acrylate and vinyl acetate pressure-sensitive adhesive system was developed for percutaneous absorption. These patches were subjected to in vitro permeation and permeation enhancement studies through rat skin using a specially designed diffusion cell. Further, the work deals with percutaneous absorption studies carried out on both animals and human volunteers. The pharmacokinetic parameters calculated from the blood levels of the drug reveal a profile typical of a sustained-release formulation, with the ability to maintain adequate plasma levels for 24 hr (i.e., up to the next application). (Area under the curve [AUC]: 4.356 ± 1.3 mcg/ml.hr in animals and 0.442 ± 0.053 mcg/ml.hr in humans; T_max was 8 hr in both the cases, whereas C_max was 0.288 ± 0.088 mcg/ml in animals and 0.034 ± .008 mcg/ml in human volunteers.) The amount of the drug bioavailable for targeting the sites of action is lower than via the oral route, but the absorbed dose appears to be adequate for therapeutic use, particularly because of the absence of side effects.     

Two steps modification for improvement of cyclobenzaprine transdermal delivery: releasing from patch and penetrating through skin

The aim of this study was to improve the transdermal delivery of cyclobenzaprine (CBZ) from drug-in-adhesive patch which showed less side effects and better compliance. CBZ base was prepared and then characterized using differential scanning calorimetry (DSC). The interaction between CBZ and pressure-sensitive adhesive (PSA) was determined by Fourier Transform Infrared Spectroscopy (FT-IR). The influences of PSAs, penetration enhancers, patch thickness and drug content on the transdermal delivery of CBZ were studied thoroughly in vitro. Both CBZ releasing from patch and penetrating through the skin showed very great effect on the transdermal delivery of CBZ. The percentage of drug released from patch was increased with the decreasing of patch thickness, and so did the permeation percentage. The stratum corneum (SC) contributed approximately 57% resistance of total skin permeation resistance, and Span 20 increased the transdermal permeation by approximately 1.59-fold. The pharmacokinetic parameters were obtained through in vivo experiments of the optimized formulation using rabbit. Furthermore, the in vitro skin permeation results of CBZ patch correlated well with the in vivo absorption results in rabbit.     

Adhesive backing foil interactions affecting the elasticity,adhesion strength of laminates,and how to interpret these properties of branded transdermal patches

Standard tensile strength and peel adhesion tests were carried out to investigate interactions of pressure-sensitive adhesives (PSAs) with several backing foils used for transdermal patches. Seven branded transdermal patches (Alora, Cutanum, Estraderm MX 50, Estraderm TTS 50, Fem7 -50 micrograms, Menorest, Oesclim) were included in the investigation. Their skin adhesion measured in several clinical trials was compared with the results of the laboratory measurements according to PSTC-1 (Peel Adhesion for Single Coated Tapes 180 degrees Angle, Pressure Sensitive Tape Council, Illinois, 1996), such as Young's modulus at 3% elongation and peel adhesion to stainless steel. Data obtained for the PSA-coated backings (laminates) show increasing elasticity with increasing PSA thickness. Interactions of PSAs with backing foil became evident in significant changes in Young's modulus by low PSA thickness, as seen for the silicone adhesive. The Young's moduli of the laminates were found to be influenced not only by the elasticity of the backing foil but also by the chemical structure of the PSA. There was no correlation between the elasticity and peel adhesion of both the laminates and the branded patches. Likewise, for the branded patches the peel adhesion to stainless steel does not correlate with skin adhesion values obtained from clinical trials. The Young's modulus of the branded patches was between 4 N/mm2 (Oesclim) and 501 N/mm2 (Fem7). For the branded transdermal patches no correlation was found between Young's modulus and both the peel force on stainless steel and the skin adhesion reported in studies.     

Investigation of nanostructured lipid carriers for transdermal delivery of flurbiprofen

The aim of this study was to develop nanostructured lipid carriers (NLC) for transdermal delivery of Flurbiprofen (FP). The physical stability of FP-NLC and its in vitro permeation profile were investigated. After three months of storage at 4°C, 20°C, and 40°C, no significant differences between the evaluated parameters, such as pH value, the entrapment efficiency, particle size, and zeta potential were observed. In in vitro permeation studies, the cumulative permeated amounts and the release rate from FP-NLC were 412.53 ± 21.37 μg/cm² and 35.25 μg/cm²/h after 12 h (n = 6), respectively, while from saturated FP-PBS (pH = 7.4) were 90.83 ± 8.67 μg/cm² and 6.99 μg/cm²/h, respectively. These results indicated that the FP-NLC were with good physical stability and were able to improve the permeated amounts and the release rate of FP. It could potentially be exploited as a carrier with improved drug entrapment efficiency and permeated amount in the transdermal delivery of FP.     

Piroxicam benzoate--synthesis,HPLC determination,and hydrolysis

An improved method of piroxicam benzoate synthesis was described, and an isocratic reversed-phase high-performance liquid chromatography method for its determination was developed and fully validated. The method was found to be specific, precise (relative standard deviation 0.3%), accurate (mean recovery 99.9%), and robust. Limit of detection was estimated at 0.055 µg mL^-1 and limit of quantification at 0.185 µg mL^-1. The kinetics of piroxicam benzoate hydrolysis in aqueous buffer solutions (pH 1.1 and 10), simulated gastric and intestinal fluids was studied. The hydrolysis followed first-order kinetics. The following rate constants were obtained at pH 10: k = 1.8 × 10^-3 hr^-1 at 37°C and k = 3.4 × 10^-2 hr^-1 at 60°C. In acidic media, no significant hydrolysis was observed after 24 hr. During the 24-hr period in simulated intestinal fluid, only 10.9% of the starting ester was hydrolyzed.     

Stability indicating HPTLC determination of linezolid as bulk drug and in pharmaceutical dosage form

A simple, selective, precise, and stability-indicating high-performance thin layer chromatographic method of analysis of Linezolid both as a bulk drug and in formulations was developed and validated in pharmaceutical dosage form. The method employed TLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of toluene-acetone (5:5, v/v). This system was found to give compact spots for Linezolid (R_f value of 0.29 ± 0.01). Linezolid was subjected to acidic, alkali hydrolysis, oxidation, and photodegradation. The degraded products also were well separated from the pure drug. Densitometric analysis of Linezolid was conducted in the absorbance mode at 254 nm. The linear regression data for the calibration plots showed good linear relationship with r² = 0.997 ± 0.001 in the concentration range of 300-800 ng/spot. The mean value of correlation coefficient, slope, and intercept were 0.998 ± 0.003, 0.15 ± 0.009, and 19.52 ± 1.66 respectively. The method was validated for precision, accuracy, ruggedness, and recovery. The limits of detection and quantification were 20 ng/spot and 50 ng/spot, respectively. The drug undergoes degradation under acidic and basic conditions, oxidation and photo degradation. All the peaks of degraded product were resolved from the standard drug with significantly different R_f values. This indicates that the drug is susceptible to acid-base hydrolysis, oxidation, and photo degradation. Statistical analysis proves that the method is reproducible and selective for the estimation of the said drug. Because the method could effectively separate the drug from its degradation products, it can be used as a stability indicating one.     

Preparation, evaluation, and NMR characterization of vinpocetine microemulsion for transdermal delivery

A novel microemulsion was prepared to increase the solubility and the in vitro transdermal delivery of poorly water-soluble vinpocetine. The correlation between the transdermal permeation rate and structural characteristics of vinpocetine microemulsion was investigated by pulsed field gradient nuclear magnetic resonance (PFG-NMR). For the microemulsions, oleic acid was chosen as oil phase, PEG-8 glyceryl caprylate/caprate (Labrasol®) as surfactant (S), purified diethylene glycol monoethyl ether (Transcutol P®) as cosurfactant (CoS), and the double-distilled water as water phase. Pseudo-ternary phase diagrams were constructed to obtain the concentration range of each component for the microemulsion formation. The effects of various oils and different weight ratios of surfactant to cosurfactant (S/CoS) on the solubility and permeation rate of vinpocetine were investigated. Self-diffusion coefficients were determined by PFG-NMR in order to investigate the influence of microemulsion composition with the equal drug concentration on their transdermal delivery. Finally, the microemulsion containing 1% vinpocetine was optimized with 4% oleic acid, 20.5% Labrasol, 20.5% Transcutol P, and 55% double-distilled water (w/w), in which drug solubility was about 3160-fold higher compared to that in water and the apparent permeation rate across the excised rat skin was 36.4 ± 2.1 µg/cm²/h. The physicochemical properties of the optimized microemulsion were examined for the pH, viscosity, refractive index, conductivity, and particle size distribution. The microemulsion was stable after storing more than 12 months at 25°C. The irritation study showed that the optimized microemulsion was a nonirritant transdermal delivery system.     

Effect of urea and pantothenol on the permeation of progesterone through excised rat skin from polymer matrix systems

Standard in vitro permeation experiments, using excised rat skin, were carried out to establish the release profile and permeation behavior of progesterone from polymethacrylate (PMA), polyvinylpyrrolidon (PVP), and polyvinylalcohol (PVA) transdermal systems. Data obtained show significant differences in release characteristics from each polymer systems. The greatest amount of progesterone was released from the PVA system. The influence of urea and pantothenol on progesterone release was also investigated. Release data were compared with the permeation rates of progesterone across excised rat skin. The highest permeation rates were measured from PVA matrices containing 5% urea (860 ± 138 μg/cm²; cumulative amount permeated in 24 hr) and from PVP matrices containing 6% pantothenol (660 ± 73 μg/cm²; cumulative amount permeated in 24 hr). A good correlation between release and permeation data was found with the polymer matrices; however, this was not the case when additives were included.     

Effect of heat on characteristics of chitosan film coated on theophylline tablets

The effect of heat on the characteristics of chitosan film coated on theophylline tablets was studied. Chitosan of high viscosity grade with molecular weight in the range of 800,000-1,000,000, 80-85% degree of deacetylation was used as a film former by dissolving in 1% v/v acetic acid solution. The coated tablets had been cured at 40, 60, and 100°C for 6, 12, and 24 hr. The morphology of the film at the edge and surface of coated tablets was investigated using scanning electron microscopy. Film cracking was increased and clearly observed in the coated tablets cured at 100°C for 24 hr. As a result, more water could be absorbed into the tablets, followed by faster disintegration and faster drug release. The evidence of partial conversion of chitosonium acetate to chitin in the ¹³C nuclear magnetic resonance (NMR) spectra of chitosan films cured at 40, 60, and 100°C was observed, but it had no effect on drug release behavior. Theophylline tablets coated with chitosan films gave sustained release behavior in various media, i.e., distilled water, 0.1 N hydrochloric acid, pH 4.5 acetate buffer, and pH 6.8 phosphate buffer. In addition, the film coating temperature at 55-60°C and curing process at 40 and 60°C had no effect on the drug release from theophylline tablets coated with chitosan polymer. Finally, it might be concluded that both the physical and chemical properties of chitosan films were affected by heat.