Transbuccal delivery of chlorpheniramine maleate from mucoadhesive buccal patches.

This article describes buccal permeation of chlorpheniramine maleate (CPM) and its transbuccal delivery using mucoadhesive buccal patches. Permeation of CPM was calculated in vitro using porcine buccal membrane and in vivo in healthy humans. Buccal formulations were developed with hydroxyethylcellulose (HEC) and evaluated for in vitro release, moisture absorption, mechanical properties, and bioadhesion, and optimized formulation was subjected for bioavailability studies in healthy human volunteers. In vitro flux of CPM was calculated to be 0.14 +/- 0.03 mg.h(-1).cm(-2) and buccal absorption also was demonstrated in vivo in human volunteers. In vitro drug release and moisture absorbed were governed by HEC content and formulations exhibited good tensile and mucoadhesive properties. Bioavailability from optimized buccal patch was 1.46 times higher than the oral dosage form and the results showed statistically significant difference.

Development of carvedilol transdermal patches: evaluation of physicochemical, ex vivo and mechanical properties.

Monolithic matrix-type transdermal drug delivery systems for carvedilol were prepared using a film casting technique involving hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), Eudragit RS 100 (ERS 100), and Eudragit RL 100 (ERL 100) as matrix-forming polymers. The prepared transdermal drug delivery systems were extensively evaluated for in vitro release, ex vivo permeation through rat abdominal skin, moisture absorption, moisture content, water vapor transmission, stability, and mechanical properties. Formulations F2, F3, and F5 were composed of a 4:1 ratio of HPMC, ERS 100; HPMC, HPC; and HPMC, ERL 100, respectively, whereas F4, F6, and F7 were composed of 3:0.5:0.5 of HPMC, ERS 100, HPC; HPMC, HPC, ERL 100; and HPMC, ERS 100, ERL 100. Formulation F1 was composed of HPMC polymer. All formulations carried 8% v/w of d-limonene as a penetration enhancer and 20% v/w of dibutylphthalate as a plasticizer. The physicochemical interaction between carvedilol and polymers were investigated by Fourier transform infrared spectroscopy and differential scanning calorimetry. Formulation F5 showed both maximum drug release (12.31 mg) and permeation (2987.67 microg/cm2) in 24 h, which differed significantly (P < 0.05) among all the formulations. Formulation F5 showed maximum flux (32.80 microg/h/cm2), which meets the flux requirements, and differed significantly (P < 0.05) among all the formulations with a permeation coefficient of 0.82 x 10(-2) cm/h. Fourier transform infrared spectroscopy and differential scanning calorimetry studies showed no evidence of interaction between the drug and polymers. The formulations mechanical properties, tensile strength and elastic modulus (5.89 kg/cm2 for formulation F5) reveal that they are strong but not brittle. A shelf life of 2 years was predicted for the transdermal drug delivery systems. Carvedilol monolithic matrix-type transdermal therapeutic systems could be prepared having both the required flux and suitable mechanical properties.

In vitro permeation of carvedilol through porcine skin: effect of vehicles and penetration enhancers.

This investigation studied the effect of vehicles on the in vitro permeation of carvedilol from saturated solutions across porcine skin and selected appropriate penetration enhancers. Labrasol, Transcutol, polyethylene glycol 400, propylene glycol, ethanol, oleic acid, isopropyl myristate, and phosphate buffered saline (pH 7.4) containing 40% v/v polyethylene glycol 400 as control, were used as vehicles; limonene, carvone, camphor, menthol, Transcutol, and Labrasol at 5% w/v concentrations were used as penetration enhancers. Skin permeation studies were conducted in Franz diffusion cells using excised porcine ear skin. Solubility was highest (369.13 mg/mL) in Transcutol, whereas isopropyl myristate showed the lowest solubility (0.79 mg/mL) among all the vehicles. The flux of carvedilol from Transcutol, Labrasol, polyethylene glycol 400, ethanol, and oleic acid was 10.5, 8.6, 4.2, 2.9, and 1.5 times higher, respectively, than that observed with control. The flux obtained using Transcutol was significantly higher (P < 0.05) than the flux obtained using the other vehicles. However, the flux values of carvedilol using isopropyl myristate (P < 0.01) and propylene glycol (P < 0.05) were significantly lower than that of the control. Solutions containing 5% w/v camphor showed maximum permeation (232.54 microg) in 24 h with a flux of 3.19 microg/cm2/h, which was significantly different (P < 0.05) than the flux obtained using other permeation enhancers. The control sample showed lowest permeation (30.50 microg), with a flux of 0.33 microg/cm2/h. The flux of carvedilol from the solutions containing 5% w/v camphor, limonene, Transcutol, carvone, Labrasol, and menthol were 9.7, 7.6, 7.6, 6.3, 4.7, and 2.3 times higher, respectively, than that observed using the control. The present study suggests that Transcutol, Labrasol, and polyethylene glycol 400 may be used as potential vehicles and camphor, limonene, and Transcutol at a 5% w/v level as penetration enhancers.

Development of mucoadhesive patches for buccal administration of carvedilol.

A buccal patch for systemic administration of carvedilol in the oral cavity has been developed using two different mucoadhesive polymers. The formulations were tested for in vitro drug permeation studies, buccal absorption test, in vitro release studies, moisture absorption studies and in vitro bioadhesion studies. The physicochemical interactions between carvedilol and polymers were investigated by Fourier transform infrared (FTIR) Spectroscopy. According to FTIR the drug did not show any evidence of an interaction with the polymers used and was present in an unchanged state. XRD studies reveal that the drug is in crystalline state in the polymer matrix. The results indicate that suitable bioadhesive buccal patches with desired permeability could be prepared. Bioavailability studies in healthy pigs reveal that carvedilol has got good buccal absorption. The bioavailability of carvedilol from buccal patches has increased 2.29 folds when compared to that of oral solution. The formulation AC5 (HPMC E 15) shows 84.85 + 0.089% release and 38.69 + 6.61% permeated through porcine buccal membrane in 4 hr. The basic pharmacokinetic parameters like the C(max), T(max) and AUC(total) were calculated and showed statistically significant difference (P<0.05) when given by buccal route compared to that of oral solution.

Development of nitrendipine transdermal patches: in vitro and ex vivo characterization.

OBJECTIVE: The aim of the investigation was to develop and evaluate matrix type transdermal drug delivery systems (TDDS) of nitrendipine (NTDP). EXPERIMENTAL: The matrix type TDDS of NTDP were prepared by solvent evaporation technique. Ten formulations (composed of Eudragit RL 100 and Hydroxypropyl methyl cellulose in the ratios of 5:0, 4:1, 3:2, 2:3, 1:4 in formulations A1, A2, A3, A4, A5 and Eudragit RS 100 and Hydroxypropyl methyl cellulose in the same ratios in formulation B1, B2, B3, B4, B5 respectively) were prepared. All formulations carried 6 % v/w of carvone as penetration enhancer and 15% v/w of propylene glycol as plasticizer in dichloromethane and methanol as solvent system. The prepared TDDS were evaluated for in vitro release, ex vivo permeation, moisture absorption, moisture content and mechanical properties. The physicochemical interactions between nitrendipine and polymers were investigated by Fourier Transform Infrared (FTIR) Spectroscopy. RESULTS: The maximum drug release in 24 hrs for A series formulations was 89.29% (A4) and 86.17% for B series (B5), which are significantly (p < 0.01) different to the lowest values (57.58 for A1 and 50.64 for B1). Again formulations A4 (flux 23.51 microg/hr/cm(2)) and B5 (flux 22.98 microg/hr/cm(2)) showed maximum skin permeation in the respective series. The flux obtained with formulation A4 and B5 meets the required flux (19.10 microg/hr/cm(2)). The mechanical properties, tensile strength, elastic modulus (3.42 kg/mm(2) for A4 and 4.25 kg/mm(2) for B5) reveal that the formulations were found to be strong but not brittle. FTIR studies did not show any evidence of interaction between the drug and the polymers. CONCLUSION: Nitrendipine matrix type transdermal therapeutic systems could be prepared with the required flux having suitable mechanical properties.