Enhanced Bioavailability of Nimodipine from Bioadhesive Buccal Bilayered Patches in Human Volunteers.

Aims: The objective of the present study was to develop a bioadhesive bilayered buccal patch of Nimodipine (15 mg) using Eudragit Rs 100 as secondary layer and a primary layer with Hydroxy propyl methyl cellulose and Hydroxy propyl cellulose JF. Methodology: Bilayered buccal patches were prepared by solvent casting technique. The absence of physiochemical interactions between NMDP and the polymer were investigated by differential scanning calorimetry (DSC). Bilayered buccal patches of NMDP were evaluated for in vitro drug permeation through porcine buccal membrane, in vitro drug release, moisture absorption, surface pH, mechanical properties and in vitro bioadhesion. Results: The results indicated that suitable bioadhesive bilayered buccal patches with desired permeability could be prepared. The bioavailability study was performed in healthy humans in a crossover experimental design. Bioavailability studies revealed that nimodipine possessed good buccal absorption. The relative bioavailability of the optimized buccal patch was found to be 205% in comparison to 30 mg marketed oral tablet. The formulation CC3 showed 68.84 ± 1.4% release and 46.85 ± 5.1% of drug permeated through porcine buccal membrane in 4 hr. A good correlation was seen between percentage in vitro release the extent of bioavailability for nimodine buccal patch. Conclusion: An improvement of bioavailability was obtained by buccal route to the extent of 2.05 times higher than that of oral route for NMDP. Hence, the development of a bioadhesive bilayered buccal patch for NMDP might be a promising one, as the necessary dose of drug could be decreased, resulting less side effects. Good ex vivo - in vivo correlation was obtained for NMDP.

Formulation of unidirectional release buccal patches of carbamazepine and study of permeation through porcine buccal mucosa

Objective:To achieve transbuccal release of carbamazepine by loading in unidirectional release mucoadhesive buccal patches. Methods:Buccal patches of carbamazepine with unidirectional drug release were prepared using hydroxypropyl methyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone and ethyl cellulose by solvent casting method. Water impermeable backing layer (Pidilite? Biaxially-oriented polypropylene film) of patches provided unidirectional drug release. They were evaluated for thickness, mass uniformity, surface pH and folding endurance. Six formulations FA2, FA8, FA10, FB1, FB14 and FB16 (folding endurance above 250) were evaluated further for swelling studies, ex vivo mucoadhesive strength, ex vivo mucoadhesion time, in vitro drug release, ex vivo permeation, accelerated stability studies and FTIR and XRD spectral studies. Results: The ex vivo mucoadhesion time of patches ranged between 109 min (FA10) to 126 min (FB14). The ex vivo mucoadhesive force was in the range of 0.278 to 0.479 kg/m/s. The in vitro drug release studies revealed that formulation FA8 released 84%and FB16 released 99.01%of drug in 140 min. Conclusions: The prepared unidirectional buccal patches of carbamazepine provided a maximum drug release within specified mucoadhesion period and it indicates a potential alternative drug delivery system for systemic delivery of carbamazepine.

Design and evaluation of tizanidine buccal mucoadhesive patches.

Mucoadhesive buccal dosage forms are becoming more popular and patient acceptable dosage forms. By this route advantages are many as the dose can be reduced, avoidance of first pass metabolism and liver toxicity, etc. The Tizanidine has first pass metabolism because of this the patient has to take more dose and two to three times in a day. To overcome this problem mucoadhesive patches of tizanidine are prepared and evaluated. Tizanidine is a non-selective, α-two adrenergic agonist receptor and used as muscle relaxant. The oral bioavailability of Tizanidine is 40%, because of first pass metabolism. The polymers used are polyvinyl alcohol and polyvinyl pyrolidine. FTIR and UV spectroscopic methods reveal that there is no interaction between tizanidine and polymers. The patches evaluated for various parameters and results are satisfied. In vitro release studies in phosphate buffer (pH, 6.6) exhibited drug release in the range of 71.68 to 97.27% in 90 min. The release of tizanidine from the patches followed first order, Higuchi’s model and mechanism diffusion rate limited. In vivo buccal absorption studies in rabbits showed 68.85% of drug releases from polyvinyl alcohol patch while it 67.52 to 88.31% within 90 min in human volunteers. Good correlation among in- vitro release and in- vivo studies observed.

Formulation and evaluation of mucoadhesive buccal patch of acyclovir utilizing inclusion phenomenon

Mucoadhesive buccal patch releasing drug in the oral cavity at a predetermined rate may present distinct advantages over traditional dosage forms, such as tablets, gels and solutions. A buccal patch for systemic administration of acyclovir in the oral cavity was developed using polymers hydroxy propyl methyl cellulose (K4M), hydroxy propyl methyl cellulose (K15M), sodium carboxy methyl cellulose and poly vinyl pyrolidone (K30), plasticizer poly ethylene glycol (400) and a backing membrane of Eudragit (RL100). The films were evaluated in terms of swelling, residence time, mucoadhesion, release, and organoleptic properties. The optimized films showed lower release as compared to controlled drug delivery systems. Hence, an inclusion complex of acyclovir was prepared with hydrophilic polymer hydroxylpropyl beta-cyclodextrin in the molar ratio of 1:1. The inclusion complex was characterized by optical microscopy, FAB mass spectroscopy, and FTIR spectroscopy. Patches formulated with the acyclovir inclusion complex were evaluated along the same lines as those containing acyclovir alone. The in vitro release data revealed a substantial increase from 64.35 percent to 88.15 percent in the case of PS I and PS II batches, respectively, confirming the successful use of inclusion complexes for the formulation of buccal patch of acyclovir.

Mucoadesivos bucais liberadores de fármacos para a cavidade oral com taxa de liberação pré-determinada podem apresentar distintas vantagens em relação às formas farmacêuticas convencionais como comprimidos, géis e soluções. Neste trabalho, um adesivo bucal para administração sistêmica de aciclovir através da cavidade oral foi desenvolvido empregando-se os polímeros hidroxipropilmetil celulose (K4M), hidroxipropilmetil celulose (K15M), carboximetil celulose sódica e polivinil pirrolidona (K30), polietilenoglicol plastificado (400) e uma membrana suporte de Eudragit (RL100). Os filmes obtidos foram avaliados em termos de intumescimento, tempo de residência, mucoadesão, liberação e propriedades organolépticas. Os filmes otimizados apresentaram liberação mais lenta em comparação a outros sistemas de liberação controlada. Desta maneira, um complexo de inclusão de aciclovir foi preparado com o polímero hidrofílico hidroxipropil beta-ciclodextrina em proporções molares 1:1. O complexo de inclusão foi caracterizado por microscopia ótica, espectrometria de massas FAB e espectroscopia FTIR. Os adesivos formulados com o complexo de inclusão de aciclovir foram avaliados em paralelo com adesivos contendo aciclovir isolado. Os dados de liberação in vitro revelaram um aumento substancial, de 64,34 por cento para 88,15 por cento, nos lotes PS I e PS II, respectivamente, confirmando o sucesso do uso de complexos de inclusão para a formulação de adesivos bucais de aciclovir.