Buccal Drug Delivery System of Risperidone- Formulation and in Vitro, in Vivo Evaluation

Abstract

Bio-adhesive buccal-delivery of drugs is one of alternative to the oral route of drug administration, particularly drugs that are having poor-bioavailability (BA) a first pass effect. The bioavailability of such drugs may be significantly improved if delivered through the buccal route. Risperidone is used widely for treating hypertension. The drug is well absorbed from the gastrointestinal tract but its bioavailability is low (30- 50%) due to extensive first pass metabolism. Since the buccal route bypasses the first-pass effect, the dose of Risperidone could be reduced by 50%. The physicochemical properties of Risperidone, its suitable half-life (3 7 h) a low molecular weight (196.64) used the oral route for small dose. Risperidone buccal muco-adhesive tablets were prepared by direct compression technique, using carbopol 934P, HPMC K4M as muco-adhesive polymers. Prepared formulations were evaluated for physicochemical characteristics, ex-vivo residence time a in-vitro release studies. Further, in vivo pharmacokinetic studies were performed in pigs. The results of all the prepared tablets were within the acceptable pharmacopeial limits. The swelling a bio adhesive strength values were increased a drug-release (DR) was decreased with increasing the polymer concentration. From the results, tablets with Na CMC (F2) exhibited better release, which may be due to the hydrophilicity a water uptake by the tablet a were considered as optimized formulation. The optimized formulation F2 developed with HPMC K4M released 99.62±2.24% in 6 h. The release mechanism from kinetic methods suggests that, the drug-release (DR) follows zero-order kinetics with diffusion mechanism. The drug permeation was found to be 89.88%, while the flux a permeability coefficient of risperidone was calculated to be 0.668 mg h−1 cm−2 a 0.056 cm h−1, respectively.  DSC studies confirming that there was no interaction between the drug and other excipients.3.09-folds enhance bio-adhesive in the oral bioavailability (BA) of risperidone from buccal tablet when compared with immediate release marketed formulation (Nepresol®). Thus, the buccal tablets of Risperidone showed enhanced BA a which was confirmed by in-vivo studies.