Mucoadhesive delivery systems. II. Formulation and in-vitro/in-vivo evaluation of buccal mucoadhesive tablets containing water-soluble drugs.

From the previous work (Part I), mucoadhesive formulae containing 5% CP/65% HPMC/30% lactose and 2% PC/68% HPMC/30% mannitol as well as formulae based on sodium carboxymethyl cellulose (SCMC) were selected. Medicated tablets were prepared using diltiazem hydrochloride (DZ) and metclopramide hydrochloride (MP) in two different doses (30 and 60 mg). The effect of drug and dose on the mucoadhesive properties and in-vitro drug release was evaluated. All formulae produced extended drug release (over 8 to 12 h). Polyacrylic acid based matrices (PAA) showed Fickian's diffusion release pattern for both drugs. SCMC ensured zero-order release for DZ, which deviated to anomalous behavior in case of MP. Doubling the dose significantly reduced the bioadhesion strength (p<0.05) with a slight improvement in drug release rate. The formulation of bilayer tablets containing drug-free layer and medicated layer enhanced the drug release without affecting the bioadhesive performance. The bilayer tablet formulated with 2% PC/68% HPMC/30% mannitol (PC2) was selected for studying the in-vivo metoclopramide release in four healthy volunteers. The tablet ensured controlled drug release for 12 h, in addition, good correlation (r=0.9398) was observed between in-vitro and in-vivo data. The effect of ageing on selected formulae containing DZ and MP, respectively, was studied. Storage at 40 degrees C and 75% relative humidity for 6 months didn't influence the mucoadhesive performance, however, an enhanced released rate was observed.