Development of novel bioadhesive buccal formulation of diltiazem: in vitro and in vivo characterization.
The aim of the investigation was to develop and evaluate buccoadhesive tablets of diltiazem hydrochloride (DZH) using hydroxypropyl methyl cellulose (HPMC) K4M and Carbopol 934 as mucoadhesive polymers. Formulations A1, A2, A3, A4, and B1, B2, and B3, were composed of HPMC K4M and Carbopol 934 at ratios of 1:2, 1:3, 1:4, 1:5, and 1:1, 1:2, 1:3, respectively. The developed formulations were evaluated for physicochemical, in vitro drug release, in vitro adhesion and in vivo studies in healthy human volunteers. The buccal absorption study in healthy volunteers revealed that about 36.86% of the drug was absorbed. Formulation A3 showed maximum release in 8 h. As the concentration of polymer in the formulation increased, the drug release decreased. The bioavailability of diltiazem from buccoadhesive tablets was 1.57-fold higher than oral tablets. The basic pharmacokinetic parameters, C(Max), T(Max), and the area under the curve, were calculated and showed statistically significant difference (P < 0.05) when the drug was given by the buccal route compared to that of oral tablet. The results indicate that suitable bioadhesive buccal tablets with improved bioavailability could be prepared.
Centre for Biopharmaceutics and Pharmacokinetics, University College of Pharmaceutical Sciences, Kakatiya University, Warangal 506 009 (A.P.), India.
Shayeda
Ramesh
R
Gannu
Chinna Reddy
CR
Palem
Y Madhusudan
YM
Rao
D000042:Absorption; D000179:Acrylates / Q000737:chemistry; D000268:Adhesiveness; D000278:Administration, Buccal; D000328:Adult; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004110:Diltiazem / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D065347:Hypromellose Derivatives; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D009061:Mouth Mucosa / Q000378:metabolism*; D013552:Swine; D013607:Tablets; D055815:Young Adult
D000179:Acrylates; D002121:Calcium Channel Blockers; D004337:Drug Carriers; D013607:Tablets; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D004110:Diltiazem; C453622:carbopol 934P