Oral sustained-release bioadhesive tablet formulation of didanosine.
The objective of this study was to formulate a hydrogel-forming bioadhesive drug delivery system for oral administration of didanosine (ddI). The aim of this tablet dosage form is to improve the oral absorption of ddI by delivering it in small doses over an extended period and localizing it in the intestine by bioadhesion. Compressed tablets of ddI using Polyox WSRN-303, Carbopol 974P-NF, and Methocel K4M as the bioadhesive release rate-controlling polymers were prepared. The effect of polymer concentration on the release profile and in vitro bioadhesion of the matrix tablets was studied. Tablet formulations with Polyox WSRN-303 (10%) and Methocel K4M (30%) showed 93 and 90% drug release, respectively, after 12 h. The drug release was found to be linear when fitted in the Higuchi equation (square-root time equation), suggesting zero-order release. Carbopol 974-P-NF was found to inhibit the complete release of ddI because of drug-polymer interaction; hence, is not suitable for formulation of ddI. Drug diffusion and swelling of the polymer (anomalous Fickian release) was found dominant in ddI release. In general, in vitro bioadhesion increased with an increase in polymer concentration. Tablets containing a single polymer can be designed to form hydrogels serving the dual purpose of bioadhesion and sustained release.
Betageri
G V
GV
Western University of Health Sciences, Pomona, California 91766, USA. gbetageri@westernu.edu
Deshmukh
D V
DV
Gupta
R B
RB
D000269:Adhesives; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D016049:Didanosine / Q000008:administration & dosage*; D005079:Excipients; D006207:Half-Life; D007785:Lactose / Q000031:analogs & derivatives*; D008747:Methylcellulose / Q000031:analogs & derivatives*; D010078:Oxazines; D012995:Solubility; D013607:Tablets
D000269:Adhesives; D019380:Anti-HIV Agents; D003692:Delayed-Action Preparations; D005079:Excipients; D010078:Oxazines; D013607:Tablets; D008747:Methylcellulose; C071191:MK 458; D007785:Lactose; D016049:Didanosine