| In vitro and in vivo Evaluation of Floating Controlled Release Dosage Forms of Verapamil Hydrochloride Seham A. Elkheshen*, Alaa Eldeen B. Yassin, Saleh Alsuwayeh, and Fayza A. Alkhaled Department of Pharmaceutics, Collage of Pharmacy, King Saud University, Riyadh (Saudi Arabia) * Present address: see address for correspondence
The present work investigates the preparation of sustained release floating systems for verapamil hydrochloride using different hydrocolloid polymers including hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), ethylcellulose (EC) and Carbopol (CP). Floating was achieved by adding an effervescent mixture of sodium bicarbonate and anhydrous citric acid. Some factors were investigated concerning their effect on flotation and rate of drug release including the drug to polymer ratio, the granulating agents, the incorporation of release retardant, coating granules with ethyl cellulose, and finally granule-com-pression into tablets.
A formula composed of 1:1 of verapamil to HPMC, 5 % of gas generating mixture and prepared by wet granulation with 96% alcohol followed by compression was chosen for in-vivo evaluation in comparison with a commercial controlled release product of verapamil hydrochloride. Investigations have been undertaken in beagle dogs to evaluate both the intragastric retention performances using X-ray and the bioavailability of the drug from both test and standard tablets. Results showed that for powderblend filled into capsules, only HPMC-4000 formulations combined a good floating and reasonable delay in drug release. However granulation of the same formulations led to complete loss of both the floating and the sustained release characteristics. Tableting of granules containing various verapamil:HPMC-4000 ratios showed excellent buoyancy and slow release profile. Results also revealed that floatation was able to delay the gastric emptying of verapamil tablet in beagle dogs for more than four hours compared to almost one hour for a control tablet devoid of the gel forming polymer and the gas generating mixture. The floating tablets showed bioequivalence with a commercial sustained release tablet with higher mean AUC0- and Cmax and longer tmax, however, nonsignificantly different.
Key words Buoyancy dosage forms • Floating dosage forms • Gastroretentive dosage forms • Hydrodynamically balanced systems • Hydrophilic matrix polymers • Verapamil hydrochloride |
