Wissenschaft und Technik: Driginale In vitro and in vivo Evaluation of Floating Controlled Release Dosage Forms of Verapamil Hydrochloride Seham A. Elkheshen*, Alaa Eldeen B. Yassin, SaIeh Alsuwayeh, and Fayza A. AlkhaIed Department of Pharmaceutics, Collage of Pharmacy, King Saud University, Riyadh (Saudi Arabia) • Present address: see address for correspondence Summary 1364 Elkheshen et al. - Verapamil hydrochloride The present work investigates the pre- paration of sustained release floating systems for verapamll hydrochloride using different hydrocolloid polymers in- cluding hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), ethylcellulose (EC) and Carbopol (CP). Floating was achieved by adding an effer- vescent mixture of sodium bicarbonate and anhydrous citric acid. Some factors were investigated concerning their effect on flotation and rate of drug release in- cluding 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 verapa- mil to HPMC, 5 % of gas generating mix- ture and prepared by wet granulation with 96% alcohol followed by compres- sion was chosen for in-vivo evaluation in comparison with a commercial con- trolled release product of verapamll hy- drochloride. Investigations have been un- dertaken in beagle dogs to evaluate both the intra-gastric retention performances using X-ray and the bioavallabllity of the drug from both test and standard tablets. Zusammenfassung Untersuchung von flotierenden Formulle- rungen zur kontrolllerten Freisetzung von Verapamll-Hydrochlorid in vitro und in vivo Untersuchungen ilber die Zubereitung flotierender Systeme ffir die verzOgerte Freisetzung von Verapamil-Hydrochlorid werden beschrieben; verschledene Hydro- kolloid-Polymere einschlieBllch Hydroxy- propylmehtylcellulose (HPMC), Hyroxy- propylcellulose, Ethylcellulose und Car- hopol wurden eingesetzt. Flotation wurde durch den Zusatz einer gasbildenden MI- schung von Natrlumbicarhonat und was- serfreier Zltronensaure erreicht. Einige Results showed that for powder-blend filled into capsules, only HPMC-4000 for- mulations combined a good floating and reasonable delay in drug release. How- ever granulation of the same formula- tions led to complete loss of both the floating and the sustained release charac- teristics. Tableting of granules containing various verapamil:HPMC-4000 ratios showed excellent buoyancy and slow re- lease prome. 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 AUCo~ and Cm~ and longer 1m~, however, non-significantly different. Faktoren mit EinfluB auf Flotation und Wirkstofffreisetzung wurden untersucht, u. a. Wirkstoff-Polymer-VerhaIU1is, Gra- nuliermittel, Zusatz von frelsetzungsver- wgernden Mlttein, Oberzlehen der Gra- nula mit Ethylcellulose, Verpressen des Granulates zu Tabletten. Filr die In-vivo-Priifung Im Vergleich mit einem kommerziell erhaItlichen Ver- apamll-Hydrochlorid-Produkt mit kon- trollierter Freisetzung wurde eine Formu- lierung ausgewahlt, die Verapamil und HPMC Im VerhaItnls 1:1 sowie 5 % gas- bildende Agentlen enthaIt, mit 96 % Alko- hol na~ granullert und anschlie~nd ver- preBt wurde. Von beiden Priiparaten Phnnn. Ind. 66, Nr. t 1, 1364-1372 (2004) e ECV . Editio Cantor Verlag, Aulendorf (Germany)