Formulation and pharmacokinetic study of ranitidine hydrochloride suppositories

ABSTRACT

The present work is an extension of previous effect of certain excipients on the bioavailability of ranitidine hydrochloride. It was concluded that sodium sulphate ranitidine hydrochloride mixture in ratio 11 in both physical and coground mixtures are the excipient of choice for overcoming the hygroscopic nature of ranitidine. Also, statistical analysis of the pharmacokinetic data revealed that coground mixture gave more relative bioavailability than the physical mixture. Influence of the hydrophobicity of different fatty suppository bases on the dissolution profile of ranitidine hydrochloride coground mixture was studied. Witepsol W[25], W[3], and W[35] either single base or blends in [11] w/w ratio were used as hydrophobic suppository bases. Weight variation, content uniformity, hardness and melting range tests were conducted on the formulations. In vitro release was carried out according to USP basket method. Shelf storage of bases showing the highest drug release namely Witepsol W[25], W[25]+W[35], W[25]+W[31], showed no significant change in the drug release. Witepsol W[25] was subjected to in-vivo availability study as representative of the most promising formula according to the in vitro release data. The in-vivo availability and pharmacokinetic studies of the selected formula as well as on the oral administration of commercial product and coground mixture to act as reference product revealed that for practical use the dose of suppositories should be 60% of the oral dose of coground mixture according to AUC[0-6] values