Gelucire 39/01 as excipient for gastroretentive metronidazole sustained delivery

Gelucires (54/02, 43/01) have been used in preparation of floating sustained release formulations to prolong gastric residence time and increase its bioavailability. In this type of formulations Methocel K100M CR has been used as a swelling as well as a release-retarding polymer. The objective of this study was to explore the application of Gelucire 39/01 for the design of sustained release multi-unit and single-unit floating systems of metronidazole. Metronidazole-Gelucire 39/01 granules were prepared by melt granulation technique, alone and after addition of hydroxypropylmethylcellulose K15M (HPMC) or sodium cross-linked carboxymethylcellulose (Carmacel). The formulations were evaluated in vitro for their floating ability and drug release. Increasing proportions of Gelucire decrease the initial fast release of the drug that stabilizes and practically come to an end thereafter. The granules floating times were greater than 6 hours. The addition of HPMC and Carmacel increase the drug release that stabilizes after 2 hours. The use of single-unit systems (tablets) allowed a more gradual drug release. Carmacel formulations showed a span of drug dissolved after 3 hours ranging from 20 mg to 495 mg, with a trend to stabilize after 3 hours while HPMC formulations showed a range from 16 mg to 156 mg and a trend to increase the drug release. HPMC tablets floated more than 3 hours while Carmacel tablets showed no floatability. Gelucire 39/01, can be considered as a carrier for design of floating drug delivery systems only when mixed with dissolution enhancers that increase the permeability of the almost impermeable wax matrix.