Sustained-Release Tablets of Hydrochlorothiazide, a Slightly Water-Soluble Molecule Using Glyceryl Behenate

Resumo

Hydrochlorothiazide (Hctz) is an antihypertensive drug acting as diuretic. In order to prolong the drug activity, various formulations of Hctz were developed. This work was aimed at developing a sustained-release formulation using glyceryl behenate (Compritol 888 ATO, C888) as a waxy retardant matrix and Hctz as the model of slightly water-soluble drug. Two different ratios of Hctz/C888 (1:1 and 1:2) were tried to determine if increasing the C888 fraction will retard the release of Hctz. Melt granulation and direct compression have been tested on the two ratios in order to identify which one is most effective to modify the release of Hctz. The results showed that the 1:2 ratio (Hctz 25 mg versus C888 50 mg) successfully retarded the dissolution of Hctz. On the other hand, hot fusion method was found to be more effective than compression of physical mixtures in retarding the drug dissolution from the matrix. Thus, formulations based on the appropriate matrix of Compritol 888 ATO can be used to produce prolonged-release tablets for slightly water-soluble drugs like Hctz.