ABSTRACT
The development of sustained release drug formulations enhances drug efficacy, improves patient compliance and reduces dosing frequency. Melt granulation is a simple cost-effective technique for modifying drug release. The aim of this study was to evaluate the effect of inclusion of a leaching agent on melt granules formed from shea butter and carnauba waxes using paracetamol as a model.
Methods: Different batches of melt granules of Paracetamol made using varying concentrations (2% – 10%w/w) of shea butter or carnauba wax, with or without sodium chloride as a leaching agent were prepared and encapsulated into hard gelatin capsules. In a similar manner, conventional granules were made with 15 % maize starch mucilage and encapsulated as control. The capsules were subjected to in-vitro dissolution studies, and at predetermined intervals, samples were withdrawn and analyzed spectrophotometrically at a wavelength of ⅄max. 296nm. The dissolution data obtained were analyzed to determine release kinetics and mechanism of drug release.
Results and Discussion: From the results of the in-vitro drug release studies from the melt granules and convectional granules, it was seen that the convectional granules released over 85% of its content within 50 minutes, while the melt granules exhibited a marked reduction in the release of its content over 4 hours. The maximum release was dependent on the fat content and type of fat in the melt granules. Therefore, the higher the fat content, the lower the amount of drug release and the more retarded the rate of release. Addition of salt to the melt granules brought about a marked increase in rate drug release from the melt granules.
Conclusion: The study showed that the melt granules from shea butter and carnauba waxes prolonged the time taken to release paracetamol compared to conventional granules and this was dependent on concentration of lipid hydrophobicity. The inclusion of sodium chloride as a leaching agent significantly enhanced drug release by creating micro pores within the wax matrix, this is thought to facilitate water penetration and drug diffusion out of the matrix. These findings highlight the potential of shea butter wax as model wax in formulation of controlled drug delivery systems. Again, this approach may be useful in the design of multi-unit dosage forms where immediate release will be achieved from convectional granules and sustained release of from melt granules.
