Purnima D. Amin

The objective of the study was preparation of sustained release matrix tablets by hot melt extrusion (HME) and process optimization for continuous manufacturing. Furthermore, HME tablets were evaluated with respect to in vitro release rate, erosion behavior and water uptake study. Hydroxypropylcellulose (HPC) was used as release retarding polymer. The drug chosen for study was first line anti tuberculosis drug rifampicin. 50 % drug loaded HME tablets were prepared. The HME tablets were characterized by DSC, FTIR and SEM. No chemical interaction was found between drug and polymer as per DSC and FTIR. Dispersion of drug particles and internal micro pores was observed by SEM. In vitro release study revealed 50% drug loaded HPC matrix tablets gave sustained release of 101.41±1.02% at the end of 24 h. Release rate of rifampicin from HME tablets was found to be dependent on the concentration of polymers and plasticizer. The release rate from the edges and circumference of tablets suggested the hydration of the tablets from the circumference was more significant than at edges of the tablets. Drug release from HME matrix tablets was found to follow Super case-II transport mechanism. HME tablets were stable for six months as per ICH guideline.

The objective was to enhance the solubility and dissolution rate of Artemether poorly water soluble antimalarial, by the preparation of solid dispersion (SD) granules. The dispersion granules were prepared using a hot melt granulation technique which involved the preparation of a homogenous dispersion of ARTM in surfactant melt, followed by its adsorption onto the surface of AEROPERL® 300 Pharma, an inert absorbent using the solvent evaporation method. The dispersion granules were characterized for their in-vitro dissolution rate, moisture content and flow properties. The formulation was further characterized by FTIR,DSC, XRD and SEM analysis. FTIR spectrum revealed some drug excipient interactions. DSC and XRD data indicated the retention of amorphous form of ARTM. SEM confirmed the homogeneity and surface adsorption of the ARTM-Lutrol F127 or ARTM-Lutrol F68 melt on AEROPERL® 300 Pharma leading to an enhanced surface area and thus the dissolution rate. The optimized dispersion granules were filled inside the capsules and evaluated. The in-vitro dissolution rate of these capsules was significantly better in comparison with pure drug. Physical characterisation enabled us to understand the effects of formulation variables on the dispersion granules of ARTM.