Book Description

The objective of this project was to improve the solubility of two poorly water soluble drugs, namely indomethacin and phenytoin by formulating ternary solid dispersions with a carrier and an adsorbent. Urea was used as the dispersing agent for indomethacin, while Kollidon®VA64 was used for both indomethacin and phenytoin. Solid dispersions with urea and indomethacin were prepared by the hot melt method while the ones with Kolllidon®VA64 were prepared by the solvent extraction method. Various techniques were used to characterize the solid dispersions, immediately after they were made and after two months of elevated temperature and relative humidity, including Differential Scanning Calorimetry (DSC), X-Ray Powder Diffraction (PXRD), Scanning Electron Microscopy (SEM) and in vitro dissolution studies. The DSC data showed thermograms for all the ingredients, physical mixtures and solid dispersions. It indicated that the physical mixtures tend to have the drugs in their crystalline form. However, the solid dispersions gave formulations that were completely amorphous. PXRD studies confirmed these results. PXRD results for the drugs show their crystalline nature which could not be seen with the solid dispersions. It also confirmed that the formulations were stable over the two month period when they were kept at elevated temperature and controlled relative humidity conditions. SEM images indicated that the solid dispersion of the drug and carrier were coated on the Nuesilin®US2 well, showing it was possible to coat the solid dispersion on the Nuesilin®US2 by both the fusion method and solvent extraction method . In vitro dissolution studies reveal that there is an increase in both the quantity of drug solubilized and the rate of dissolution after formulation into their solid dispersions. The stability studies for two months under various temperatures (300C, 350C, 400C, and 450C) and relative humidity conditions (100%, 75.29 ±0.12%, 54.38 ±0.23 and 23.11 ±0.25% RH) indicated that the formulations might be stable. It also indicated that as the quantity of drug in the formulations increased, there was a tendency for some formulations to be unstable. The accelerated stability studies also helped to determine the trends with the shelf life of the formulations using the Arrhenius equation. It also gave some idea about the tendency of relative humidity to affect the degradation rate of the drug.