Preparation and characterization of pyrimethamine solid dispersions and an evaluation of the physical nature of pyrimethamine in solid dispersions

摘要

The objective of this investigation was to prepare, characterize pyrimethamine solid dispersions formulated with different carriers and to evaluate the physical nature of pyrimethamine in solid dispersion. Pyrimethamine solid dispersions were prepared by solvent evaporation technique using a rotary evaporator and characterized using intrinsic dissolution studies, differential scanning calorimetry (DSC), x-ray diffractometry (XRD), fourier transform infrared spectroscopy (FTIR), dissolution studies, and stability studies of selected solid dispersion. To further investigate the nature of drug, nuclear magnetic resonance was also performed. Intrinsic dissolution studies demonstrate that the dissolution rate of pyrimethamine could be markedly improved via solid dispersion technique. DSC studies show that PEG 6000 and poloxamer 188 could dissolve pyrimethamine up to 50% (w/w) in molten state. Results of XRD and FTIR suggest the presence of a different polymorphic form of pyrimethamine which might be due to the disruption of the supramolecular ribbon (synthon) formation of the original pyrimethamine polymorph. Significant improvement in dissolution rate from pyrimethamine solid dispersion using poloxamer 188 was achieved and pyrimethamine/poloxamer 188 ratio at 1:3 showing maximum dissolution rate enhancement of pyrimethamine. Furthermore, stability studies indicate no significant change in the physical nature of pyrimethamine in selected solid dispersion up to 5-month.