The influence of povidone K17 on the storage stability of solid dispersions of nimodipine and polyethylene glycol.

摘要

Previous studies revealed that solid dispersions containing nimodipine and polyethylene glycol 2000 can be effectively prevented from recrystallization by adding povidone K17. These systems are characterized by a high dissolution rate and a remarkable supersaturation of the drug in the dissolution media. It is still unknown if these characteristics are achievable with all polyethylene glycol and povidone mixtures. The objective of the present study is to find out, whether povidone K17 has to be dissolved in melted polyethylene glycol during the preparation process of solid dispersions by the melting method in order to avoid recrystallization of the drug and to ensure storage stability. Solid dispersions consisting of 20% (m/m) nimodipine, 16% (m/m) povidone K17 and 64% (m/m) of six different mixtures of polyethylene glycol 2000 and 8000 were prepared by the melting method and investigated by dissolution testing, thermal analysis and X-ray diffraction. As the solubility of povidone K17 in polyethylene glycol 2000 is about 70% at 65 degrees C and decreases with increasing molecular weight of the polyethylene glycol, mixtures containing different amounts of dissolved povidone K17 are obtained by varying the mixing ratio of polyethylene glycol 2000 and 8000. Recrystallization is inhibited in the formulations, containing mainly polyethylene glycol 2000 whereas recrystallization occurs in systems consisting predominantly of polyethylene glycol 8000. These results show clearly that dissolution of povidone in melted polyethylene glycol is a prerequisite in order to prevent recrystallization.