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Effect of physical state and particle size distribution on dissolution enhancement of nimodipine/PEG solid dispersions prepared by melt mixing and solvent evaporation

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Effect of physical state and particle size distribution on dissolution enhancement of nimodipine/PEG solid dispersions prepared by melt mixing and solvent evaporation

Content Provider	PubMed Central
Author	Papageorgiou, George Z. Dimitrios, Bikiaris Karavas, Evagelos Politis, Stavros Aristides, Docoslis Park, Yong Stergiou, Anagnostis Georgarakis, Emmanouel
Abstract	The physical structure and polymorphism of nimodipine were studied by means of micro-Raman, WAXD, DSC, and SEM for cases of the pure drug and its solid dispersions in PEG 4000, prepared by both the hot-melt and solvent evaporation methods. The dissolution rates of nimodipine/PEG 4000 solid dispersions were also measured and discussed in terms of their physicochemical characteristics. Micro-Raman and WAXD revealed a significant amorphous portion of the drug in the samples prepared by the hot-melt method, and that saturation resulted in local crystallization of nimodipine forming, almost exclusively, modification I crystals (racemic compound). On the other hand, mainly modification II crystals (conglomerate) were observed in the solid dispersions prepared by the solvent evaporation method. However, in general, both drug forms may appear in the solid dispersions. SEM and HSM microscopy studies indicated that the drug particle size increased with drug content. The dissolution rates were substantially improved for nimodipine from its solid dispersions compared with the pure drug or physical mixtures. Among solid dispersions, those resulting from solvent coevaporation exhibited a little faster drug release at drug concentrations lower than 20 wt%. Drug amorphization is the main reason for this behavior. At higher drug content the dissolution rates became lower compared with the samples from melt, due to the drug crystallization in modification II, which results in higher crystallinity and increased particle size. Overall, the best results were found for low drug content, for which lower drug crystallinity and smaller particle size were observed.
Related Links	http://dx.doi.org/10.1208/aapsj080471
Starting Page	623
File Format	PDF
ISSN	15507416
e-ISSN	15507416
Journal	The AAPS Journal
Issue Number	4
Volume Number	8
Language	English
Publisher	Springer-Verlag
Publisher Date	2006-12-01
Access Restriction	Open
Rights Holder	Springer-Verlag
Subject Keyword	Pharmaceutical Science Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmaceutical Science

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Effect of physical state and particle size distribution on dissolution enhancement of nimodipine/PEG solid dispersions prepared by melt mixing and solvent evaporation

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Effect of physical state and particle size distribution on dissolution enhancement of nimodipine/PEG solid dispersions prepared by melt mixing and solvent evaporation

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Effect of physical state and particle size distribution on dissolution enhancement of nimodipine/PEG solid dispersions prepared by melt mixing and solvent evaporation