Co-amorphous simvastatin and glipizide combinations show improved physical stability without evidence of intermolecular interactions

Korbinian Löbmann, Clare Strachan, Holger Grohganz, Thomas Rades, Ossi Korhonen, Riikka Laitinen

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    Abstract

    The objective of this study was to prepare a co-amorphous drug/drug combination between two BCS class II drugs, simvastatin (SVS) and glipizide (GPZ). This pharmacologically relevant combination of two drugs could produce a promising candidate for formulations intended for combination therapy of metabolic disorders. The co-amorphous SVS-GPZ mixtures (molar ratios 2:1, 1:1 and 1:2) were prepared by mechanical activation (ball milling or cryomilling) and characterized with respect to their thermal properties, possible molecular interactions, dissolution properties and physical stability, and compared to the behaviour of pure amorphous forms and their physical mixtures. It was found that even though a molecular mixture was achieved with all SVS-GPZ mixture ratios, no molecular interactions between the drugs could be detected. By formation of co-amorphous single-phase mixtures, only the dissolution rate of GPZ could be improved. The co-amorphous mixtures showed improved stability compared to the pure amorphous forms and the amorphous physical mixtures. It was concluded that this was attributable to the molecular level mixing of SVS with GPZ upon milling, and GPZ is acting as an anti-plasticizer in these mixtures.
    Original languageEnglish
    JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
    Volume81
    Issue number1
    Pages (from-to)159-69
    Number of pages11
    ISSN0939-6411
    DOIs
    Publication statusPublished - 2012

    Keywords

    • Drug Combinations
    • Drug Compounding
    • Drug Incompatibility
    • Drug Stability
    • Glipizide
    • Hypoglycemic Agents
    • Hypolipidemic Agents
    • Simvastatin
    • Solubility

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