Co-amorphous simvastatin and glipizide combinations show improved physical stability without evidence of intermolecular interactions
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Co-amorphous simvastatin and glipizide combinations show improved physical stability without evidence of intermolecular interactions. / Löbmann, Korbinian; Strachan, Clare; Grohganz, Holger; Rades, Thomas; Korhonen, Ossi; Laitinen, Riikka.
In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 81, No. 1, 2012, p. 159-69.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Co-amorphous simvastatin and glipizide combinations show improved physical stability without evidence of intermolecular interactions
AU - Löbmann, Korbinian
AU - Strachan, Clare
AU - Grohganz, Holger
AU - Rades, Thomas
AU - Korhonen, Ossi
AU - Laitinen, Riikka
N1 - Copyright © 2012 Elsevier B.V. All rights reserved.
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Drug Combinations
KW - Drug Compounding
KW - Drug Incompatibility
KW - Drug Stability
KW - Glipizide
KW - Hypoglycemic Agents
KW - Hypolipidemic Agents
KW - Simvastatin
KW - Solubility
U2 - 10.1016/j.ejpb.2012.02.004
DO - 10.1016/j.ejpb.2012.02.004
M3 - Journal article
C2 - 22353489
VL - 81
SP - 159
EP - 169
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
SN - 0939-6411
IS - 1
ER -
ID: 43944734