Drug–excipient complexation in lipid based delivery systems: An investigation of the Tipranavir-1,3-dioctanolyglycerol complex
✍ Scribed by Shirlynn Chen; Mayur S. Dudhedia; Zeren Wang; Richard T. Darrington; Toby Tamblyn; John A. Smoliga; Paul-James Jones; Steven L. Krill
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 322 KB
- Volume
- 98
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
This report describes the solubility properties of a poorly soluble drugexcipient complex in a lipid based formulation. Tipranavir (TPV) was used as the model drug and 1,3-dioctanoylglycerol (DOG) as the excipient. The TPV-DOG complex was prepared by dissolving TPV and DOG in ethanol at 608C followed by evaporation of ethanol. The formation of the complex with a 4:1 TPV-to-DOG molar ratio was confirmed by XRPD, DSC, and NMR. At 258C, total solubility of TPV decreased with increasing DOG concentration. The solubility properties of the TPV-DOG complex can be described by two simultaneous equilibria: a liquid-solid phase equilibrium of the complex and a species equilibrium among the various species in the liquid phase. A model equation was derived accordingly with two parameters, the intrinsic solubility of the complex (S o ), and the solution complex constant (K 41 ). The model was in good agreement with experimental results. The values of S o and K 41 are 0.0186 AE 0.0025 (M) and 21.97 AE 7.19 (1/M 4 ), respectively. The equation can successfully predict the concentrations of total and free TPV as a function of DOG in the formulation. The approach developed provides a useful tool for rationale selection of excipients and their levels to avoid drug precipitation in lipid based formulations.