Stochiometrically governed molecular interactions in drug: Poloxamer solid dispersions
Stochiometrically governed molecular interactions in drug: Poloxamer solid dispersions
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DOI：
10.1016/j.ijpharm.2010.03.014
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发表时间：
2010-05-31
影响因子：
5.8
通讯作者：
Rawlinson, C. F.
中科院分区：
文献类型：
--
作者：
Ali, W.;Williams, A. C.;Rawlinson, C. F.
本研究探讨了模型药物和波洛沙莫之间的分子相互作用，这些相互作用促进了固体分散体溶解速度的提高。以不同摩尔比的poloxamers 407和188制备了布洛芬和酮洛芬固体分散体。在药物与载体摩尔比为2:1的固体分散体红外光谱中，布洛芬二聚体的羰基拉伸振动向更高的波数移动，表明布洛芬二聚体在药物与载体之间形成氢键的同时被破坏。药物与载体的摩尔比为>2:1的固体分散体（高达29:1）表明布洛芬与波洛沙姆氢键结合，过量的药物以二聚体的形式存在。x射线衍射研究证实了这些发现，没有证据表明在2:1摩尔比系统中存在结晶性药物，而较高的药物负荷保留了结晶性布洛芬。酮洛芬-波洛沙姆固体分散体也发现了类似的结果。布洛芬-波洛沙姆407固体分散体的热分析及其相图表明，根据载药量不同，形成了固溶体和共晶体系。溶解度研究表明，从固溶体中释放最快；固溶体的溶出率比布洛芬粉末的溶出率高12倍，而共晶体系的溶出率比布洛芬粉末高6倍。当设计固体分散体以改善难水溶性药物的递送时，药物与载体相互作用的性质（由组成物的化学计量控制）会影响溶解速率的提高。(C) 2010 Elsevier B.V.版权所有
This study probes the molecular interactions between model drugs and poloxamers that facilitate dissolution rate improvements using solid dispersions. Ibuprofen and ketoprofen solid dispersions were prepared at different mole ratios using poloxamers 407 and 188. The carbonyl stretching vibration of the ibuprofen dimer shifted to higher wavenumber in the infrared spectra of 2:1 drug:carrier mole ratio solid dispersions, indicating disruption of the ibuprofen dimer concomitant with hydrogen bond formation between the drug and carrier. Solid dispersions with mole ratios >2:1 drug:carrier (up to 29:1) showed both ibuprofen hydrogen-bonded to the poloxamer, and excess drug present as dimers. X-ray diffraction studies confirmed these findings with no evidence of crystalline drug in 2:1 mole ratio systems whereas higher drug loadings retained crystalline ibuprofen. Similar results were found with ketoprofen-poloxamer solid dispersions. Thermal analysis of ibuprofen-poloxamer 407 solid dispersions and their resultant phase diagram suggested solid solutions and a eutectic system were formed, depending on drug loading. Dissolution studies showed fastest release from the solid solutions; dissolution rates from solid solutions were 12-fold greater than the dissolution of ibuprofen powder whereas the eutectic system gave a 6-fold improvement over the powder. When designing solid dispersions to improve the delivery of poorly-water soluble drugs, the nature of drug:carrier interactions, which are governed by the stochiometry of the composition, can affect the dissolution rate improvement. (C) 2010 Elsevier B.V. All rights reserved.