The Drug Delivery and Biomaterials Group, School of Pharmacy, Medical Biology Centre, Queen'sUniversity Belfast, Belfast, Northern Ireland, UK.
J Pharm Pharmacol. 2010 Nov;62(11):1580-90. doi: 10.1111/j.2042-7158.2010.01177.x.
The interest in hot-melt extrusion (HME) as a drug delivery technology for the production of glass solutions is growing rapidly. HME glass solutions have a tendency to recrystallize during storage and also typically have a very dense structure, restricting the ingress of dissolution fluid and retarding drug release. In this study, we have used HME to manufacture glass solutions containing celecoxib (CX) and polyvinylpyrrolidone (PVP) and have assessed the use of supercritical carbon dioxide (scCO2) as a pore-forming agent to enhance drug release. Differential scanning calorimetry confirmed the formation of glass solutions following extrusion. All extrudates exhibited a single glass transition temperature (Tg), positioned between the Tg values of CX and PVP. The instability of glass solutions is a significant problem during storage. Stabilization may be improved through the appropriate choice of excipient to facilitate drug–polymer interactions. The Gordon–Taylor equation showed that the Tg values of all extrudates expected on ideal mixing were lower than those observed experimentally. This may be indicative of drug–polymer interactions that decrease free volume and elevate the Tg. Molecular interactions between CX and PVP were further confirmed using Fourier transform infrared and Raman spectroscopy. Storage stability of the extrudates was shown to be dependent on drug loading. Samples containing a higher CX loading were less stable, which we ascribed to decreased Tg and hence increased mobility within the drug–polymer matrix. The solubility of CX was improved through the formulation of extruded glass solutions, but release rate was relatively slow. Exposure of extrudates to scCO2 had no effect on the solid-state properties of CX but did produce a highly porous structure. The drug-release rate from extrudates after scCO2 exposure was significantly higher.
热熔融挤出（HME）作为一种药物传递技术，用于生产玻璃溶液，其应用兴趣正在迅速增长。HME 玻璃溶液在储存过程中有结晶的趋势，而且通常具有非常致密的结构，限制了溶解液的渗透，从而延缓了药物的释放。在这项研究中，我们使用 HME 制造含有塞来昔布（CX）和聚乙烯吡咯烷酮（PVP）的玻璃溶液，并评估了超临界二氧化碳（scCO2）作为成孔剂来增强药物释放的用途。差示扫描量热法证实挤出后形成了玻璃溶液。所有挤出物都表现出单一的玻璃化转变温度（Tg），位于 CX 和 PVP 的 Tg 值之间。玻璃溶液的不稳定性是储存过程中的一个重大问题。通过选择合适的赋形剂来促进药物-聚合物相互作用，可以改善稳定性。Gordon-Taylor 方程表明，所有挤出物的理论 Tg 值都低于实验观察到的值。这可能表明药物-聚合物相互作用降低了自由体积并提高了 Tg。使用傅里叶变换红外和拉曼光谱进一步证实了 CX 和 PVP 之间的分子相互作用。挤出物的储存稳定性取决于药物负载。含有较高 CX 负载的样品不太稳定，我们将其归因于 Tg 降低，从而导致药物-聚合物基质内的迁移率增加。通过挤出玻璃溶液的配方，提高了 CX 的溶解度，但释放速度相对较慢。暴露于 scCO2 对 CX 的固态性质没有影响，但确实产生了高度多孔的结构。暴露于 scCO2 后挤出物的药物释放速率显著提高。
