Otto H York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
Int J Pharm. 2011 Jul 29;414(1-2):321-31. doi: 10.1016/j.ijpharm.2011.05.028. Epub 2011 May 12.
This study establishes and compares structure-property-processing relationships on three drug delivery systems containing an anionic active pharmaceutical ingredient (API) in the following excipient carriers: (a) an inorganic anionic nanoclay, (b) pH responsive acrylic polymers, and (c) combinations thereof. The effects of the excipients on the APIs dissolution rate were studied from their release profile in simulated body fluids (SBFs) with different pH. In the API-nanoclay system, calcination of the clay followed by its reconstitution in an API solution was successfully used to intercalate the API in its amorphous state in the clay. As a result, the API showed increased apparent solubility vs. its crystalline form with its release mechanism from the clay being predominantly diffusion controlled and depending on the pH of the SBFs. In melt mixed ternary polymer systems containing the above hybrids, as a result of an additional diffusional step due to presence of nanoplatelets, the API showed a more controlled release vs. polymer systems that contained only API. By comparison to the low pH SBF, the ternary system in the pH 7.4 SBF showed a reduced diffusion contribution due to the presence of clay platelets, the latter unaffected by the high pH value. Reasonable agreement was found with predictions from literature diffusion/erosion models. It is confirmed that hot melt mixing offers opportunities to produce systems with enhanced API apparent solubility. The presence of nanoclays can also increase the API's apparent solubility and affect its release in a controlled manner.
本研究建立并比较了三种载药体系的结构-性质-加工关系，这三种载药体系均含有一种阴离子活性药物成分（API），其赋形剂载体分别为：（a）无机阴离子纳米黏土，（b）pH 响应性丙烯酸聚合物，以及（c）二者的组合。通过在不同 pH 值的模拟体液（SBF）中释放曲线，研究了赋形剂对 API 溶出速率的影响。在 API-纳米黏土体系中，通过对黏土进行煅烧并将其重新配置在 API 溶液中，可以成功地将 API 以无定形状态嵌入到黏土中。结果表明，与 API 的结晶形式相比，API 的表观溶解度有所增加，其释放机制主要为扩散控制，且取决于 SBF 的 pH 值。在含有上述混合物的熔融共混三元聚合物体系中，由于纳米片的存在增加了一个额外的扩散步骤，API 的释放比仅含有 API 的聚合物体系更为可控。与低 pH 值的 SBF 相比，在 pH 值为 7.4 的 SBF 中，三元体系的扩散贡献由于黏土片的存在而降低，后者不受高 pH 值的影响。与文献中的扩散/侵蚀模型的预测结果具有良好的一致性。结果证实，热熔混合为提高 API 表观溶解度提供了机会。纳米黏土的存在还可以以可控的方式增加 API 的表观溶解度并影响其释放。
