Amorphous solid dispersions (ASDs) are of great interest due to their ability to enhance the delivery of poorly soluble drugs. Recent studies have shown that, in addition to acting as a crystallization inhibitor, the polymer in an ASD plays a role in controlling the rate of drug release, notably in congruently releasing formulations, where both the drug and polymer have similar normalized release rates. The aim of this study was to compare the solid-state stability and release performance of ASDs when formulated with neutral and enteric polymers. One neutral (polyvinylpyrrolidone–vinyl acetate copolymer, PVPVA) and four enteric polymers (hypromellose acetate succinate; hypromellose phthalate; cellulose acetate phthalate, CAP; methacrylic acid–methyl methacrylate copolymer, Eudragit L 100) were used to formulate binary ASDs with lumefantrine, a hydrophobic and weakly basic antimalarial drug. The normalized drug and polymer release rates of lumefantrine–PVPVA ASDs up to 35% drug loading (DL) were similar and rapid. No drug release from PVPVA systems was detected when the DL was increased to 40%. In contrast, ASDs formulated with enteric polymers showed a DL-dependent decrease in the release rates of both the drug and polymer, whereby release was slower than for PVPVA ASDs for DLs < 40% DL. Drug release from CAP and Eudragit L 100 systems was the slowest and drug amorphous solubility was not achieved even at 5% DL. Although lumefantrine–PVPVA ASDs showed fast release, they also showed rapid drug crystallization under accelerated stability conditions, while the ASDs with enteric polymers showed much greater resistance to crystallization. This study highlights the importance of polymer selection in the formulation of ASDs, where a balance between physical stability and dissolution release must be achieved.

中文翻译：

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平衡 Lumefantrine 无定形固体分散体的固态稳定性和溶解性能：聚合物选择和药物-聚合物相互作用的作用

无定形固体分散体 (ASD) 因其增强难溶性药物递送的能力而备受关注。最近的研究表明，除了作为结晶抑制剂外，ASD 中的聚合物在控制药物释放速率方面也发挥作用，特别是在一致释放的制剂中，其中药物和聚合物具有相似的标准化释放速率。本研究的目的是比较使用中性和肠溶性聚合物配制的 ASD 的固态稳定性和释放性能。使用一种中性（聚乙烯吡咯烷酮-醋酸乙烯酯共聚物，PVVPA）和四种肠溶聚合物（醋酸羟丙甲纤维素琥珀酸酯；邻苯二甲酸羟丙甲纤维素；醋酸邻苯二甲酸纤维素，CAP；甲基丙烯酸-甲基丙烯酸甲酯共​​聚物，Eudragit L 100）与苯芴醇一起配制二元 ASD，一种疏水性弱碱性抗疟药。在高达 35% 载药量 (DL) 的苯芴醇-PVPVA ASD 的归一化药物和聚合物释放率相似且快速。当 DL 增加到 40% 时，未检测到 PVVPA 系统的药物释放。相比之下，用肠溶聚合物配制的 ASD 显示出药物和聚合物的释放速率依赖于 DL，因此对于 DL < 40% DL 的释放比 PVVPA ASD 慢。CAP 和 Eudragit L 100 系统的药物释放最慢，即使在 5% DL 下也没有达到药物无定形溶解度。尽管苯芴醇-PVPVA ASD 表现出快速释放，但它们在加速稳定性条件下也表现出快速的药物结晶，而含有肠溶聚合物的 ASD 表现出更大的抗结晶性。