Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Campus Trindade, 88040-970, Florianópolis, SC, Brazil.
Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Campus Trindade, 88040-970, Florianópolis, SC, Brazil; Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, 06269-3092, Storrs, CT, USA.
Carbohydr Polym. 2019 Apr 1;209:207-214. doi: 10.1016/j.carbpol.2019.01.007. Epub 2019 Jan 3.
Solid dispersions (SDs) of chlorthalidone (CTD) are promising systems to enhance drug dissolution rate, generate and maintain drug supersaturation levels in gastrointestinal fluids. In this work, SDs of CTD were prepared by spray drying using sodium alginate (SA) as carrier. Six formulations were prepared, varying the drug loading and composition, through the combination of SA with surfactants (sodium lauryl sulfate (SLS) or polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOL)). In all SDs, except when SA was used alone at low drug loading, CTD was in the amorphous form. At sink conditions, all SDs showed a faster dissolution rate than the crystalline drug. At non-sink conditions, the SDs prepared with SA and SLS at low drug loading exhibited the best performance to maintain supersaturating drug levels. All SDs, except those prepared with SA alone or SA-SLS at high drug loading, presented no drug recrystallization after 34 months of storage.
固体分散体（SDs）是一种有前途的系统，可以提高药物的溶解速率，在胃肠道液体中产生和维持药物过饱和水平。在这项工作中，使用海藻酸钠（SA）作为载体，通过喷雾干燥法制备了氯噻酮（CTD）的 SDs。通过将 SA 与表面活性剂（月桂基硫酸钠（SLS）或聚己内酯-醋酸乙烯酯-聚乙二醇接枝共聚物（SOL））组合，制备了 6 种制剂，改变了药物载药量和组成。除了在低药物载药量下单独使用 SA 时，所有 SDs 中的 CTD 均为无定形形式。在溶出条件下，所有 SDs 的溶解速率均快于晶型药物。在非溶出条件下，低药物载药量下用 SA 和 SLS 制备的 SDs 表现出维持过饱和药物水平的最佳性能。除了在高药物载药量下单独使用 SA 或 SA-SLS 制备的 SDs 外，所有 SDs 在储存 34 个月后均未出现药物再结晶。
