School of Pharmaceutical Sciences and Technology, Sardar Bhagwan Singh University, Balawala, Dehradun, Uttarakhand 248001,India.
Comb Chem High Throughput Screen. 2022;25(2):307-323. doi: 10.2174/1386207323666201218115149.
Solubility/dissolution is said to be the key factor that influences the oral bioavailability of drug and is also the rate limiting step in formulation development.
Hydrochlorothiazide (HCZ) is a BCS Class IV drug with low solubility and low permeability. The present work aimed to increase the solubility of hydrochlorothiazide using blends of natural and synthetic hydrotropes.
Two hydrotropes one from natural (piperazine) and other from the synthetic origin (sodium benzoate) were selected for the formulation of solid dispersion (SD) of HCZ. Preliminary trial batches were prepared by considering the safe dose of both the selected hydrotropes i.e. sodium benzoate (SB) and piperazine (PP). A 32 full factorial design was opted for preparing the optimized solid dispersion of hydrochlorothiazide.
The quadratic models were found to be best fitted for the studied responses, which were percent solubility and in-vitro drug release. The results showed increased solubility and in-vitro drug release of HCZ solid dispersions as a function of increasing levels of both hydrotropes.
In this work, it was concluded that the use of natural hydrotropes along with synthetic hydrotropes gave an effective and safe approach for the solubility enhancement of the HCZ.
溶解度/溶解被认为是影响药物口服生物利用度的关键因素，也是制剂开发的限速步骤。
氢氯噻嗪（HCZ）是一种 BCS 分类为 IV 类的药物，其溶解度和渗透性都较低。本工作旨在使用天然和合成增溶剂的混合物来提高氢氯噻嗪的溶解度。
选择两种增溶剂，一种来自天然（哌嗪），另一种来自合成（苯甲酸钠），用于氢氯噻嗪的固体分散体（SD）的制剂。初步试验批次的制备考虑了两种选定的增溶剂（苯甲酸钠（SB）和哌嗪（PP））的安全剂量。选择 32 个完全因子设计来制备优化的氢氯噻嗪固体分散体。
发现二次模型最适合研究的响应，即溶解度和体外药物释放。结果表明，随着两种增溶剂水平的增加，氢氯噻嗪固体分散体的溶解度和体外药物释放均得到提高。
在这项工作中，我们得出结论，使用天然增溶剂和合成增溶剂是提高 HCZ 溶解度的有效且安全的方法。
