The present study was aimed to enhance the solubility and dissolution of BCS class II drug, telmisartan (TEM), by nanoformulation approach. Several attempts were made to develop a nanosuspension by bottom-up and top-down techniques. In our study, we found in situ nanoamorphization technique to be incompatible and hence was not selected for further development of nanoformulation. Bottom-up techniques such as anti-solvent precipitation and emulsification solvent evaporation methods failed to reduce the size of the drug to nanoform by HPMC E15 and PVP K-25 at 1500–2000 rpm but resulted in micron-sized particles. However, the acid-base neutralization method has produced nanosuspension with a particle size of 243.9 nm and 0.119 PDI. Formulation and analytical development were carried out by statistical factorial design using the Design-Expert software (version 11.0). The nanosuspensions remained stable even after 90 days without any aggregations with particle size 338.1 nm and PDI 0.146. Zeta potential of optimized formulation was found to be − 16.2 mV. Drug content and its release were estimated by the developed and validated in-house HPLC method. In vitro drug diffusion studies on the optimized formulation have shown a drug release of 82.6% by the end of 3 h, whereas plain drug suspension has shown only 42.8% release, indicating a 2-fold increase of drug diffusion with nanosuspension. Ex vivo drug permeation studies performed using excised goat gastric mucosa revealed much faster permeation of TEM from nanosuspension than the plain drug suspension. Hence, from the results, it can be concluded that TEM, when formulated by acid-base neutralization method as a nanosuspension, leads to enhanced solubility, dissolution, and stability.

中文翻译：

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基于实验设计（DoE）的方法开发和优化替米沙坦（BCS II类降压药物）的纳米悬浮液

本研究旨在通过纳米配方方法提高BCS II类药物替米沙坦（TEM）的溶解度和溶解度。为了通过自下而上和自上而下的技术开发纳米悬浮液，进行了多种尝试。在我们的研究中，我们发现原位纳米非晶化技术不兼容，因此未被选择用于进一步发展纳米配方。自下而上的技术（例如抗溶剂沉淀法和乳化溶剂蒸发法）未能通过HPMC E15和PVP K-25在1500-2000 rpm的速度下将药物尺寸减小为纳米形式，但产生了微米级的颗粒。但是，酸碱中和法制得的纳米悬浮液的粒径为243.9 nm，PDI为0.119。使用Design-Expert软件（版本11.0）通过统计析因设计进行配方和分析开发。纳米悬浮液即使在90天后仍保持稳定，没有任何聚集，粒径为338.1 nm，PDI为0.146。发现优化配方的ζ电势为-16.2 mV。通过开发和验证的内部HPLC方法估算药物含量及其释放。对优化配方进行的体外药物扩散研究显示，到3 h结束时，药物释放率为82.6％，而普通药物悬浮液的释放仅为42.8％，这表明纳米悬浮液使药物扩散增加了2倍。使用切除的山羊胃粘膜进行的离体药物渗透研究表明，纳米悬浮液对TEM的渗透要比普通药物悬浮液快得多。因此，从结果来看，