依非韦伦通过超声辅助IV-抗溶剂纳米结晶法实现的溶出度增强、物理稳定性及溶出情况

Efavirenz Dissolution Enhancement IV-Antisolvent Nanocrystallization by Sonication, Physical Stability, and Dissolution.

作者信息

Sartori Gabriela Julianelly, Prado Livia Deris, Rocha Helvécio Vinícius Antunes

机构信息

Laboratory of Advanced Pharmaceutical Systems, Farmanguinhos, Fiocruz, Av. Comandante. Guaranys, 447 - Jacarepaguá, Rio de Janeiro, Rio de Janeiro, 22775-903, Brazil.

出版信息

AAPS PharmSciTech. 2017 Nov;18(8):3011-3020. doi: 10.1208/s12249-017-0781-6. Epub 2017 May 10.

Abstract

Efavirenz is a fundamental drug in the HIV therapy; however, it has a low bioavailability due to low water solubility. Particle nanonization should enhance its dissolution and therefore its bioavailability. Nanocrystallization is a promising technique for preparing drug nanocrystals. A solution containing efavirenz (EFV) and methanol was added to an aqueous solution of particle stabilizers, under sonication. The adequate polymer stabilizer and its concentration and drug load were evaluated. Particle size and zeta potential of suspensions were measured. Nanosuspensions were freeze-dried and the resulting powder was characterized by some techniques, with special attention to dissolution. Particle size and zeta potential analysis showed that HMPC and PVP were the most suitable polymers. All samples prepared with these stabilizers had nanosized particles and proper zeta potential; however, sedimentation and particle growth were detected with Turbiscan™. Time-related destabilization occurred when the lowest polymer concentration of 20% was used. SEM analysis of the dried powder shows film formation for suspensions with 40% of polymer and particle aggregation in samples with less polymer. Dissolution profiles of samples were higher than EFV raw material, although the lower the polymer concentration, the higher the dissolution.

摘要

依非韦伦是HIV治疗中的一种基础药物;然而,由于其低水溶性,它的生物利用度较低。药物纳米化应能提高其溶出度,进而提高其生物利用度。纳米结晶是制备药物纳米晶体的一种有前景的技术。在超声处理下,将含有依非韦伦(EFV)和甲醇的溶液加入到颗粒稳定剂的水溶液中。评估了合适的聚合物稳定剂及其浓度和药物载量。测量了悬浮液的粒径和zeta电位。将纳米悬浮液冷冻干燥,并用一些技术对所得粉末进行表征,特别关注溶出度。粒径和zeta电位分析表明,羟丙基甲基纤维素(HMPC)和聚乙烯吡咯烷酮(PVP)是最合适的聚合物。用这些稳定剂制备的所有样品都具有纳米尺寸的颗粒和合适的zeta电位;然而,使用Turbiscan™检测到了沉降和颗粒生长。当使用最低聚合物浓度20%时,发生了与时间相关的不稳定现象。对干燥粉末的扫描电子显微镜(SEM)分析表明,聚合物含量为40%的悬浮液形成了薄膜,聚合物含量较低的样品中存在颗粒聚集。样品的溶出曲线高于依非韦伦原料药,尽管聚合物浓度越低,溶出度越高。

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