用于肺结核治疗中吸入高剂量给药的利福平多晶型的研究。,International Journal of Pharmaceutics

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用于肺结核治疗中吸入高剂量给药的利福平多晶型的研究。
International Journal of Pharmaceutics ( IF 5.3 ) Pub Date : 2020-07-11 , DOI: 10.1016/j.ijpharm.2020.119602
Prakash Khadka ₁ , Philip C Hill ₂ , Boya Zhang ₁ , Rajesh Katare ₃ , Jack Dummer ₄ , Shyamal C Das ₁

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利福平是目前口服使用的一线高效药物，作为抗结核 (TB) 长期多药治疗方案的一部分。尽管吸入疗法具有作为治疗结核病的有效方法的潜力，但尚未开发出可用于临床应用的利福平吸入制剂。为此，有必要评估其固态特性，这些特性调节了溶解度、溶解度、雾化、稳定性和生物利用度等重要特性。在这项研究中，结晶技术和喷雾干燥用于制备可吸入利福平制剂。喷雾干燥产生利福平的无定形制剂，而结晶二水合物和五水合物制剂通过结晶获得。评估粉末的固态特性，在不同相对湿度条件下储存三个月的体外气雾化和气雾化稳定性。所有配方的平均粒径均小于 3.8 µm，细颗粒分数 (FPF) 高于 58.0%。无定形和结晶二水合物制剂在储存三个月后显示出雾化参数（发射剂量和 FPF）没有变化。发现无定形和五水合物制剂在储存时会发生氧化降解，并且观察到它们的药物含量减少。在制备的制剂中，利福平二水合物制剂在三个月内降解最少。本研究中制备的可吸入利福平制剂不含赋形剂，

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A study on polymorphic forms of rifampicin for inhaled high dose delivery in tuberculosis treatment.

Rifampicin is a first-line, highly effective drug currently used orally as a part of a lengthy multi-drug regimen against tuberculosis (TB). Despite the potential of inhaled therapy as an effective approach for TB treatment, an inhalable formulation of rifampicin has not yet been developed for clinical use. In order to do so, it is necessary to evaluate its solid-state properties, which regulate important characteristics like solubility, dissolution, aerosolization, stability and bioavailability. In this study, a crystallization technique and spray drying were used to prepare inhalable rifampicin formulations. Spray drying yielded amorphous formulation of rifampicin while crystalline dihydrate and pentahydrate formulations were obtained by crystallization. The powders were evaluated for their solid-state properties, in vitro aerosolization and aerosolization stability for three months when stored at different relative humidity conditions. All formulations had a mean particle size smaller than 3.8 µm and had a fine particle fraction (FPF) higher than 58.0%. Amorphous and crystalline dihydrate formulations showed no change in aerosolization parameters (emitted dose and FPF) upon storage for three months. The amorphous and pentahydrate formulations were found to undergo oxidative degradation upon storage, and a decrease in their drug content was observed. Among the formulations prepared, rifampicin dihydrate formulation showed the least degradation over the three months period. The inhalable rifampicin formulations prepared in this study, being excipient free, have the potential to be delivered as inhaled dry powder high-dose rifampicin to the lungs for effective treatment of TB.

更新日期：2020-07-11

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