Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taibah University, Almadinah, Almunawarah, Kingdom of Saudi Arabia.
King's College London, Institute of Pharmaceutical Science, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
Sci Rep. 2017 Jun 6;7(1):2910. doi: 10.1038/s41598-017-02676-2.
Conversion into the amorphous form enhances the dissolution of poorly soluble drugs, however the barrier to market for medicines containing an amorphous drug is poor stability. The aim was to produce the amorphous form of a drug within a capsule, without thermal or mechanical stress during manufacture. To facilitate this aim, the mechanism for drug-polymer interaction was explored. Nifedipine and polyvinylpyrrolidone were dissolved in tert-butanol at different drug/polymer ratios. These solutions were dispensed into gelatin capsules and freeze-dried. Differential scanning calorimetry (DSC) & novel FT-IR analysis based on peak symmetry measurements confirmed the absence of crystallinity when polyvinylpyrrolidone exceeded 50%w/w. Capsules containing 10 mg of nifedipine were amorphous and stable for over 3 months at ≈40 °C. Evidence of hydrogen bonding between the N-H group of nifedipine and the C=O group of PVP was observed and this interaction inhibited nifedipine crystallisation. PVP's high affinity for water and the nifedipine-polymer interaction lead to a significant dissolution rate enhancement. The freeze-dried capsule, 10%w/w nifedipine/PVP, had the highest dissolution rate constant of 0.37 ± 0.05 min, and the lowest time to achieve 50% dissolution or t of 1.88 ± 0.05 min. This formulation reached 80% dissolved in less than 6 min whereas the equivalent marketed liquid filled nifedipine capsule took 3 times longer to reach 80% dissolution.
将药物转化为无定形形式可以提高难溶性药物的溶解度，但含有无定形药物的药物进入市场的障碍是其稳定性差。本研究的目的是在不产生热或机械应力的情况下，在胶囊内制备药物的无定形形式。为了实现这一目标，探索了药物-聚合物相互作用的机制。硝苯地平和聚乙烯吡咯烷酮分别以不同的药物/聚合物比例溶解在叔丁醇中。将这些溶液分配到明胶胶囊中并冷冻干燥。差示扫描量热法（DSC）和基于峰对称性测量的新型傅里叶变换红外（FT-IR）分析证实，当聚乙烯吡咯烷酮超过 50%w/w 时，无定形。含有 10mg 硝苯地平的胶囊是无定形的，在 ≈40°C 下稳定超过 3 个月。观察到硝苯地平的 N-H 基团和 PVP 的 C=O 基团之间存在氢键相互作用，这种相互作用抑制了硝苯地平的结晶。PVP 对水的高亲和力和硝苯地平-聚合物相互作用导致显著的溶解速率增强。冻干胶囊中，硝苯地平/聚乙烯吡咯烷酮 10%w/w 的药物释放速率常数最高，为 0.37±0.05min，达到 50%溶解所需的时间 t 最短，为 1.88±0.05min。该配方在不到 6 分钟内达到 80%的溶解，而等效的市售硝苯地平填充液体胶囊则需要 3 倍的时间才能达到 80%的溶解。
