University of Sunderland, Faculty of Applied Sciences, Department of Pharmacy,Health and Well-being, Sunderland, SR1 3SD, UK.
Pharm Dev Technol. 2013 Nov-Dec;18(6):1379-90. doi: 10.3109/10837450.2012.723718. Epub 2012 Sep 20.
Hydrophobic drugs present a challenge due to: (i) adhesion and agglomeration; hence the choice of the suitable processing technique to have the drugs into orally administered dosage forms is critical. (ii) Poor dissolution and poor aqueous solubility; hence poor bioavailability. A novel method which is in situ lyophilisation directly in hard gelatin capsule shells was used in this research to enhance the dissolution of nifedipine (a model hydrophobic drug) in the presence of co-povidone, Pluronic(®)F-127 and inulin as enhancement excipients (to the best of our knowledge those excipients have not been previously used with nifedipine in lyophilised forms). Solutions of nifedipine and excipients in a range of concentrations (0.5, 1, 5 and 10%w/v) were prepared using a co-solvent system of tert- butyl alcohol/water mixture. These solutions were filled directly into bodies of size 000 hard gelatin capsule shells and freeze dried. Pure drug and all formulations were characterised by solubility, wetting studies and in vitro dissolution. Also, conformational integrity and thermal characteristics of nifedipine formulations were investigated using FT-IR spectroscopy and differential scanning calorimetry (DSC), respectively. The in situ lyophilisation of nifedipine with excipients, looks a promising method not only to improve the hydrophobic drug dissolution but also to be cost effective.
(i) 粘附和团聚；因此，选择合适的加工技术将药物制成口服剂型至关重要。(ii) 溶解和水溶性差；因此生物利用度差。本研究采用原位冷冻干燥法直接在硬明胶胶囊壳中进行，以提高硝苯地平（模型疏水性药物）在共聚维酮、泊洛沙姆®F-127 和菊粉作为增强赋形剂存在时的溶解度（据我们所知，这些赋形剂以前没有在冻干形式下与硝苯地平一起使用过）。使用叔丁醇/水混合共溶剂系统制备了一系列浓度（0.5、1、5 和 10%w/v）的硝苯地平和赋形剂溶液。将这些溶液直接填充到 000 号硬明胶胶囊体中并冷冻干燥。通过溶解度、润湿研究和体外溶解研究对纯药物和所有制剂进行了表征。此外，还分别使用傅里叶变换红外光谱法（FT-IR 光谱法）和差示扫描量热法（DSC）研究了硝苯地平制剂的构象完整性和热特性。用赋形剂进行原位冷冻干燥，不仅有望提高疏水性药物的溶解度，而且具有成本效益。
