Basa Shradhanjali, Muniyappan Thilekkumar, Karatgi Pradeep, Prabhu Raghavendra, Pillai Ravi
Department of Pharmacy, Annamalai University, Chidambaram, India.
Drug Dev Ind Pharm. 2008 Nov;34(11):1209-18. doi: 10.1080/03639040802005024.
The objective of this study was to develop a tablet formulation of ketoconazole incorporating drug nanoparticles to enhance saturation solubility and dissolution velocity for enhancing bioavailability and reducing variability in systemic exposure. The bioavailability of ketoconazole is dissolution limited following oral administration. To enhance bioavailability and overcome variability in systemic exposure, a nanoparticle formulation of ketoconazole was developed. Ketoconazole nanoparticles were prepared using a media-milling technique. The nanosuspension was layered onto water-soluble carriers using a fluid bed processor. The nanosuspensions were characterized for particle size before and after layering onto water-soluble carriers. The saturation solubility and dissolution characteristics were investigated and compared with commercial ketoconazole formulation to ascertain the impact of particle size on drug dissolution. The drug nanoparticles were evaluated for solid-state transitions before and after milling using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). This study demonstrated that tablet formulation incorporating ketoconazole nanoparticles showed significantly faster rate of drug dissolution in a discriminating dissolution medium as compared with commercially available tablet formulation. There was no affect on solid-state properties of ketoconazole following milling. The manufacturing process used is relatively simple and scalable indicating general applicability to enhance dissolution and bioavailability of many sparingly soluble compounds.
本研究的目的是开发一种酮康唑片剂制剂，其中包含药物纳米颗粒，以提高饱和溶解度和溶解速度，从而提高生物利用度并降低全身暴露的变异性。酮康唑口服给药后的生物利用度受溶解限制。为提高生物利用度并克服全身暴露的变异性，开发了一种酮康唑纳米颗粒制剂。采用介质研磨技术制备酮康唑纳米颗粒。使用流化床处理器将纳米混悬液分层到水溶性载体上。在将纳米混悬液分层到水溶性载体之前和之后对其粒径进行表征。研究了饱和溶解度和溶解特性，并与市售酮康唑制剂进行比较，以确定粒径对药物溶解的影响。使用差示扫描量热法（DSC）和粉末X射线衍射（PXRD）对研磨前后药物纳米颗粒的固态转变进行评估。本研究表明，与市售片剂制剂相比，含有酮康唑纳米颗粒的片剂制剂在区分性溶解介质中的药物溶解速度明显更快。研磨后酮康唑的固态性质没有受到影响。所使用的制造工艺相对简单且可扩展，表明对提高许多难溶性化合物的溶解和生物利用度具有普遍适用性。
