Pawar Jaywant, Narkhede Rajkiran, Amin Purnima, Tawde Vaishali
BASF India Ltd, Pharma Solutions, Plot No. 12, TTC Area, Thane Belapur Road, Turbhe, Navi Mumbai, 400705, India.
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, University under Section-3 of UGC Act-1956, Elite Status & Centre of Excellence - Govt. of Maharashtra, N. P. Marg, Matunga, Mumbai, 400019, India.
AAPS PharmSciTech. 2017 Aug;18(6):2303-2315. doi: 10.1208/s12249-017-0713-5. Epub 2017 Jan 20.
The aim of the present context was to develop and evaluate a Kolliphor® P407-based transdermal gel formulation of diclofenac sodium by hot melt extrusion (HME) technology; central composite design was used to optimize the formulation process. In this study, we have explored first time ever HME as an industrially feasible and continuous manufacturing technology for the manufacturing of gel formulation using Kolliphor® P407 and Kollisolv® PEG400 as a gel base. Diclofenac sodium was used as a model drug. The HME parameters such as feeding rate, screw speed, and barrel temperature were crucial for the semisolid product development, and were optimized after preliminary trials. For the processing of the gel formulation by HME, a modified screw design was used to obtain a uniform product. The obtained product was evaluated for physicochemical characterization such as differential scanning calorimetry (DSC), X-ray diffraction (XRD), pH measurement, rheology, surface tension, and texture profile analysis. Moreover, it was analyzed for general appearance, spreadibility, surface morphology, and drug content. The optimized gel formulation showed homogeneity and transparent film when applied on a glass slide under microscope, pH was 7.02 and uniform drug content of 100.04 ± 2.74 (SD = 3). The DSC and XRD analysis of the HME gel formulation showed complete melting of crystalline API into an amorphous form. The Kolliphor® P407 and Kollisolv® PEG400 formed excellent gel formulation using HME with consistent viscoelastic properties of the product. An improved drug release was found for the HME gel, which showed a 100% drug release than that of a marketed product which showed only 88% of drug release at the end of 12 h. The Flux value of the HME gel was 106 than that of a marketed formulation, which showed only about 60 value, inferring a significant difference (P < 0.05) at the end of 1 h. This study demonstrates a novel application of the hot melt extrusion process for manufacturing of topical semisolid products.
本文的目的是通过热熔挤出（HME）技术开发并评估一种基于聚氧乙烯蓖麻油衍生物（Kolliphor® P407）的双氯芬酸钠透皮凝胶制剂；采用中心复合设计来优化制剂工艺。在本研究中，我们首次探索将HME作为一种工业上可行的连续制造技术，用于以聚氧乙烯蓖麻油衍生物（Kolliphor® P407）和聚乙二醇400（Kollisolv® PEG400）为凝胶基质制造凝胶制剂。双氯芬酸钠用作模型药物。HME参数如进料速率、螺杆速度和料筒温度对半固体产品的开发至关重要，并在初步试验后进行了优化。为了通过HME加工凝胶制剂，使用了改良的螺杆设计以获得均匀的产品。对所得产品进行了物理化学表征评估，如差示扫描量热法（DSC）、X射线衍射（XRD）、pH测量、流变学、表面张力和质地剖面分析。此外，还对其外观、铺展性、表面形态和药物含量进行了分析。优化后的凝胶制剂在显微镜下涂覆在载玻片上时显示出均匀性和透明薄膜，pH为7.02，药物含量均匀，为100.04±2.74（标准差=3）。HME凝胶制剂的DSC和XRD分析表明，结晶性活性药物成分完全熔化为无定形形式。聚氧乙烯蓖麻油衍生物（Kolliphor® P407）和聚乙二醇400（Kollisolv® PEG400）通过HME形成了具有优异性能的凝胶制剂，产品具有一致的粘弹性。发现HME凝胶的药物释放有所改善，在12小时结束时显示出100%的药物释放，而市售产品仅显示88%的药物释放。HME凝胶的通量值为106，而市售制剂仅显示约60的值，这表明在1小时结束时有显著差异（P<0.05）。本研究证明了热熔挤出工艺在制造局部半固体产品方面的新应用。
