Moin Afrasim, Roohi N K Famna, Rizvi Syed Mohd Danish, Ashraf Syed Amir, Siddiqui Arif Jamal, Patel Mitesh, Ahmed S M, Gowda D V, Adnan Mohd
Department of Pharmaceutics, College of Pharmacy, University of Hail PO Box 2440 Hail Saudi Arabia.
Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research S S Nagar Mysuru 570015 Karnataka India
RSC Adv. 2020 Sep 21;10(57):34869-34884. doi: 10.1039/d0ra06611g. eCollection 2020 Sep 16.
Three drugs namely caffeine, paracetamol, and aceclofenac are commonly used for treating various acute and chronic pain related ailments. These 3 drugs have varied solubility profiles, and formulating them into a single tablet did not have the desired dissolution profile for drug absorption. The objective of the present research was to tailor the drug release profile by altering drug solubility. This was achieved by loading the drug into nanosponges. Here, three-dimensional colloidal nanosponges were prepared using β-cyclodextrin with dimethyl carbonate as a cross-linker using the hot-melt compression method. The prepared nanosponges were characterized by FTIR, H NMR spectroscopy, DSC, XRPD studies and SEM. The FTIR and DSC results obtained indicated polymer-drug compatibility. The H NMR spectroscopy results obtained indicated the drug entrapment within nanosponges with the formation of the inclusion complex. XRPD studies showed that the loaded drug had changed crystalline properties altering drug solubility. SEM photographs revealed the porous and spongy texture on the surface of the nanosponge. Box-Behnken experimental design was adopted for the optimization of nanosponge synthesis. Among the synthesized nanosponges containing paracetamol, aceclofenac and caffeine, batch F3-P31, F3-A31 and F3-C31 were considered optimized. Their particle size was 185, 181 and 199 nm with an entrapment efficiency of 81.53, 84.96, and 89.28% respectively. These optimized nanosponges were directly compressed into tablets and were studied for both pre and post-compression properties including drug release. The prepared tablet showed desired drug dissolution properties compared to the pure drug. The above outcomes indicated the applicability of nanosponges in modulating the drug release with varied solubility for combination therapy.
咖啡因、对乙酰氨基酚和醋氯芬酸这三种药物通常用于治疗各种急慢性疼痛相关疾病。这三种药物具有不同的溶解度特征，将它们制成单一片剂时，其溶出特征并不符合药物吸收的理想情况。本研究的目的是通过改变药物溶解度来调整药物释放特征。这是通过将药物载入纳米海绵来实现的。在此，使用β-环糊精与碳酸二甲酯作为交联剂，采用热熔压缩法制备了三维胶体纳米海绵。通过傅里叶变换红外光谱（FTIR）、核磁共振氢谱（H NMR）、差示扫描量热法（DSC）、X射线粉末衍射（XRPD）研究和扫描电子显微镜（SEM）对制备的纳米海绵进行了表征。获得的FTIR和DSC结果表明聚合物与药物具有相容性。获得的H NMR光谱结果表明药物被包封在纳米海绵中并形成了包合物。XRPD研究表明，载入的药物改变了晶体性质，从而改变了药物溶解度。SEM照片显示了纳米海绵表面的多孔和海绵状质地。采用Box-Behnken实验设计对纳米海绵的合成进行优化。在含有对乙酰氨基酚、醋氯芬酸和咖啡因的合成纳米海绵中，批次F3-P31、F3-A31和F3-C31被认为是优化的。它们的粒径分别为185、181和199 nm，包封率分别为81.53%、84.96%和89.28%。将这些优化后的纳米海绵直接压制成片剂，并对其压片前后的性质（包括药物释放）进行了研究。与纯药物相比，制备的片剂显示出理想的药物溶出性质。上述结果表明纳米海绵在调节具有不同溶解度的药物释放以进行联合治疗方面具有适用性。
