Panzade Prabhakar, Shendarkar Giridhar, Shaikh Sarfaraj, Balmukund Rathi Pavan
Department of Pharmacognosy, Nanded Pharmacy College, Opp. Kasturba Matruseva Kendra, Shyam Nagar, Nanded, India.
Department of Pharmaceutics, Shri Bhagwan College of Pharmacy, Dr. Y. S. khedkar Marg, CIDCO, Aurangabad, India.
Adv Pharm Bull. 2017 Sep;7(3):399-408. doi: 10.15171/apb.2017.048. Epub 2017 Sep 25.
Cocrystallisation of drug with coformers is a promising approach to alter the solid sate properties of drug substances like solubility and dissolution. The objective of the present work was to prepare, formulate and evaluate the piroxicam cocrystal by screening various coformers. Cocrystals of piroxicam were prepared by dry grinding method. The melting point and solubility of crystalline phase was determined. The potential cocrystal was characterized by DSC, IR, XRPD. Other pharmaceutical properties like solubility and dissolution rate were also evaluated. Orodispersible tablets of piroxicam cocrystal were formulated, optimized and evaluated using 3 factorial design. Cocrystals of piroxicam-sodium acetate revealed the variation in melting points and solubility. The cocrystals were obtained in 1:1 ratio with sodium acetate. The analysis of Infrared explicitly indicated the shifting of characteristic bands of piroxicam. The X-Ray Powder Diffraction pattern denoted the crystallinity of cocrystals and noteworthy difference in 2θ value of intense peaks. Differential scanning calorimetry spectra of cocrystals indicated altered endotherms corresponding to melting point. The pH solubility profile of piroxicam showed sigmoidal curve, which authenticated the pKa-dependent solubility. Piroxicam cocrystals also exhibited a similar pH-solubility profile. The cocrystals exhibited faster dissolution rate owing to cocrystallization as evident from 30% increase in the extent of dissolution. The orodispersible tablets of piroxicam cocrystals were successfully prepared by direct compression method using crosscarmelose sodium as superdisintegrant with improved disintegration time (30 sec) and dissolution rate. The piroxicam cocrystal with modified properties was prepared with sodium acetate and formulated as orodispersible tablets having faster disintegration and greater dissolution rate.
药物与共形成物的共结晶是一种改变药物固态性质(如溶解度和溶出度)的有前景的方法。本研究的目的是通过筛选各种共形成物来制备、配制和评估吡罗昔康共晶体。采用干磨法制备吡罗昔康共晶体。测定了结晶相的熔点和溶解度。通过差示扫描量热法(DSC)、红外光谱(IR)、X射线粉末衍射(XRPD)对潜在的共晶体进行了表征。还评估了其他药学性质,如溶解度和溶出速率。采用三因素设计对吡罗昔康共晶体的口腔崩解片进行了配制、优化和评估。吡罗昔康 - 醋酸钠共晶体显示出熔点和溶解度的变化。共晶体与醋酸钠以1:1的比例获得。红外分析明确表明了吡罗昔康特征峰的位移。X射线粉末衍射图谱表明了共晶体的结晶度以及强峰2θ值的显著差异。共晶体的差示扫描量热光谱表明对应熔点的吸热峰发生了改变。吡罗昔康的pH溶解度曲线呈S形,证实了其依赖于pKa的溶解度。吡罗昔康共晶体也表现出类似的pH - 溶解度曲线。由于共结晶,共晶体表现出更快的溶出速率,溶出度提高了30%,这一点很明显。以交联羧甲基纤维素钠为超级崩解剂,采用直接压片法成功制备了吡罗昔康共晶体的口腔崩解片,其崩解时间缩短(30秒),溶出速率提高。用醋酸钠制备了具有改良性质的吡罗昔康共晶体,并将其制成口腔崩解片,具有更快的崩解速度和更高的溶出速率。