Lakshmi K, Reddy M Pranav Kumar, Kaza Rajesh
Department of Pharmaceutics, Sri Padmavathi School of Pharmacy, Vaishnavi Nagar, Tiruchanoor, Tirupati 517503, India.
Curr Drug Discov Technol. 2013 Dec;10(4):305-14. doi: 10.2174/15701638113109990035.
Poor aqueous solubility and bioavailability of drugs are one of the important factors affecting the absorption of drugs and consequently their therapeutic effectiveness. Celecoxib is a widely used anti-inflammatory agent, with special use in rheumatoid arthritis. It belongs to biopharmaceutical classification system (BCS) class II drug with low solubility and high permeability. The present study was aimed to prepare and characterize the microcrystals of celecoxib, employing in situ micronization technique by rapid solvent change approach to enhance the solubility and dissolution rate and to optimize the solvent and anti-solvent ratio (v/v) using hydrophilic stabilizers such as guar gum, maltodextrin and PVP K30. The prepared formulations were evaluated for percentage crystal yield, mean particle size, drug content and in vitro dissolution studies. Amongst the formulations prepared (F1-F9), F6 formulation containing maltodextrin as stabilizing agent at 0.1% w/v concentration with 1:6 ratio of solvent to anti-solvent (v/v) respectively was considered as optimized formulation in which percentage drug release was found to be 89.33% within 60 minutes in comparison with that of the pure drug dissolution of 30.26% only within 60 minutes. Characterization studies like SEM, DSC and XRD indicate the solubility enhancement of celecoxib microcrystals due to decrease in particle size when compared to that of pure drug. FT-IR spectroscopy studies revealed that there is no chemical interaction between the drug and stabilizer and crystalline habit modification occurs in the microcrystals without any polymorphic changes.
药物的低水溶性和低生物利用度是影响药物吸收并进而影响其治疗效果的重要因素之一。塞来昔布是一种广泛使用的抗炎药，在类风湿性关节炎治疗中具有特殊用途。它属于生物药剂学分类系统（BCS）中的II类药物，具有低溶解性和高渗透性。本研究旨在制备塞来昔布微晶并对其进行表征，采用快速溶剂变化法通过原位微粉化技术来提高其溶解度和溶出速率，并使用瓜尔胶、麦芽糊精和聚乙烯吡咯烷酮K30（PVP K30）等亲水性稳定剂优化溶剂与抗溶剂的比例（v/v）。对所制备的制剂进行晶体产率百分比、平均粒径、药物含量和体外溶出度研究。在所制备的制剂（F1 - F9）中，F6制剂含有浓度为0.1% w/v的麦芽糊精作为稳定剂，溶剂与抗溶剂的比例分别为1:6（v/v），该制剂被认为是优化制剂，其中在60分钟内药物释放百分比为89.33%，而纯药物在60分钟内的溶出度仅为30.26%。扫描电子显微镜（SEM）、差示扫描量热法（DSC）和X射线衍射（XRD）等表征研究表明，与纯药物相比，塞来昔布微晶由于粒径减小而溶解度提高。傅里叶变换红外光谱（FT - IR）研究表明，药物与稳定剂之间不存在化学相互作用，微晶中发生了晶习改变但没有任何多晶型变化。
