Patel Kunal N, Mehta Tejal A
Department of Pharmaceutics, Nirma Institute of Pharmacy, Gujarat, India.
Department of Pharmaceutics, Nirma Institute of Pharmacy, Gujarat, India
PDA J Pharm Sci Technol. 2014 Jul-Aug;68(4):333-46. doi: 10.5731/pdajpst.2014.00984.
Elementary osmotic pumps are well known for delivering moderately soluble drugs at a zero-order rate. The objective of the present study was to develop elementary osmotic pump tablets containing Flurbiprofen using an inclusion complex. Formation of complex was confirmed by Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy. A 3(2) factorial design was applied systematically; the amount of osmotic agent (X1) and size of delivery orifice (X2) were selected as independent variables. Batches were prepared by the direct compression method and evaluated for percent cumulative drug release (%CDR) at 9 h as dependent variables. The amount of osmotic agent and size of the delivery orifice had a significant effect on %CDR. The results of multiple linear regression analysis revealed that elementary osmotic pump tablets should be prepared using an optimum concentration of osmotic agent and size of delivery orifice to achieve a zero-order drug release. Contour plots as well as response surface plots were constructed to show the effects of X1 and X2 on %CDR. A model was validated for accurate prediction of %CDR by performing checkpoint analysis. The computer optimization process, contour plots, and response surface plots were predicted at the concentration of independent variables X1 and X2 (78.38 mg and 0.99 mm, respectively), for maximized response. The drug release from the developed formulation was found to be independent of pH and agitational intensity. The above optimized batch was also evaluated by different pharmacokinetic models like zero-order, first-order, Higuchi, Korsmeyer Peppas, and Hixson Crowell models. Stability study of the optimized batch was conducted at accelerated conditions for 6 months, and was found stable. This study strongly indicates application of osmotic tablets of Flurbiprofen for the treatment of rheumatoid arthritis, as well as osteoarthritis.
The aim of this study was to develop an elementary osmotic pump tablet of Flurbiprofen and to deliver the drug at a zero-order rate. Elementary osmotic pumps are well known for delivering moderately soluble drugs at a zero-order rate. Elementary osmotic pump tablets containing an inclusion complex of Flurbiprofen was prepared by the direct compression method. The amount of osmotic agent and size of delivery orifice were selected as independent variables. Percent cumulative drug release at 9 h was evaluated for all batches, and it was found that amount of osmotic agent and size of delivery orifice had a significant effect on percent cumulative drug release. The drug release from the developed formulation was found to be independent of pH and agitational intensity. It was also observed that the optimized formulation followed zero-order kinetics and was stable for 6 months at accelerated conditions.
基本渗透泵以零级速率递送中度溶解性药物而闻名。本研究的目的是开发含有氟比洛芬的包合物的基本渗透泵片。通过差示扫描量热法和傅里叶变换红外光谱法确认了包合物的形成。系统地应用了3（2）析因设计；选择渗透剂的量（X1）和释药孔的尺寸（X2）作为自变量。通过直接压片法制备批次，并以9小时的累积药物释放百分比（%CDR）作为因变量进行评估。渗透剂的量和释药孔的尺寸对%CDR有显著影响。多元线性回归分析结果表明，应使用最佳浓度的渗透剂和释药孔尺寸来制备基本渗透泵片，以实现药物的零级释放。构建等高线图以及响应面图以显示X1和X2对%CDR的影响。通过进行检查点分析验证了一个模型对%CDR的准确预测。在自变量X1和X2的浓度（分别为78.38毫克和0.99毫米）下预测了计算机优化过程、等高线图和响应面图，以实现最大化响应。发现所开发制剂的药物释放与pH值和搅拌强度无关。上述优化批次还通过零级、一级、Higuchi、Korsmeyer Peppas和Hixson Crowell等不同药代动力学模型进行了评估。在加速条件下对优化批次进行了6个月的稳定性研究，发现其稳定。本研究强烈表明氟比洛芬渗透片可用于治疗类风湿性关节炎以及骨关节炎。
本研究的目的是开发一种氟比洛芬基本渗透泵片，并以零级速率递送药物。基本渗透泵以零级速率递送中度溶解性药物而闻名。通过直接压片法制备了含有氟比洛芬包合物的基本渗透泵片。选择渗透剂的量和释药孔的尺寸作为自变量。对所有批次评估9小时的累积药物释放百分比，发现渗透剂的量和释药孔的尺寸对累积药物释放百分比有显著影响。发现所开发制剂的药物释放与pH值和搅拌强度无关。还观察到优化制剂遵循零级动力学，并且在加速条件下6个月稳定。
