Formulation Development and Optimization of Intermediate Release Metoclopramide HCl Tablets by Central Composite Rotatable Design for IVIVC Studies
Ahmad Khan1, Jallat Khan2, Maria Zafar3, Muhammad Irfan4, Imran Rabbani5
1Ahmad Khan* , Department of Pharmacy, Quaid I Azam University, Islamabad, Pakistan.
2Jallat Khan, Department of Chemistry Islamia University Bahawalpur, Pakistan.
3Maria Zafar, Department of Pharmacy, Quaid I Azam University, Islamabad, Pakistan.
4Muhammad Irfan, Department of Pharmacy GC University Faisalabad, Pakistan.
5Imran Rabbani, Department of Pharmacy, Kohat University of of Science and Technology Kohat, Pakistan.

Manuscript received on January 02 2015. | Revised Manuscript received on January 08, 2015. | Manuscript published on January 15, 2015. | PP: 21-30 | Volume-3 Issue-2, January 2015. | Retrieval Number: A0763123114/2014©BEIESP
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Abstract: The objective of this study was development and optimization of intermediate release formulation for IVIVC study of metoclopramide HCl. A four steps simple and cost effective study was performed. The first step was to study the micromeritic properties of different powder blends with and without metoclopramide HCl (Placebo). In second and third step, central composite design (CCRD) was used for intermediate release metoclopramide tablets. In the last step stability studies of three selected metoclopramide HCl tablet formulations which were calculated using R Gui software. Varying concentrations of excipients, HPMC K4M cps, Avicel PH-102, and lactose DC were used as variables in CCRD. Preformulation studies of two blended powders i.e. placebo and metoclopramide HCl were done to evaluate the angle of repose, loose bulk density, tapped bulk density, and compressibility index. Blending rate constant was performed at different mixing times i.e. 5, 7, 12, and 15 minutes. Out of twenty intermediate release formulations, three (F1, F7, F10) were subjected to direct compression on the basis of compressibility index. Physicochemical properties and in-vitro kinetic studies in different dissolution media were measured successfully. Simple experimental studies were performed to determine relative densities, tensile strength of tablets, hardness, weight variation, friability, disintegration and dissolution of tablets. Presence of metoclopramide HCl in the powder blend enhanced all the micromeritics properties. 12 minutes was found to be the best mixing time. The increase in relative density resulted in increase in hardness of tablets containing metoclopramide HCl. The analysis of release pattern was done using model dependent kinetic approaches i.e. zero order kinetics, first order kinetics, Hixon Crowell, Higuchi kinetics, Korsmeyer and pappas, Baker and Lonsdale model, Weibull model, Hopfenberg model and peppas Sahlin model; and model independent kinetic models using f1 and f2 values. F10 showed the best result in stability studies having shelf life of 64 months calculated by RGui.
Keywords: Metoclopramide HCl, Intermediate release, stability studies, central composite design, model dependent and model independent kinetic models.