title: Development and in vitro evaluation of oral controlled release formulations of celecoxib using optimization techniques.
abstract: The objective of this study was to develop controlled release matrix embedded formulations of celecoxib (CCX) as candidate drug using hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose (EC), either alone or in combination, using optimization techniques like polynomial method and composite design. This would enable development of controlled release formulations with predictable and better release characteristics in lesser number of trials. Controlled release matrix tablets of CCX were prepared by wet granulation method. The in vitro release rate studies were carried out in USP dissolution apparatus (paddle method) in 900 ml of sodium phosphate buffer (pH 7.4) with 1% v/v tween-80. The in vitro drug release data was suitably transformed and used to develop mathematical models using first order polynomial equation and composite design techniques of optimization. In the formulations prepared using HPMC alone, the release rate decreased as the polymer proportion in the matrix base was increased. Whereas in case of formulations prepared using EC alone, only marginal difference was observed in the release rate upon increasing the polymer proportion. In case of formulations containing combination of HPMC and EC, the release of the drug was found to be dependent on the relative proportions of HPMC and EC used in the tablet matrix. The release of the drug from these formulations was extended up to 21 h indicating they can serve as once daily controlled release formulations for CCX. Mathematical analysis of the release kinetics indicates a near approximate Fickian release character for most of the designed formulations. Mathematical equation developed by transforming the in vitro release data using composite design model showed better correlation between observed and predicted t(50%) (time required for 50% of the drug release) when compared to first order polynomial equation model. The equation thus developed can be used to predict the release characteristics of the drug from matrix embedded formulations depending upon the proportion of HPMC and EC used in the formulation.
authors.affiliation: Formulation Development & Pharmacokinetic Laboratory, Pharmacy Group, Birla Institute of Technology & Science, Pilani, India. sajeev@bits-pilani.ac.in
authors.forename: Sajeev
authors.initials: S
authors.lastname: Chandran
authors.forename: Punnarao
authors.initials: P
authors.lastname: Ravi
authors.forename: Ranendra N
authors.initials: RN
authors.lastname: Saha
mesh_terms: D000068579:Celecoxib; D002482:Cellulose / Q000031:analogs & derivatives; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D007785:Lactose / Q000031:analogs & derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives; D011720:Pyrazoles; D012995:Solubility; D013449:Sulfonamides; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D003692:Delayed-Action Preparations; D011720:Pyrazoles; D013449:Sulfonamides; D013607:Tablets; C509290:hydroxypropylmethylcellulose-lactose matrix; C013517:ethyl cellulose; D002482:Cellulose; D008747:Methylcellulose; D007785:Lactose; D000068579:Celecoxib