Development and <i>In vitro</i> 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 buŠer (pH 7.4) with 1％ v/v tween-80. The in vitro drug release data was suitably transformed and used to develop mathematical models usingˆrst 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 diŠerence 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 toˆrst 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.

Formulation of Sustained-Release Matrix Tablets Using Cross-linked Karaya Gum

“…This is in agreement with previous works which suggested that the viscosity of the gel layer around the drug particles in the tablet increases with increase in hydrogel concentration thus limiting the release of the drug [19]. The gel formed during the penetration of dissolution media into the matrix structure, consists of closely packed swollen particles.…”

Characterization of Celecoxib-Loaded Solid Lipid Nanoparticles Formulated with Tristearin and Softisan 100

“…For example, the release of CXB from cellulose mixture was extended up to 21 h in a biphasic fashion, with 50 % released between 75 and 140 h for ethyl cellulose and 2.8 to 6.5 h for HPMC [9]. Using a pharmacodynamic model, topical nanostructured lipid carrier gel of CXB showed faster onset and prolonged activity up to 24 h [10].…”

Poly(vinyl alcohol)‐based electrospun nanofibers for the sustained release of celecoxib: Characterization and evaluation of drug release mechanism

“…It is approximately 10–20 times more selective for COX‐2 inhibition than COX‐1 . Recent studies have indicated that the CX has a potential role for chemoprevention of various cancers . CX has a poor bioavailability due to its lipophilic feature (logP = 4.21) .…”

“…Also, this compound may cause cardiovascular events and to reduce the risk of cardiovascular events, it is suggested using the lowest effective dose for the shortest duration of time . So, the use of controlled release formulation of CX would be expected to increase bioavailability and improve patient compliance with fewer side effects .…”

“…Chandran et al used hydroxylpropyl methyl cellulose and ethyl cellulose for manufacturing controlled release tablets embedded oral formulation of CX. They investigated CX release into sodium phosphate buffer (pH 7.4) with tween 80 . Venkatesan et al studied the in vitro release of CX into HCl (pH 1.0) by using hydroxyapatite‐chitosan nanocomposite .…”