The cephalosporin antibiotic cefuroxime axetil is a prodrug primarily absorbed from the upper part of the GIT and degraded in presence of intestinal esterases. The purpose of this investigation was to apply Box behnken response surface methodology for the development of a gastro retentive floating tablets of cefuroxime axetil and to inspect the effect of formulation variables on drug release and the buoyancy properties of the delivery system.
The amount of methocel K4M, cetyl alcohol and sodium bicarbonate were taken as independent variables and floating lag time, Q12h and t50% were taken as dependent variables. Tablets were prepared by the direct compression method and evaluated for physical properties, swelling, floating lag time, drug release. In vivo floating study also done on statistically optimized formulation in healthy male rabbit.
The duration of floating time were principally >24 hours and floating lag times <29 seconds. FTIR, DSC and diastereomeric ratio of the SOF revealed there was no chemical interaction between drug and polymer. The statistically optimized formulation (SOF) released drug according to zero order kinetics with a fickian diffusion mechanism. The in vivo evaluation of SOF in healthy rabbit showed that the tablet was buoyant in gastric fluid with change in its swelling.
Key words: Box behnken design (BBD), Response surface methodology, Cefuroxime axetil, Gastroretentive drug delivery, Optimization, Independent Variables, Dependent Variables.
Conventional oral dosage forms present no control over drug delivery leading to fluctuations in plasma drug concentration (Dhole et al., 2011). Oral controlled drug delivery is the majority preferable route of drug delivery due to the ease of administration, patient compliance and flexibility in formulation (Patil et al., 2011).
The bioavailability of the drug is influenced by several factors. One of the major factors is gastric emptying time (Desai and Bolton, 1993). The variability of the gastric emptying time leads to incomplete absorption of drug form the drug delivery system leading to reduce the efficacy of administered dose (Chueh et al., 1995).
The floating drug delivery system is one of the gastro retentive drug delivery system particularly useful for drugs which: a) are absorbed primarily in the stomach, b) are less soluble or are degraded by alkaline pH, c) have a narrow window of absorption, d) are metabolised by intestinal esterases, e) act locally in the stomach (Tiwari et al., 2012).
This paper states the formulation and optimization of an gastro retentive floating tablets to enhance the bioavailability by prolonging gastric retention. In the present investigation cefuroxime axetil was selected as a model drug in the development of Gastro retentive floating tablet (GRFT). Cefuroxime axetil is a 2nd generation cephalosporin available in conventional dosage forms for oral delivery and is considered as a broad spectrum...