Statistical optimization of a novel excipient (CMEC) based gastro retentive floating tablets of propranolol HCl and it’s in vivo buoyancy characterization in healthy human volunteers

Abstract

The objective of the present investigation is to formulate gastro retentive floating drug delivery systems (GRFDDS) of propranolol HCl by central composite design and to study the effect of formulation variables on floating lag time, D1hr (% drug release at 1 hr) and t90 (time required to release 90% of the drug). 3 factor central composite design was employed for the development of GRFDDS containing novel semi synthetic polymer carboxymethyl ethyl cellulose (CMEC) as a release retarding polymer. CMEC, sodium bicarbonate and Povidone concentrations were included as independent variables. The tablets were prepared by direct compression method and were evaluated for in vitro buoyancy and dissolution studies. From the polynomial model fitting statistical analysis, it was confirmed that the response floating lag time and D1hr is suggested to quadratic model and t90 is suggested to linear model. All the statistical formulations followed first order rate kinetics with non-Fickian diffusion mechanism. The desirability function was used to optimize the response variables, each having a different target, and the observed responses were highly agreed with experimental values. Statistically optimized formulation was characterized by FTIR and DSC studies and found no interactions between drug and polymer. The results demonstrate the feasibility of the model in the development of GRFDDS containing a propranolol HCl. Statistically optimized formulation was evaluated for in vivo buoyancy studies in healthy humans for both fed and fasted states. From the results, it was concluded that gastric residence time of the floating tablets were enhanced at fed stage but not in fasted state.

Design and statistical optimization of an effervescent floating drug delivery system of theophylline using response surface methodology

“…Drug retarding ability is aff ected by the molecular weight of the polymer (18). Higher molecular weight polymers retarded the drug more effi ciently than polymers with lower molecular weight (12).…”

“…The samples were analyzed using a UV spectrophotometer at 270 nm. The in vitro dissolution studies were triplicated for all batches (18).…”

“…When in contact with gastric fl uid, sodium bicarbonate will liberate carbon dioxide gas (16,17). The gas entrapped within the matrix decreases the density of the tablet below 1 g cm -3 , providing buoyancy to the dosage form (16,18). While the system is fl oating in the gastric medium, the drug will be released slowly at a controlled rate without aff ecting the gastric emptying rate (7,19).…”

“…This results in the requirement for a large number of runs to achieve target responses (18). A statistical approach using response surface methodology (RSM) can be employed to optimize the formulation using a suitable experimental design such as central composite design (23).…”

Design, development and optimization of s (-) Atenolol floating sustained release matrix tablets using surface response methodology

“…These plots are useful in the study of effects of formulation factors on the response at one time and predict the responses of dependent variables at the intermediate levels of independent variables. Subsequently, a numerical optimization technique by the desirability approach and graphical optimization technique by the overlay plot were used to generate the new formulations with the desired responses[ 14 ].…”