Statistical optimization of floating-bioadhesive drug delivery system for risedronate sodium: In vitro, ex vivo and in vivo evaluation
Keywords:
Floating-bioadhesive tablets, Central composite design, Design of Expert, In vitro buoyancy, Ex-vivo bioadhesion, In vivo gastric residence timeAbstract
The objective of the present investigation was to apply statistical design for the development of risedronate sodium floating-bioadhesive tablets (RSFBT) employing response surface methodology (RSM). A central composite design (CCD) was developed using Design of Expert (DOE) software to study the effect of formulation variables on the drug delivery system. The RSFBT were prepared by direct compression using hydroxy propyl methyl cellulose (HPMC K100M) as release retardant; carbopol (CP 974P) as bioadhesive polymer and sodium bicarbonate (NaHCO3) as a gas-former. The quantities of HPMC K100M (X1), CP 974P (X2) and NaHCO3 (X3) were taken as independent variables and percentage drug release at 2 h (Q2), 6 h (Q6) and 12 h (Q12), floating lag time (FLT), total floating time (TFT) and bioadhesive strength (BS) were selected as responses. The BS was determined using porcine gastric mucosa. In all 15 formulations were prepared and studied. The results of the CCD indicated that high levels of both X1 and X3, and low level of X2 were required for the preparation of RSFBT. Further, a good correlation was observed between predicted and experimental values of the independent variables selected for this study. The drug release profiles of all the formulations were fitted into zero-order, first-order, Higuchi and Peppas models. The optimized formulation followed the Peppas model with a non-Fickian diffusion mechanism. The statistically optimized formulation (RSFBTsopt) was found to be physically stable when stored at 40 μ 2 oC/75 μ 5% RH for 3 months. In vivo evaluation of RSFBTsopt, BaSO4-loaded tablets revealed a mean gastric retention time of 5 μ 0.86 h (n=3) in healthy volunteers.
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