Statistical Design of Experiments on Fabrication of Bilayer Tablet of Narrow Absorption Window Drug: Development and In vitro characterisation

Abstract

The current study involves the fabrication of oral bioadhesive bilayer matrices of narrow absorption window drug baclofen and the optimisation of their in vitro drug release and characterisation. Statistical design of experiments, a computer-aided optimisation technique, was used to identify critical factors, their interactions and ideal process conditions that accomplish the targeted response(s). A central composite design was employed to systematically optimise the drug delivery containing a polymer, filler and compression force. The values of ratio of different grades of hydroxypropyl methylcellulose, microcrystalline cellulose and compression force were varied to be fitted in design. Drug release at 1 h (Q1), 4 h (Q4), 8 h (Q8), 12 h (Q12), and hardness were taken as responses. Tablets were prepared by direct compression methods. The compressed tablets were evaluated for their hardness, weight variation, friability, content uniformity and diameter. Counter plots were drawn and optimum formulation was selected by desirability function. The formulations were checked for their ex vivo mucoadhesion. The experimental value of Q1, Q4, Q8, Q12 and hardness for check-point batch was found to be 31.64, 45.82, 73.27, 98.95% and 4.4 kg/cm(2), respectively. The release profile indicates Highuchi kinetics (Fickian transport) mechanism. The results of the statistical analysis of the data demonstrated significant interactions amongst the formulation variables, and the desirability function was demonstrated to be a powerful tool to predict the optimal formulation for the bilayer tablet.

Keywords: Desirability function; narrow absorption window drug; statistical design of experiments.

Fig. 1

Contour plot showing percentage drug release at 1^st h. Contour plot showing percentage drug release at 1^st h (Q1) using different combination of B and C (A is constant). The contour lines show percentage drug release at the end of 1^st h

Fig. 2

Contour plots showing percentage drug release at 4 h (Q₄). Contour plots showing percentage drug release at 4 h (Q₄). (a) Using different combination of A and B (C is constant). (b) Using different combination of B and C (A is constant). The contour lines show percentage drug release at the end of 4 h

Fig. 3

Contour plot showing percentage drug release at 8 h (Q8). Contour plot showing percentage drug release at 8 h (Q8). (a) Using different combination of A and B (C is constant). (b) Using different combination of B and C (A is constant). The contour lines show percentage drug release at the end of 8 h

Fig. 4

Contour plot showing percentage drug release at 12 h (Q12). Contour plot showing percentage drug release at 12 h (Q12), Using different combination of A and B (C is constant). The contour lines show percentage drug release at the end of 12 h

Fig. 5

Contour plot showing hardness. Contour plot showing hardness using different combination of B and C (A is constant). The contour lines show hardness

Fig. 6

Ex vivo mucoadhesion study. Ex vivo mucoadhesion study of all central composite design formulation and optimized formulation RJ1

Fig. 7

3D Response surface for desirability. Response surface (3D) showing the effect of different combinations of A and B on desirability