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The research was featured to formulate, characterise and optimise the Azithromycin Proniosome using the three-factor three-level Box Behnken scheme. The independent variables chosen were span 20 (X1), span 80 (X2) and phospholipids (X3) to assess their individual and shared response on entrapment efficiency (Y1) and % drug released at six h (Y2). Based on Box Behnken design, 15 formulations were prepared and optimised using Design Expert Version 22.214.171.124. The entrapment efficiency and in-vitro drug release were exposed to different regressions to setup a polynomial equation. The counterplots understood the connections between the independent and dependent factors. The congruity of the polynomial equations was tested by fixing three checkpoint groups. The optimised formulation was determined by point prediction method using the various constraints. The optimised batch was subjected to multiple parameters such as vesicle shape, viscosity, spread ability, drug content, entrapment efficiency, in-vitro drug diffusion and stability studies. The optimised formulation shows better physical and chemical stability which is confirmed by the results of various parameters. The in-vitro drug diffusion has observed to be 98.53% at 24th h obeying zero-order drug release with diffusion mediated non-fickian type of drug release kinetics. The formulation preserved at both refrigerated and room temperature shows better stability. This approach might be an additional finding in enhancing the adherence of patient and improves compliance.
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