BIORELEVANT DISSOLUTION METHOD DEVELOPMENT OF MEMANTINE EXTENDED-RELEASE CAPSULES FOR PREDICTION OF PRE-PRANDIAL IN-VIVO PERFORMANCE

The main objective of this research work is to develop biorelevant dissolution method for the Memantine extended-release capsule by correlating pre-prandial in-vivo performance. The mean plasma concentration profile obtained after oral administration of extended-release capsules was deconvoluted using the Wagner-Nelson deconvolution technique for deriving the percentage fraction of drug absorbed to achieve the target dissolution profile. The dissolution results obtained by using the office of generic drugs recommended dissolution method was not comparable with the target dissolution profile and observed with an F₂ value of 30. Biorelevant dissolution method was developed using USP Apparatus 3 (reciprocating cylinder), with dissolution media simulating gastrointestinal tract sink condition. A full factorial design of the experiment was carried out for dissolution method development and optimization. Media volume and dips per minute were considered as main factors in the design of the experimental study. The developed biorelevant dissolution method based on statistical interpretation of the main effect, interaction effect, and desirability factor is with media volume 150 ml and 15 dips per minute and observed with the F₂ value (similarity factor) of 90. The developed dissolution method demonstrates a very good in-vitro/in-vivo correlation under the pre-prandial condition and observed with R² value of 0.998. The dissolution method shall be used as a predictive in-vitro tool for evaluation Memantine extended-release capsules, and also gives the advantage of claiming bio-waiver.