Title:Pharmaceutical Product Lead Optimization for Better In vivo Bioequivalence Performance: A case study of Diclofenac Sodium Extended Release Matrix Tablets
Volume: 15
Issue: 5
Author(s): Aliasgar Shahiwala*Aisha Zarar
Affiliation:
- Department of Pharmaceutics, Dubai Pharmacy College, Dubai,United Arab Emirates
Keywords:
bioequivalence, biowaiver, convolution, diclofenac sodium, drug release kinetics, extended release, generic product
development, in vivo-in vitro correlations, natural polymers.
Abstract: Background: In order to prove the validity of a new formulation, a considerable amount of
effort is required to study bioequivalence, which not only increases the burden of carrying out a number
of bioequivalence studies but also eventually increases the cost of the optimization process.
Objective: The aim of the present study was to develop sustained release matrix tablets containing diclofenac
sodium using natural polymers and to demonstrate step by step process of product development
till the prediction of in vivo marketed product equivalence of the developed product.
Method: Different batches of tablets were prepared by direct compression. In vitro drug release studies
were performed as per USP. The drug release data were assessed using model-dependent, modelindependent
and convolution approaches.
Results: Drug release profiles showed that extended release action were in the following order: Gum
Tragacanth > Sodium Alginate > Gum Acacia. Amongst the different batches prepared, only F1 and F8
passed the USP criteria of drug release. Developed formulas were found to fit Higuchi kinetics model
with Fickian (case I) diffusion-mediated release mechanism. Model- independent kinetics confirmed
that total of four batches were passed depending on the similarity factors based on the comparison with
the marketed Diclofenac. The results of in vivo predictive convolution model indicated that predicted
AUC, Cmax and Tmax values for batch F8 were similar to that of marketed product.
Conclusion: This study provides simple yet effective outline of pharmaceutical product development
process that will minimize the formulation development trials and maximize the product success in
bioequivalence studies.