Design And Development Of Generic Formulation By Applying Reverse Engineering Approach

Abstract

Introduction: The innovator formulation is meat for its high cost as Innovator Company used to invest millions of dollars. The generic formulation is an alternative to beat the cost. The criteria of generic formulation is should have the bioequivalence as that of RLD (Reference Listed Drug). Reverse engineering is decoding of the RLD to find out qualitative and quantitative composition. Rationale behind reverse engineering is if qualitative and quantitative composition of the formulations is same then performance of the formulation will also be same. That helps to speed up the process of generic formulation development and reduces cost and time. The formulation used in study is anti-opioid uni-dose nasal spray 4mg/0.1ml. The formulation contains of anti-opioid drug, benzoalkonium chloride(BKC), EDTA, sodium chloride (NaCl) and pH adjusters like hydrochloric acid, sodium hydroxide.

Objectives: The main objective of current research is to perform reverse engineering of RLD to find out the qualitative and quantitative composition by using different analytical methods and validate the same as per ICH guideline. To develop generic formulation by using data obtained from reverse engineering. To perform similarity matrixing for in-house and RLD formulation.

Methods: Different analytical methods were used to perform the reverse engineering of the RLD to find out the qualitative and quantitative composition like HPLC for benzoalkonium chloride and EDTA. Flame photometry for the NaCl, and the Nano-drop UV for the Anti-opioid drug. The Assay, pH, osmolarity and viscosity were performed for complete characterization of the RLD while for in-house to show the similarity matrixing.

Results: The de-formulation was performed for all the components and the methods were validated as per ICH guideline. The correlation coefficient was >0.99 for all components in all the methods. The recovery results ranged from 99.4 to 99.6% for anti-opioid drug, 99.83−100.33% for BKC, 100.02−100.23% for NaCl and 100.3−100.7% for EDTA. The obtained % RSD for precision study were 0.87% (intraday) and 0.76% (interday) for anti-opioid drug, 0.01% (intraday) and 0.1 (interday) for BKC, 0.62% (intraday) and 0.54 (interday) for NaCl and 0.62%(intraday) and 0.54 (interday) for EDTA. There were no interference of other components and methods are specific.

Conclusions: The reverse engineering gave critical information about the formulation apart from qualitative and quantitative composition like process used by innovator to stabilize the formulation, viscosity of formulation and mechanism of uni-dose nasal spray to provide the better efficacy. That saves time, cost and manpower incurred for the trial batches. The validation of methods gave an assurance for the qualitative and quantitative composition helped for getting affordable bioequivalent generic formulation.