QUALITY BY DESIGN BASED DEVELOPMENT OF ETRAVIRINE SELF MICRO EMULSIFYING DRUG DELIVERY SYSTEM
Objective: The main objective of the present research work was to develop systematically the Self Micro Emulsifying Drug Delivery system of BCS Class IV drug in a Quality by Design framework.
Methods: The quality by design-based formulation development proceeds with defining the Quality Target Product Profile and Critical Quality Attributes of dosage form with appropriate justification for the same. The statistical Mixture design was used for the development of the formulation. The independent variables selected for the design were Oleic acid, Labrasol and PEG 6000, whereas droplet size (nm), emulsification time (sec), % drug loading and % drug release at 15 min were considered as the potential quality attributes of the Self Micro Emulsifying System. The eight different batches of Etravirine-Self Micro Emulsifying systems (ETV-SMEDDS) were prepared and checked for the Critical Quality Attributes. The simultaneous optimization of the formulation was done by the global desirability approach.
Results: The characterization report obtained for all the different batches of formulation was analyzed statistically by fitting into regression models. The statistically significant models determined for droplet size (nm) (R2= 0.96 and p-0.1022), emulsification time (sec) (R2= 0.99 and p-0.0267), % drug loading (R2= 0.93 and p-0.1667) and % drug release at 15 min (R2= 0.96 and p-0.0911) and were statistically significant. The maximal global desirability value obtained was 0.9415 and the value indicates, the selected factors and responses have a good correlation and are significant enough for optimization and prediction of best formulation.
Conclusion: The QbD approach utilized during the development of ETV-SMEEDS facilitated the identification of Critical Material Attributes and their significant impact on the Critical Quality Attributes of SMEDDS. The concept of building quality into product through the QbD application was utilized successfully in the formulation development.
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