Open AccessIMPLEMENTATION OF QUALITY BY DESIGN (QBD) APPROACH IN FORMULATION AND DEVELOPMENT OF RITONAVIR PELLETS USING EXTRUSION SPHERONIZATION METHOD
Author(s) -
Satish K Mandlik,
Payal P. Agarwal,
Harshal P. Dandgavhal
Publication year - 2019
Publication title -
international journal of applied pharmaceutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.238
H-Index - 15
ISSN - 0975-7058
DOI - 10.22159/ijap.2020v12i1.35453
Subject(s) - pellets , factorial experiment , extrusion , quality by design , critical quality attributes , ritonavir , materials science , dosage form , chromatography , fractional factorial design , pareto chart , mathematics , particle size , chemistry , medicine , human immunodeficiency virus (hiv) , chemical engineering , composite material , antiretroviral therapy , statistics , engineering , pareto principle , family medicine , viral load
Objective: Ritonavir is an antiretroviral drug used for HIV-AIDS treatment. The purpose of this research work was to implement the quality by design (QbD) approach in formulation of ritonavir sustained-release pellets by industrially applied extrusion spheronization technique.
Methods: Pellets were prepared by extrusion spheronization method and evaluated for their physicochemical properties. Initially, on the basis of prior knowledge Quality Target Product Profile (QTTP) element was identified and further Critical Quality Attributes (CQA) elements were defined. Risk assessment (RA) was done by two tools as failure mode and effect analysis (FMEA) and fishbone diagram (Ishikawa plot). Placket Burman design was implemented as a screening design using seven high-risk factors (spheronization speed, spheronization time, extrusion speed, drying method, PVP K 30, cross povidone, and solvent). Optimization study was done by 23 full factorial design with three critical factors as (spheronization speed, extrusion speed and PVP K 30). The in vitro drug release was studied in both gastric and intestinal fluids for 12 h using USP Ι apparatus. Control space was established for the sustained release pellets.
Results: Among all batches obtained in 23 full factorial design, batch R7 was found to be effective with carr’s index value of 5.281, percentage yield of 69.6%, time required to release 50% drug was 8 h and percent drug release after 12 h was found 83.132 %, R7 batch was selected as optimized batch. Statistical analysis showed model terms were significant.
Conclusion: We can conclude that; sustained-release pellets of ritonavir were successfully designed using QbD approach.