FORMULATION DEVELOPMENT AND OPTIMIZATION OF EMPAGLIFLOZIN FILM COATED  TABLET USING QUALITY-BY-DESIGN APPROACH

SHRADDHA LAKAMBARE; ATUL PHATAK; MAHESH BHADAGALE; VARDHAMAN BAFNA

doi:10.22159/ajpcr.2023.v16i1.46037

Authors

SHRADDHA LAKAMBARE Department of Pharmaceutics, P. E. Society’s Modern College of Pharmacy, Pune, Maharashtra, India
ATUL PHATAK Department of Pharmaceutics, P. E. Society’s Modern College of Pharmacy, Pune, Maharashtra, India
Mahesh Bhadagale Callidus Research Laboratory, Pune, Maharashtra, India
VARDHAMAN BAFNA Callidus Research Laboratory, Pune, Maharashtra, India

DOI:

https://doi.org/10.22159/ajpcr.2023.v16i1.46037

Keywords:

Empagliflozin, in-vitro dissolution, film coated tablet, critical quality attributes

Abstract

Objective: Development of robust and effective oral solid immediate release film coated tablet of empagliflozin using Quality-by-Design (QbD) approach was the objective of present research work. This belongs to Sodium Glucose Co-Transporter-2 inhibitors-oral hypoglycemic class to treat Type-2 diabetes mellitus and associated cardiovascular comorbidities.

Methods: Assessment of risk factors (using Ishikawa fishbone diagram) was done by in-depth understanding of quality target product profile and critical quality attributes (CQAs) associated with material and process with justification. Randomized regular two levels full factorial design in addition with 5-center points was employed as Design of Experiment (DoE) tool. In this design, independent factors were concentrations of hydroxyl propyl cellulose (HPC SL) and croscarmellose sodium in mg. The responses selected for study were % drug release at 15-min in vitro dissolution time, disintegration time in sec, and hardness in Newton.

Results: ANOVA and lack-of-fit demonstrated that stipulated independent variables have significant impact on response variables and best correlation was seen in actual and predicted value. This optimization method confirmed that HPC SL (8 mg) and croscarmellose sodium (4 mg) were ideal concentrations of binder and disintegrant, respectively, to prepare said formulation with desired quality attributes and it was found to be better with respect to stability and effectiveness against marketed reference formulation.

Conclusion: QbD tools such as QTPP, CQAs, risk assessment, and DoE can be used in combination to optimize, screen, and understand the function of material and process parameters on quality characteristics of film-coated tablet.

Downloads

Download data is not yet available.

Author Biographies

ATUL PHATAK, Department of Pharmaceutics, P. E. Society’s Modern College of Pharmacy, Pune, Maharashtra, India

Professor and head of dept. of pharmaceutics ,P. E. Society’s Modern College of Pharmacy, Nigdi, Pune 411044, Maharashtra, India

Mahesh Bhadagale, Callidus Research Laboratory, Pune, Maharashtra, India

Head of formulation research development dept, Callidus Research Laboratory, Nighoje, Pune 410501, Maharashtra, India

References

Khan MA, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of Type 2 diabetes-global burden of disease and forecasted trends. J Epidemiol Glob Health 2020;10:107-11.

Tsushima Y, Lansang MC, Makin V. The role of SGLT-2 inhibitors in managing Type 2 diabetes. Cleve Clin J Med 2021;88:47-59.

Kalra S. Sodium glucose co-transporter-2 (SGLT2) inhibitors : A review of their basic and clinical pharmacology. Diabetes Ther 2014;2:355-66.

Dalama B, Mesa J. New oral hypoglycemic agents and cardiovascular risk. Crossing the metabolic border. Rev Esp Cardiol (Engl Ed) 2016;69:1088-97.

Zhang L, Mao S. Application of quality by design in the current drug development. Asian J Pharm Sci 2017;12:1-8.

ICH. Q8(R2) Guideline Pharmaceutical Development, Current Step 4 Version. Switzerland: International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use; 2009.

Phatak A, Joshi D, Bhadgale M, Chaudhari P. Development and optimization of naproxen sodium controlled release tablets : QbD approach. Indian J Pharm Educ Res 2020;54(2s):s108-16.

FDA CDER Guidance for Industry. Dissolution Testing and Specification Criteria for Immediate-Release Solid Oral Dosage Forms Containing Biopharmaceutics Classification System Class 1 and 3 Drugs Guidance for Industry Dissolution Testing and Specification Criteria for Immediate-Release. United States: Food and Drug Administration; 2015.

ICH. Q1A(R2) Guideline Stability Testing of New Drug Substances and Products, Current Step 4 Version. Switzerland: International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use; 2003.

Mishra SM, Rohera BD. An integrated, quality by design (QbD) approach for design, development and optimization of orally disintegrating tablet formulation of carbamazepine. Pharm Dev Technol 2017;22:889-903.