QUALITY BY DESIGN BASED DEVELOPMENT OF ETRAVIRINE SELF MICRO EMULSIFYING DRUG DELIVERY SYSTEM
Keywords:Bioavailability, Etravirine, Risk Assessment, SMEDDS, QbD
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.
Jadhav JB, Girawale NN, Chaudhari RA. Quality by design (QBD) approach used in development of pharmaceuticals. Int J Pure Appl Biosci 2014;2:214-3.
Lawrence XY, Amidon G, Khan MA, Hoag SW, Polli J, Raju GK, Woodcock J. Understanding pharmaceutical quality by design. AAPS J 2014;16:771-83.
Lawrence XY. Pharmaceutical quality by design: product and process development, understanding, and control. Pharm Res 2008;25:781-91.
Scholler Gyure M, Kakuda TN, Raoof A, De Smedt G, Hoetelmans RM. Clinical pharmacokinetics and pharmacodynamics of etravirine. Clin Pharmacokinet 2009;48:561-74.
Kakuda TN, Schöller Gyüre M, Hoetelmans RM. Pharmacokinetic interactions between etravirine and non-antiretroviral drugs. Clin Pharmacokinet 2011;50:25-39.
Wang L, Dong J, Chen J, Eastoe J, Li X. Design and optimization of a new self-nano emulsifying drug delivery system. J Colloid Interf Sci 2009;330:443-8.
Kassem AM, Ibrahim HM, Samy AM. Development and optimization of atorvastatin calcium loaded self-nanoemulsifying drug delivery system (SNEDDS) for enhancing oral bioavailability: in vitro and in vivo evaluation. J Microencapsul 2017;34:319-33.
Nasr AM, Gardouh AR, Ghonaim HM, Ghorab MM. Design, formulation and in vitro characterization of irbesartan solid self-nanoemulsifying drug delivery system (S-SNEDDS) prepared using spray drying technique. J Chem Pharm Res 2016;8:159-83.
Beg S, Sandhu PS, Batra RS, Khurana RK, Singh B. QbD-based systematic development of novel optimized solid self-nanoemulsifying drug delivery systems (SNEDDS) of lovastatin with enhanced biopharmaceutical performance. Drug Delivery 201518;22:765-84.
Herneisey M, Lambert E, Kachel A, Shychuck E, Drennen JK, Janjic JM. Quality by design approach using multiple linear and logistic regression modeling enables microemulsion scale up. Molecules 2019;24:1-20.
Kalamkar R, Wadher S. Design and optimization of novel self nano emulsifying formulation of Etodolac. Int Res J Pharm 2018;9:85-90.
Reddy MS, Rambabu B, Vijetha KA. Development and evaluation of solid self nano emulsifying drug delivery system of poorly soluble olmesartan medoxomil by using adsorption on to solid carrier technique. Int J Pharm Sci Res 2018;9:3398-407.
Cafaggi S, Leardi R, Parodi B, Caviglioli G, Bignardi G. An example of application of a mixture design with constraints to a pharmaceutical formulation. Chemom Intell Lab Syst 2003;65:139-47.
Truong DH, Tran TH, Ramasamy T, Choi JY, Lee HH, Moon C, et al. Development of solid self-emulsifying formulation for improving the oral bioavailability of erlotinib. AAPS PharmSciTech 2016;17:466-73.
Saritha D, Bose P, Nagaraju R. Formulation and evaluation of self-emulsifying drug delivery system (SEDDS) of Ibuprofen. Int J Pharm Sci Res 2014;5:3511-9.
Sahoo SK, Suresh P, Acharya U. Design and development of self-microemulsifying drug delivery systems (SMEDDS) of telmisartan for enhancement of in vitro dissolution and oral bioavailability in rabbit. Int J Appl Pharm 2018;10:117-26.
Islambulchilar Z, Valizadeh H, Zakeri Milani P. Systematic development of DoE optimized SNEDDS of sirolimus with enhanced intestinal absorption. J Drug Delivery Sci Technol 2014;24:620-7.
Chintalapudi R, Murthy TE, Lakshmi KR, Manohar GG. Formulation, optimization and evaluation of self-emulsifying drug delivery systems of nevirapine. Int J Pharm Investig 2015;5:205-13.
Dissolution methods Database. U. S. Food and Drug Administration. Available from: https://www. accessdata.fda.gov/scripts/cder/dissolution/dspsearch result.cfm [Last accessed on 07 Jan 2020]
Preethi GB, Shivakumar HN, Ravi Kumar M, Sweta N. Prototype self emulsifying system of etravirine: design, formulation and in vitro evaluation. Int J Appl Pharm 2018;10:13-9.