Preparation of Size Controlled Poly (D, L) Lactide Nanoparticles by Modified Nanoprecipitation Technique:Optimization Using Quality by Design Concept

Abstract

Poly (D, L) lactide (PLA) based nanoparticulate carriers attracted pharmaceutical formulator for delivery of bioactive agents owing to its biocompatibility, biodegradability and outstanding controlled release characteristics. The objective of this study was the preparation, physico-chemical characterization and statistical optimization of size controlled PLA nanoparticles by modified nanoprecipitation technique. Preliminary experiments suggested that particle size as well as process yield of PLA nanoparticles were affected by number of formulation as well as process parameters. But it was difficult to identify critical quality attributes which significantly affect particle size and process yield amongst the large number of variables. Hence in current research attempts have been made to identify critical quality attributes by exploration of statistical screening design i.e. 27-4 fractional factorial design. Concentration of stabilizer i.e. tween 20 and type of external phase emerged as critical formulation parameters from the screening experiments. Hence, in further investigation a 32 full factorial design was used to investigate the combined influence of concentration of tween 20 (X1) and type of external phase (X2) on particle size (Y1) and process yield (Y2). The nanoparticles were also evaluated for particle size distribution and zeta potential. Statistically significant model were evolved to predict entrapment efficiency and particle size. The effect of factor X1, X2 and X12 were found to be statistically significant in nature. Response variables i.e. particle size and process yield were simultaneously optimized using desirability function using Design Expert software. This process allowed selection of most suitable level of factors to achieve desired level of particle size and process yield. The results of multiple linear regression analysis revealed that for obtaining desirable particle size (less than 150 nm) and process yield (more than 80 %), the nanoparticles should be prepared using 0.3 % w/v of tween 20 and water : ethanol (75: 25) as a external phase. In conclusion, results of the present study demonstrated that PLA nanoparticles with expected particle size and process yield can be obtained by adopting the concept of quality by design.