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Quality-by-Design Approach for Optimization and Processing of PLGA Polymer Film by Hot Melt Extrusion

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Abstract

Purpose

The study was aimed to optimize and investigate the effect of formulation and process parameters for compounding poly (lactide-co-glycolide) PLGA thin film with plasticizer by hot melt extrusion (HME) process employing quality risk assessment and design of experiments (DoE).

Methods

Initial risk assessment studies were performed to identify the critical material attributes (CMAs) and critical process parameters (CPPs), affecting the critical quality attributes (CQAs) of the PLGA film. Different batches were prepared using the central composite face (CCF) design matrix with 5 factors at 2 levels and 3 central points, resulting a total of 29 experimental runs as per the design generated by the MODDE Pro software 11.0.1. The effect of critical variables over the product quality attributes was then evaluated by the analysis of variance (ANOVA) and multiple linear regression (MLR) analysis.

Results

Among the product quality attributes, only glass transition temperature (Tg) of PLGA film showed significant influence over the studied independent variables. R2 value was found to be 0.982, 0.962, and 0.923 for three responses, respectively, indicating the goodness of the model, and the validity of the model was proved by the close agreement between the experimentally observed values and predicted values. Further characterization studies of the optimized PLGA film by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and gel permeation chromatography (GPC) revealed no thermal or molecular modifications during the hot extrusion process.

Conclusions

A continuous and scalable HME method was successfully demonstrated using CCF design matrix for manufacturing PLGA polymer film which can be used as a biodegradable coating for medical device.

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Funding

The authors thankfully acknowledge the financial support received from Bill & Melinda Gates Foundation under the Grand Challenge Explorations [#OPP1025604] and HLL Lifecare Ltd, Trivandrum, Kerala, India-695012.

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Authors and Affiliations

  1. Corporate Research and Development Centre, HLL Lifecare Limited, Akkulam, Sreekariyam, Kerala, Trivandrum - 695017, India

    Midhu George Veeran, Resmy Rachel Thomas, Reshmi Ramakrishnan, Bharaniraja B & Abi Santhosh Aprem

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  1. Midhu George Veeran
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  2. Resmy Rachel Thomas
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Correspondence to Abi Santhosh Aprem.

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Veeran, M.G., Thomas, R.R., Ramakrishnan, R. et al. Quality-by-Design Approach for Optimization and Processing of PLGA Polymer Film by Hot Melt Extrusion. J Pharm Innov 17, 1282–1294 (2022). https://doi.org/10.1007/s12247-021-09600-2

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