Low Molecular Weight Oligomers of Poly(alkylene succinate) Polyesters as Plasticizers in Poly(vinyl alcohol) Based Pharmaceutical Applications.

Artemis Palamidi,Dimitrios N Bikiaris,Afroditi Kapourani,Panagiotis Barmpalexis,Konstantinos N Kontogiannopoulos,Apostolos Kyritsis,Panagiotis A Klonos,Evi Christodoulou

doi:10.3390/polym13010146

Artemis Palamidi, Dimitrios N Bikiaris + Show 6 more

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https://doi.org/10.3390/polym13010146

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Abstract

The plasticizing effect of three low molecular weight oligomers of aliphatic poly(alkylene succinate) polyesters, namely poly(butylene succinate) (PBSu), poly(ethylene succinate) (PESu), and poly(propylene succinate) (PPSu), on partially hydrolyzed poly(vinyl alcohol) (PVA) used in melt-based pharmaceutical applications, was evaluated for the first time. Initially, the three aliphatic polyesters were prepared by the melt polycondensation process and characterized by differential scanning calorimetry (DSC), 1H NMR, intrinsic viscosity, and size exclusion chromatography (SEC). Subsequently, their effect on the thermophysical and physicochemical properties of PVA was thoroughly evaluated. According to the obtained results, PVA was completely miscible with all three polyesters, while PESu induced PVA’s thermal degradation, with the phenomenon starting from ~220 °C, in contrast to PBSu and PPSu, where a thermal profile similar to PVA was observed. Furthermore, molecular interactions between PVA and the prepared poly(alkylene succinate) polyesters were revealed by DSC, ATR-FTIR, and molecular dynamics simulations. Finally, melt flow index (MFI) measurements showed that, in contrast to PBSu, the use of PESu or PPSu significantly improved PVA’s melt flow properties. Hence, according to findings of the present work, only the use of low molecular weight PPSu is suitable in order to reduce processing temperature of PVA and improve its melt flow properties (plasticizing ability) without affecting its thermal decomposition.

Highlights

IntroductionThe poor aqueous solubility (and the restricted bioavailability) of the newly developed Active Pharmaceutical Ingredients (APIs) has been a major obstacle for the development of efficient drug formulations
The poor aqueous solubility of the newly developed Active Pharmaceutical Ingredients (APIs) has been a major obstacle for the development of efficient drug formulations
In the case of PPSu, there was a single peak at 2.63 ppm attributed to methylene protons of succinic acid, a, a triple peak at 4.09–4.21 ppm attributed to c protons and a multiple peak between 1.9 and 2.02 ppm corresponding to d protons

Summary

Introduction

The poor aqueous solubility (and the restricted bioavailability) of the newly developed Active Pharmaceutical Ingredients (APIs) has been a major obstacle for the development of efficient drug formulations. Amorphous solid dispersions (ASDs) were proved to be one of the most promising techniques to increase the apparent solubility and dissolution of APIs, and their therapeutic effect [5]. Several different approaches have been proposed for the manufacturing of ASDs, which can be categorized into two general classes: the solvent-based methods and the fusion-based methods [8]. Fusion or melt -based methods such as hot-melt extrusion and melt mixing, have gained increased attention and are widely selected in the pharmaceutical arena, as they offer several advantages such as shorter time to achieve the final product and the elimination of solvent use [9–11]

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