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Influence of Plasdone™ S630 Ultra—an Improved Copovidone on the Processability and Oxidative Degradation of Quetiapine Fumarate Amorphous Solid Dispersions Prepared via Hot-Melt Extrusion Technique

  • Research Article
  • Theme: Amorphous Binary and Ternary Solid Dispersions: Recent Innovations and Advancements
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Abstract

In a formulation, traces of peroxides in copovidone can impact the stability of drug substances that are prone to oxidation. The present study aimed to investigate the impact of peroxides in novel Plasdone™ S630 Ultra and compare it with regular Plasdone™ S630 on the oxidative degradation of quetiapine fumarate amorphous solid dispersions prepared via hot-melt extrusion technique. The miscibility of copovidones with drug was determined using the Hansen solubility parameter, and the results indicated a miscible drug–polymer system. Melt viscosity as a function of temperature was determined for the drug–polymer physical mixture to identify the suitable hot-melt extrusion processing temperature. The binary drug and polymer (30:70 weight ratio) amorphous solid dispersions were prepared at a processing temperature of 160°C. Differential scanning calorimetry and Fourier transform infrared spectroscopy studies of amorphous solid dispersions revealed the formation of a single-phase amorphous system with intermolecular hydrogen bonding between the drug and polymer. The milled extrudates were compressed into tablets by using extragranular components and evaluated for tabletability. Stability studies of the milled extrudates and tablet formulations were performed to monitor the oxidative degradation impurity (N-oxide). The N-oxide impurity levels in the quetiapine fumarate - Plasdone™ S630 Ultra milled extrudates and tablet formulations were reduced by 2- and 3-folds, respectively, compared to those in quetiapine fumarate - Plasdone™ S630. The reduced oxidative degradation and improved hot-melt extrusion processability of Plasdone™ S630 Ultra make it a better choice for oxidation-labile drugs over Plasdone™ S630 copovidone.

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Funding

This work was partially supported by the National Institute of General Medical Sciences (NIGMS), a component of the National Institutes of Health (NIH) as one of its Centers of Biomedical Research Excellence (COBRE), under Grant Number P30GM122733-01A1.

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Authors and Affiliations

  1. Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Oxford, Mississippi, 38677, USA

    Arun Butreddy, Sandeep Sarabu, Suresh Bandari & Michael A. Repka

  2. Ashland Specialty Ingredients, Wilmington, Delaware, 19808, USA

    Amol Batra, Kamaru Lawal, Nick Ningyi Chen, Vivian Bi & Thomas Durig

  3. Pii Center for Pharmaceutical Technology, The University of Mississippi, University, Oxford, Mississippi, 38677, USA

    Michael A. Repka

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  1. Arun Butreddy
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  2. Sandeep Sarabu
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Correspondence to Michael A. Repka.

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Butreddy, A., Sarabu, S., Bandari, S. et al. Influence of Plasdone™ S630 Ultra—an Improved Copovidone on the Processability and Oxidative Degradation of Quetiapine Fumarate Amorphous Solid Dispersions Prepared via Hot-Melt Extrusion Technique. AAPS PharmSciTech 22, 196 (2021). https://doi.org/10.1208/s12249-021-02069-9

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