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Molecular pharmaceutics
Nov 04, 2024;21 (11): 5619-5631.

Computational Support to Explore Ternary Solid Dispersions of Challenging Drugs Using Coformer and Hydroxypropyl Cellulose.

Andreas Niederquell, Susanne Herzig, Monica Schönenberger, Edmont Stoyanov, Martin Kuentz
Author Information
  1. Andreas Niederquell: Institute for Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences FHNW, Hofackerstr. 30, 4132 Muttenz, Switzerland.
  2. Susanne Herzig: Institute for Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences FHNW, Hofackerstr. 30, 4132 Muttenz, Switzerland.
  3. Monica Schönenberger: Nano Imaging Lab, Swiss Nanoscience Institute, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
  4. Edmont Stoyanov: Nisso Chemical Europe, Berliner Allee 42, 40212 Düsseldorf, Germany.
  5. Martin Kuentz: Institute for Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences FHNW, Hofackerstr. 30, 4132 Muttenz, Switzerland. ORCID
PMID: 39388157 DOI: 10.1021/acs.molpharmaceut.4c00592

Abstract

A majority of drugs marketed in amorphous formulations have a good glass-forming ability, while compounds less stable in the amorphous state still pose a formulation challenge. This work explores ternary solid dispersions of two model drugs with a polymer (i.e., hydroxypropyl cellulose) and a coformer as stabilizing excipients. The aim was to introduce a computational approach by preselecting additives using solubility parameter intervals (i.e., overlap range of solubility parameter, ORSP) followed by more advanced COSMO-RS theory modeling. Thus, a mapping of calculated mixing enthalpy and melting points is proposed for evaluation prior to hot melt extrusion. Following experimental testing of process feasibility, the selected formulations were tested for their physical stability using conventional bulk analytics and by confocal laser scanning and atomic force microscopy imaging. In line with the screening, dl-malic and l-tartaric acid (20%, w/w) in HPC formulations showed no signs of early drug crystallization after 3 months. However, l-tartaric acid formulations displayed few crystals on the surface, which was likely a humidity-induced surface phenomenon. Although more research is needed, the conclusion is that the proposed computational small-scale extrusion approach of ternary solid dispersion has great potential in the formulation development of challenging drugs.

Keywords

coformer hot melt extrusion hydroxypropyl cellulose molecular interactions solid dispersion

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MeSH Term

Cellulose
Solubility
Excipients
Drug Compounding
Chemistry, Pharmaceutical
Crystallization
Drug Stability
Polymers
Computer Simulation
Hot Melt Extrusion Technology
Microscopy, Atomic Force

Chemicals

hydroxypropylcellulose
Cellulose
Excipients
Polymers
Journal Article
Article has an altmetric score of 5

Word Cloud

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