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  • Title: Complex amorphous solid dispersions based on poly(2-hydroxyethyl methacrylate): Study of drug release from a hydrophilic insoluble polymeric carrier in the presence and absence of a porosity increasing agent.
    Author: Everaerts M, Van den Mooter G.
    Journal: Int J Pharm; 2019 Jul 20; 566():77-88. PubMed ID: 31103819.
    Abstract:
    Amorphous solid dispersions are nowadays typically made up of a drug compound and a water-soluble polymer. However, recently it has been demonstrated that amorphous solid dispersions based on insoluble polymers have a different and more delayed drug release profile, resulting in a prolonged duration of supersaturation. In this paper, binary and ternary amorphous solid dispersions based on poly(2-hydroxyethyl methacrylate) were prepared through spray drying to further investigate the potential of this type of carrier. As drug release from this matrix system was expected to be dictated by a diffusion-driven process, porosity of the formulation was adjusted by the inclusion of a water-soluble polymer. The solid state of the formulations was characterized with modulated differential scanning calorimetry, X-ray powder diffraction and thermogravimetric analysis. The release of drug and of the porosity increasing agent was measured in acidic and neutral conditions. In addition, the release performance of the spray dried product was compared with the drug release from poly(2-hydroxyethyl methacrylate) beads, which had already been reported in literature. It appeared that in the case of the spray dried poly(2-hydroxyethyl methacrylate), drug and porosity increasing agent could only be released to a certain extent due to entrapment of both compounds in the poly(2-hydroxyethyl methacrylate) network. While the chemical crosslinks of poly(2-hydroxyethyl methacrylate) beads ensured a more rigid structure with sufficient free space for drug diffusion, the spray dried product was susceptible to intense physical crosslinking upon contact with the dissolution medium.
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