Luiza Orszulak, Patryk Włodarczyk, Barbara Hachuła, Taoufik Lamrani, Karolina Jurkiewicz, Magdalena Tarnacka, Marek Hreczka, Kamil Kamiński, Ewa Kamińska
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引用次数: 0
Abstract
This paper presents an innovative approach that utilizes self-synthesized homopolymers of polyvinylpyrrolidone (PVP) with different architectures as effective matrices for inhibiting the crystallization of naproxen (NAP). We have thoroughly investigated amorphous solid dispersions containing NAP and (i) self-synthesized linear PVP, (ii) self-synthesized three-armed star-shaped PVP, and (iii) self-synthesized linear PVP with a mass (Mn) corresponding to the length of one arm of the star polymer, as well as (iv) commercial linear PVP K30 as a reference. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and infrared spectroscopy (FTIR) studies, as well as molecular dynamics simulations were conducted to gain comprehensive insights into the thermal and structural properties, as well as intermolecular interactions in the NAP-PVP systems. The main purpose of all experiments was to assess the impact of macromolecule structure (topology, molecular weight) on the kinetics of the crystallization of NAP - a drug that is very difficult to vitrify. Our studies clearly showed that the most effective matrix in inhibiting the NAP crystallization is linear, self-synthesized PVP with higher molecular weight (Mn) similar to that of the commercial PVP K30, but lower, strictly controlled dispersity. We also found that crystallization of API proceeds at a similar pace for the binary mixture composed of a star-shaped PVP and linear polymer with Mn corresponding to Mn of one arm of the star-shaped macromolecule in the vicinity of the Tg. The obtained data highlight the key role of polymer structure in designing new pharmaceutical formulations.
期刊介绍:
The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics.
Topics covered include for example:
Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids)
Aspects of manufacturing process design
Biomedical aspects of drug product design
Strategies and formulations for controlled drug transport across biological barriers
Physicochemical aspects of drug product development
Novel excipients for drug product design
Drug delivery and controlled release systems for systemic and local applications
Nanomaterials for therapeutic and diagnostic purposes
Advanced therapy medicinal products
Medical devices supporting a distinct pharmacological effect.