Surface stabilization and dissolution rate improvement of amorphous compacts with thin polymer coatings: can we have it all?

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Novakovic , D , Peltonen , L , Isomäki , A O , Fraser-Miller , S J , Hagner Nielsen , L , Laaksonen , T & Strachan , C 2020 , ' Surface stabilization and dissolution rate improvement of amorphous compacts with thin polymer coatings: can we have it all? ' , Molecular Pharmaceutics , vol. 17 , no. 4 , pp. 1248-1260 . https://doi.org/10.1021/acs.molpharmaceut.9b01263

Title: Surface stabilization and dissolution rate improvement of amorphous compacts with thin polymer coatings: can we have it all?
Author: Novakovic, Dunja; Peltonen, Leena; Isomäki, Antti Olavi; Fraser-Miller, Sara J.; Hagner Nielsen, Line; Laaksonen, Timo; Strachan, Clare
Contributor: University of Helsinki, Division of Pharmaceutical Chemistry and Technology
University of Helsinki, Drug Research Program
University of Helsinki, Department of Anatomy
University of Helsinki, Tampere University of Technology
University of Helsinki, Drug Research Program
Date: 2020-04-06
Language: eng
Number of pages: 13
Belongs to series: Molecular Pharmaceutics
ISSN: 1543-8384
URI: http://hdl.handle.net/10138/314643
Abstract: The distinction between surface and bulk crystallization of amorphous pharmaceuticals, as well as the importance of surface crystallization for pharmaceutical performance, is becoming increasingly evident. An emerging strategy in stabilizing the amorphous drug form is to utilize thin coatings at the surface. While the physical stability of systems coated with pharmaceutical polymers has recently been studied, the effect on dissolution performance as a function of storage time, as a further necessary step toward the success of these formulations, has not been previously studied. Furthermore, the effect of coating thickness has not been elucidated. This study investigated the effect of these polymer-coating parameters on the interplay between amorphous surface crystallization and drug dissolution for the first time. The study utilized simple tablet-like coated dosage forms, comprising a continuous amorphous drug core and thin polymer coating (hundreds of nanometers to a micrometer thick). Monitoring included analysis of both the solid-state of the model drug (with SEM, XRD, and ATR FTIR spectroscopy) and dissolution performance (and associated morphology and solid-state changes) after different storage times. Stabilization of the amorphous form (dependent on the coating thickness) and maintenance of early-stage intrinsic dissolution rates characteristic for the unaged amorphous drug were achieved. However, dissolution in the latter stages was likely inhibited by the presence of a polymer at the surface. Overall, this study introduced a versatile coated system for studying the dissolution of thin-coated amorphous dosage forms suitable for different drugs and coating agents. It demonstrated the importance of multiple factors that need to be taken into consideration when aiming to achieve both physical stability and improved release during the shelf life of amorphous formulations.
Subject: CRYSTAL-GROWTH
DIFFUSION
FORMULATIONS
GLASS-TRANSITION TEMPERATURE
INDOMETHACIN CRYSTALLIZATION
INHIBITION
MOBILITY
MOLECULAR GLASSES
PHYSICAL STABILITY
POLY(VINYLPYRROLIDONE)
amorphous
dissolution
indomethacin
polymer coating
surface crystallization
317 Pharmacy
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