The influence of drug and polymer particle size on the in situ amorphization using microwave irradiation

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In this study, the impact of drug and polymer particle size on the in situ amorphization using microwave irradiation at a frequency of 2.45 GHz were investigated. Using ball milling and sieve fractioning, the crystalline drug celecoxib (CCX) and the polymer polyvinylpyrrolidone (PVP) were divided into two particle size fractions, i.e. small (<71 µm) ( and large>71 µm) particles. Subsequently, compacts containing a drug load of 30% (w/w) crystalline CCX in PVP were prepared and subjected to microwave radiation for an accumulated duration of 600 sec in intervals of 60 sec as well as continuously for 600 sec. It was found that the compacts containing small CCX particles displayed faster rates of amorphization and a higher degree of amorphization during microwave irradiation as compared to the compacts containing large CCX particles. For compacts with small CCX particles, interval exposure to microwave radiation resulted in a maximum degree of amorphization of 24%, whilst a fully amorphous solid dispersion (100%) was achieved after 600 sec of continuous exposure to microwave radiation. By monitoring the temperature in the core of the compacts during exposure to microwave radiation using a fiber optic temperature probe, it was found that the total exposure time above the glass transition temperature (Tg) was shorter for the interval exposure method compared to continuous exposure to microwave radiation. Therefore, it is proposed that the in situ formation of an amorphous solid dispersion is governed by the dissolution of drug into the polymer, which most likely is accelerated above the Tg of the compacts. Hence, prolonging the exposure time above the Tg, and increasing the surface area of the drug by particle size reduction will increase the dissolution rate and thus, rate and degree of amorphization of CCX during exposure to microwave radiation.

Original languageEnglish
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume149
Pages (from-to)77-84
Number of pages8
ISSN0939-6411
DOIs
Publication statusPublished - Apr 2020

    Research areas

  • Amorphous solid dispersion, Dissolution, Glass solution, In situ amorphization, Microwave irradiation, Particle size, Temperature, Transmission Raman spectroscopy

ID: 236717235