How Does the CO2 in Supercritical State Affect the Properties of Drug-Polymer Systems, Dissolution Performance and Characteristics of Tablets Containing Bicalutamide?

Agata Antosik-Rogóż,Justyna Knapik-Kowalczuk,Joanna Szafraniec-Szczęsny,Karolina Gawlak,Mateusz Kurek,Marian Paluch,Renata Jachowicz,Vittorio P Danesi,Krzysztof Chmiel

doi:10.3390/ma13122848

Abstract

The increasing demand for novel drug formulations has caused the introduction of the supercritical fluid technology, CO2 in particular, into pharmaceutical technology as a method enabling the reduction of particle size and the formation of inclusion complexes and solid dispersions. In this paper, we describe the application of scCO2 in the preparation of binary systems containing poorly soluble antiandrogenic drug bicalutamide and polymeric excipients, either Macrogol 6000 or Poloxamer®407. The changes in the particle size and morphology were followed using scanning electron microscopy and laser diffraction measurements. Differential scanning calorimetry was applied to assess thermal properties, while X-ray powder diffractometry was used to determine the changes in the crystal structure of the systems. The dissolution of bicalutamide was also considered. Binary solid dispersions were further compressed, and the attributes of tablets were assessed. Tablets were analyzed directly after manufacturing and storage in climate chambers. The obtained results indicate that the use of supercritical CO2 led to the morphological changes of particles and the improvement of drug dissolution. The flowability of blends containing processed binary systems was poor; however, they were successfully compressed into tablets exhibiting enhanced drug release.

Highlights

The growing number of active pharmaceutical ingredients (APIs) are characterized by poor water solubility
We evaluated the use of the supercritical carbon dioxide method as a way to obtain solid dispersions with bicalutamide, which were further compressed into tablets
In the case of the particles of Poloxamer® 407, they were smooth and spherical, of a diameter varying between 50 μm and 250 μm (Figure 1C)

Summary

Introduction

The growing number of active pharmaceutical ingredients (APIs) are characterized by poor water solubility. The matrix can be made from low molecular weight compounds, or more frequently, hydrophilic polymers They provide the dissolution rate improvement, particle size reduction, reduction of agglomeration, wettability improvement that are achieved by solid dispersion [13,14]. They possess different functional groups, molecular weight, melting temperatures (Tm ), and glass transition temperatures (Tg ). They can be crystalline (poly(vinyl alcohol)), semicrystalline (poly L-lactic acid), or amorphous (polyvinylpyrrolidone)

Methods

Results

Conclusion