Use of supercritical CO₂‐aided and conventional melt extrusion for enhancing the dissolution rate of an active pharmaceutical ingredient

Abstract

Dispersing at the molecular level a drug in a polymer matrix is a major challenge to be addressed by the pharmaceutical industry to enhance its bioavailability or to control its release. Melt extrusion and supercritical CO 2 -aided melt extrusion of solid pharmaceutical formulations were performed to enhance the dissolution rate of carvedilol, taken as a model of poorly soluble drug. The presence of the drug improved the processability of the polyacrylate matrix (Eudragit E) through its plasticizing effect. The supercritical method was found gentle compared with melt extrusion owing to the shorter residence time and lower processing temperature and melt viscosity. No traces of decomposition of the drug could be detected after the supercritical extrusion process based on capillary electrophoresis results. This extrusion process resulted in effective homogenization of the components and amorphization of the drug according to Raman mapping, Fourier transform infrared spectrometry, X-ray diffraction, and polarized light microscopy. The kinetics of dissolution can be dramatically improved. C

Comparison of Electrospun and Extruded Soluplus®-Based Solid Dosage Forms of Improved Dissolution

“…High standard deviation (SD ∼10%–19%) and range between the minimum and maximum values (range ∼54%–78%) clearly demonstrate the inhomogeneous distribution of spironolactone in the physical mixtures. These representative values are considerably lower in the case of the extrudates (SD ∼2%–3%, range ∼24%–28%), which indicate relatively homogeneous distribution of spironolactone compared with prior published12 relevant results and the visualized Raman maps prove the same. Distribution of spironolactone in the electrospun fibers is extremely homogeneous based on the visualized Raman maps and the statistical data (SD ∼0.5%–0.7%, range ∼5%–7%).…”

“…In recent years, different types of melt extrusion methods (conventional,8,9 supercritical,10 – 12 and lipid13,14) have been developed to increase or control the release of the APIs. The technology and applications have been thoroughly reviewed by Breitenbach15 and Lakshman et al16 These researches clearly showed the capability of melt extrusion to tackle the challenge of dissolution in several cases.…”

Plasticized Drug‐Loaded Melt Electrospun Polymer Mats: Characterization, Thermal Degradation, and Release Kinetics

“…a) from Sigma–Aldrich (Budapest, Hungary) with purity ≥99% was used as API. The melting point of CAR is 117°C . Eudragit® E PO (EPO; Fig.…”

“…There are diverse methods to prepare drug‐loaded solid dispersions using polymers and other excipients meeting the requirements of the pharmaceutical industry . One of these methods is the melt extrusion, a solvent‐free continuous tool for dispersing API in a polymeric matrix, thereby improving its dissolution . The pharmaceutical viability of melt extrusion is proven by marketed products (Kaletra, Isoptin SR‐E) as well …”

Capillary rheometry of a binary mixture polymer/CO2 in a single screw extruder

“…Thus, this may allow the use of fragile or thermolabile molecules, like active pharmaceutical ingredients. Furthermore, the absence of residues in the final material is also an advantage for pharmaceutical applications [6,7].…”