Stability-enhanced Hot-melt Extruded Amorphous Solid Dispersions via Combinations of Soluplus® and HPMCAS-HF
Journal Title: AAPS PharmSciTech - Year 2015, Vol 16, Issue 4
Abstract
The aim of this study was to evaluate a novel combination of Soluplus® and hypromellose acetate succinate (HPMCAS-HF) polymers for solubility enhancement as well as enhanced physicochemical stability of the produced amorphous solid dispersions. This was accomplished by converting the poorly water-soluble crystalline form of carbamazepine into a more soluble amorphous form within the polymeric blends. Carbamazepine (CBZ), a Biopharmaceutics Classification System class II active pharmaceutical ingredient (API) with multiple polymorphs, was utilized as a model drug. Hot-melt extrusion (HME) processing was used to prepare solid dispersions utilizing blends of polymers. Drug loading showed a significant effect on the dissolution rate of CBZ in all of the tested ratios of Soluplus® and HPMCAS-HF. CBZ was completely miscible in the polymeric blends of Soluplus® and HPMCAS-HF up to 40% drug loading. The extrudates were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and dissolution studies. DSC and XRD data confirmed the formation of amorphous solid dispersions of CBZ in the polymeric blends of Soluplus® and HPMCAS-HF. Drug loading and release of CBZ was increased with Soluplus® (when used as the primary matrix polymer) when formulations contained Soluplus® with 7–21% (w/w) HPMCAS-HF. In addition, this blend of polymers was found to be physically and chemically stable at 40°C, 75% RH over 12 months without any dissolution rate changes.
Authors and Affiliations
Saad M. Alshahrani, Wenli Lu, Jun-Bom Park, Joseph T. Morott, Bader B. Alsulays, Soumyajit Majumdar, Nigel Langley, Karl Kolter, Andreas Gryczke, Michael A. Repka
Keywords
Related Articles
- EP ID EP682251
- DOI 10.1208/s12249-014-0269-6
- Views 49
- Downloads 0
Microscopic Modeling of País Grape Seed Extract Absorption in the Small Intestine
The concentration profiles and the absorbed fraction (F) of the País grape seed extract in the human small intestine were obtained using a microscopic model simulation that accounts for the extracts' dissolution...
Drying Using Supercritical Fluid Technology as a Potential Method for Preparation of Chitosan Aerogel Microparticles
Supercritical fluid technology offers several advantages in preparation of microparticles. These include uniformity in particle size, morphology, and drug distribution without degradation of the product. One of the recen...
Kinetic Modelling for the Assay of Nortriptyline Hydrochloride Using Potassium Permanganate as Oxidant
Kinetic methods for accurate determination of nortriptyline hydrochloride have been described. The methods are based on the oxidation of nortriptyline hydrochloride with KMnO4 in acidic and basic media. In acidic medium,...
The Stabilization of Amorphous Zopiclone in an Amorphous Solid Dispersion
Zopiclone is a poorly soluble psychotherapeutic agent. The aim of this study was to prepare and characterize an amorphous form of zopiclone as well as the characterization and performance of a stable amorphous solid disp...
A Prospective Analysis of Co-Processed Non-Ionic Surfactants in Enhancing Permeability of a Model Hydrophilic Drug
Paracellular route is a natural pathway for the transport of many hydrophilic drugs and macromolecules. The purpose of this study was to prospectively evaluate the ability of novel co-processed non-ionic surfactants to e...