Mefenamic Acid – HPMC AS HG Amorphous Solid Dispersions: Dissolution Enhancement Using Hot Melt Extrusion Technology
Mefenamic acid, a BCS class II drug, displays high permeability and low solubility, thereby exhibiting a poor dissolution profile. Hence to improve the solubility and dissolution rate of Mefenamic acid, Hot Melt Extrusion (HME) technique was employed. The amorphous solid dispersion matrix exhibited enhanced dissolution with desired release characteristics. Hydroxypropylmethylcellulose acetate succinate (AquaSolve™ HPMC-AS HG) was used as a carrier with the poloxamer (Kolliphor P407).
The drug load was varied from 20% to 40% within the blend. Drug and polymers were blended using a twin shell V-blender for 10 minutes and extruded using an 11mm twin-screw co-rotating extruder (ThermoFisher Scientific, Waltham, MA, USA). The processing conditions were selected by conducting pre-formulation studies, which included thermogravimetric analysis (TGA) to determine the thermal degradation temperature of mefenamic acid and selected polymers. Differential Scanning Calorimetry (DSC) was performed to determine the Tg of the polymers and Tm of the API.
The extruded strands were collected, milled and sifted through a #30 sieve. This milled and sieved product was then subjected to DSC to characterize the state of drug in solid dispersions. The drug content of the extrudates was observed to be in acceptable range. To assess the drug release profile of the extrudates, in vitro dissolution testing was conducted in pH 7.4, phosphate buffer. Scanning Electron Microscopy was performed to study the morphology of the solid dispersions and Fourier Transform Infrared Spectroscopy was also performed to make sure that the drug and polymers are compatible with each other.
Formulations containing Kolliphor P407 exhibited enhanced dissolution profiles compared to the pure Mefenamic acid and solid dispersions with plain HPMC-AS HG. The DSC results illustrated the amorphous conversion of Mefenamic acid in the solid dispersions. The stability studies indicated that the optimized formulation with 20% drug load was found to be stable and in amorphous form with similar release profile after 3 months of study. Solid dispersions of Mefenamic acid with improved dissolution rate were prepared using Hot Melt Extrusion technology.
See the article
Shukla, Ashay, “Mefenamic Acid – HPMC AS HG Amorphous Solid Dispersions: Dissolution Enhancement Using Hot Melt Extrusion Technology” (2019). Electronic Theses and Dissertations. 1690.
https://egrove.olemiss.edu/etd/1690