Enhanced Dissolution of a Porous Carrier–Containing Ternary Amorphous Solid Dispersion System Prepared by a Hot Melt Method

Abstract

The focus of our study was to employ a solvent-free, thermal process to evaluate the use of a porous carrier in a drug-polymer-porous carrier ternary formulation containing a high drug load (e.g., ≥50% w/w). The purpose of the study was to improve the dissolution properties of the biopharmaceutical classification system class II drug, indomethacin, in the ternary formulation. The effect that the selected polymer has on properties of the formulation was studied, and the formulation characteristics of hypromellose (AF15), copovidone (VA64), and polyvinyl alcohol-polyethylene glycol graft copolymer was evaluated to understand differences in dissolution rates and drug adsorption onto the porous carrier. The ternary formulations were manufactured using a thermal technique that relied on heating and mixing, without the necessity of mechanical shear. All thermally processed granules that employed the porous carrier exhibited immediate release compared with crystalline indomethacin and physical mixtures. In addition, the ternary formulations maintained supersaturation compared with the binary formulations without polymer. The results of this study indicated that the thermally processed ternary formulations containing a porous carrier demonstrated a much improved dissolution profile in nonsink conditions.

Understanding the Role of Sodium Lauryl Sulfate on the Biorelevant Solubility of a Combination of Poorly Water-Soluble Drugs Using High Throughput Experimentation and Mechanistic Absorption Modeling

“…However, researchers from pharmaceutical industry and academia have found and implemented innovative solutions and technologies to manage the challenge. These approaches include particle size reduction (7,8), salt screening (9), co-crystal formation (10), polymer complexation (11), prodrug formation (12), micellization (13), solid dispersions (14)(15)(16)(17)(18), self- (19,20), supercritical fluid (SCF) technology (21), and surfactant systems (to improve wettability) (22,23).…”

Novel in vitro and in silico tools for the development of mesoporous silica formulations with optimal precipitation inhibitors

“…Encouragingly, the inclusion of HPMCAS in this process did not have an impact on the ability of the drug to enter the pores, in line with earlier findings in which HPMCAS was successfully co-incorporated during the loading of celecoxib onto mesoporous silica without any impact on the final solid-state form of the formulation (Laine et al 2016). This work paralleled attempts at incorporating mesoporous silica in HME platforms, in which Hanada and co-workers demonstrated that silica could be successfully utilized alongside HPMC to yield a high drug-load, ternary drug-silica-polymer system (Hanada et al 2018). One significant difference, however, was the appearance of the particles when HPMCAS was incorporated during the loading process.…”

Fundamental Aspects of a Third Component Used in Ternary Solid Dispersion: A Review

“…Adding a third component (ternary agent) to produce a TSD system gives improved stability, greater miscibility, stronger intermolecular interactions, significantly higher water-solubility, and synergistic benefit in all of these factors compared to the BSDs [31]. The carrier used in combination with a ternary agent could be a polymer, surfactant or a polymer with surfactant property [32,33]. Examples of ternary agents comprise surfactant [34], polymer [35], adsorbent [36], pH modulator [37] and hydrotropic agent [38].…”