Hot Melt Extrusion in Engineering of Drug Cocrystals: A Review

Abstract

Crystal engineering technique has been widely explored in recent times to bring about changes in crystallinity which aids to achieve various goals such as solubility enhancement, stability and in vivo bioavailability without altering the chemical properties of the drug. Cocrystallisation is one of the crystal engineering approaches where the drug and an inert coformer are linked together by hydrogen bonding forming supramolecular homosynthon or heterosynthon using solvent-based or solvent-free techniques. Processing of active pharmaceutical ingredients with inert water-soluble coformers yields multicomponent crystalline cocrystals with high-performance characteristics and enhanced flow properties. Due to the emerging need of the industry for greener techniques, hot melt extrusion (HME), a continuous and solvent-free process is emerging as a field of interest in the mechanochemical synthesis of various pharmaceutical dosage forms such as solid dispersions, implants, ointments, and cocrystals. The current review emphasizes the role of HME as a cocrystallization technique for drugs to tailor-make their properties and ease of formulation. The distinct feature of HME is phase control during the process of cocrystallization. Furthermore, the selection of appropriate coformers with desirable water-solubility and stability features makes HME amenable to cocrystallization of versatile actives yielding suitable dosage forms. The application of process analytical technology further adds ease of monitoring during HME in cocrystallization approaches. Due to these salient features of HME, it can act as a prospective technique for cocrystallization of versatile drugs thus yielding dosage forms with desirable solubility and stability features.

Solid Dispersion as a Potential Approach to Improve Dissolution and Bioavailability of Curcumin From Turmeric (Curcuma Longa L.)

“…Critical process parameters that affect the characteristics of solid dispersion using the HME method include 1) temperature; an optimal temperature is needed to be able to change all crystalline forms to amorphous but still maintain drug stability; 2) the speed of the screw extruder, the slow speed of the screw extruder causes the drug contact time to be longer so it has the potential for degradation; 3) cooling method, amorphous solid dispersion can be produced by using the proper cooling method to avoid phase separation and drug nucleation [40,41].…”

Pharmaceutical cocrystal-a deft technique for solubility enhancement

“…These carrier systems are screened for their desirable features of stability and solubility. To achieve successful processing, the physical state, molecular weight of API, melting point, and polymer play an important role 29 . Fernandes et al utilized this method for the mechanochemical synthesis of carvedilol cocrystals 30 .…”

Bioavailability Enhancement Strategies for Rivaroxaban: A Noteworthy Review

“…Moreover, cocrystals can provide unique advantages over traditional drug delivery systems, such as improved drug targeting and reduced toxicity. With their ability to enhance drug performance, cocrystals offer tremendous potential for advancing drug delivery and efficacy in various therapeutic areas [20].…”