Opportunities and Challenges in Mechanochemical Cocrystallization toward Scaled-Up Pharmaceutical Manufacturing

Abstract

Recently, pharmaceutical cocrystals have gained immense interest because of their potential to tune mechanical, pharmacokinetic, and physicochemical properties of active pharmaceutical ingredients (APIs) while keeping their therapeutic action intact. In this review, cocrystallization is raised as a viable strategy toward commercialized pharmaceutical manufacturing, where attention has been paid to solid-state cocrystal preparation methods and their opportunities and challenges in overall product and process development. A comparative study of cocrystallization in the form of mechanical energy is demonstrated with the aid of SELECT criteria to qualitatively evaluate the synthetic route selection of scalable mechanochemical cocrystallization methods. Remedies and alternatives for the challenges that arise in mechanochemical synthesis of cocrystals are presented in this review, highlighting the commercial perspectives of sustainable, eco-friendly, and less toxic mechanochemical methods.

Mechanochemical Synthesis of Cocrystal: From Mechanism to Application

“…As an approach for rapid screening and green synthesis, mechanochemistry has enabled the development of an increasing number of cocrystals from the laboratory to the industrial scale. In contrast to published ones, ,,− this review highlights the pivotal role of mechanochemical synthesis of cocrystal. Notably, it not only delineates diverse mechanochemical strategies and formation mechanisms but also offers new insights into practical applications, including chiral resolution and mechanochemical-assisted single crystal resolution.…”

New Perspectives for Antihypertensive Sartans as Components of Co-crystals and Co-amorphous Solids with Improved Properties and Multipurpose Activity

“…In general, the most preferred apparatus used in the pharmaceutical industry is a thermostated mechanically stirred reactor . In turn, solid-state methods often require high mechanochemical forces and special equipment; however, problems related to purity of the obtained compounds are also encountered. , Of the previously mentioned methods for the synthesis of co-crystals and co-amorphous solid dispersions, only a few of them can be considered fully scalable . Methods that allow the production of co-crystals on an industrial scale include spray drying, , as well as spray congealing, which is a combination of spray drying and hot melt extrusion methods .…”

Solubility Enhancement of the Nonsteroidal Anti-inflammatory Drug of Pelubiprofen Salts

“…Majority of currently available orally acceptable prospective medications, active pharmaceutical ingredients (APIs), suffer from poor aqueous solubility, low permeability, slow dissolution rate, low bioavailability, and unstable formulations owing to a negative impact on therapeutic efficacy. − Thus, the design and manufacture of multicomponent solid forms (such as salt, cocrystal, and coamorphous forms) by supramolecular synthons and crystal engineering are achieved. Among the various multicomponent solid forms, the salt and cocrystal formations are particularly appealing for enhancing drug solubility and dissolution rate and modify the physicochemical and pharmacological behaviors of the drugs. − Such multicomponent solid formations primarily rely on supramolecular alteration as a result of the molecular arrangement in the crystal lattice and noncovalent intermolecular interactions due to hydrogen bonding, dipole–dipole, ion–ion, ion-dipole, and halogen bonding, − hygroscopicity, compaction behavior, chemical and physical stability as well as flow-, tablet-, and bioavailability, inevitably depicting their phenomenal wide range abilities. − In these salt and cocrystal formations, the choice of GRAS (generally regarded as safe) coformer is crucial for improving the physicochemical property of drug. − …”