Hot Melt Extrusion: an Emerging Green Technique for the Synthesis of High-Quality Pharmaceutical Cocrystals
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REVIEW ARTICLE
Hot Melt Extrusion: an Emerging Green Technique for the Synthesis of High-Quality Pharmaceutical Cocrystals Prabhakar S. Panzade 1,2
&
Giridhar R. Shendarkar 1 & Deepak A. Kulkarni 2
Accepted: 26 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Hot melt extrusion (HME) is emerging as a continuous, single-step, scalable, and industrially feasible process for the production of cocrystals. HME has gained momentum as a continuous and solvent-free process in the manufacturing of cocrystals. The incorporation of the matrix and the use of process analytical tool (PAT) for real-time monitoring further facilitate the process. The advantages and disadvantages of various cocrystal production methods including HME process are provided in the manuscript. Besides, an overview of the HME process and equipment, critical process parameters, and PAT for real-time monitoring of process has been reviewed in this article. Finally, recent literature related to the cocrystal synthesis via HME has been presented critically. This review provides useful information for the synthesis of the cocrystals using HME process. Keywords Hot melt extrusion . Pharmaceutical cocrystal . Process analytical tool . Solvent-free method . Applications
Introduction Over the two decades, cocrystallization of active pharmaceutical ingredients (APIs) acquired a remarkable increase. Cocrystals are “multi-component crystalline solids that are neutral homogeneous molecular and/or ionic compounds generally in a stoichiometric ratio, which are neither solvates nor simple salts” [1–3]. Cocrystal composed of the same coformer may exist in distinct stoichiometric configuration [4–6]. The formation of supramolecular homosynthon (e.g., carboxylic acid-carboxylic acid) or supramolecular heterosynthon (e.g., carboxylic acid-amide) approach is used in the design of cocrystals. Nevertheless, supramolecular heterosynthon is the prevalent strategy due to promising interaction between unlike molecules which frequently results in H-bonding and thermodynamically stable cocrystals [2, 7, 8]. The general process depicting the cocrystal product development is demonstrated in Fig. 1.
* Prabhakar S. Panzade [email protected] 1
Center for Research in Pharmaceutical Sciences, Nanded Pharmacy College, Sham Nagar, Nanded, India
2
Department of Pharmaceutics, Srinath College of Pharmacy, Waluj, Aurangabad, India
The enhancement of physical property is of a special concern to the pharmaceuticals as the mainstreams of medicines are delivered in solid forms [5, 9, 10]. Physical properties of the solids in pharmaceutical drug product directly affect the processing, delivery, and, eventually, functioning of the drug product [11, 12]. Conversely, a cocrystal has altered physicochemical, mechanical, and biological properties including intrinsic solubility, dissolution rate, hygroscopicity, melting point, compressibility, and bioavailability [13–15]. This is due to the different crystal structures of a cocrystal than eith
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