Co-Amorphous Drug Formulations in Numbers: Recent Advances in Co-Amorphous Drug Formulations with Focus on Co-Formability, Molar Ratio, Preparation Methods, Physical Stability, In Vitro and In Vivo Performance, and New Formulation Strategies

Abstract

Co-amorphous drug delivery systems (CAMS) are characterized by the combination of two or more (initially crystalline) low molecular weight components that form a homogeneous single-phase amorphous system. Over the past decades, CAMS have been widely investigated as a promising approach to address the challenge of low water solubility of many active pharmaceutical ingredients. Most of the studies on CAMS were performed on a case-by-case basis, and only a few systematic studies are available. A quantitative analysis of the literature on CAMS under certain aspects highlights not only which aspects have been of great interest, but also which future developments are necessary to expand this research field. This review provides a comprehensive updated overview on the current published work on CAMS using a quantitative approach, focusing on three critical quality attributes of CAMS, i.e., co-formability, physical stability, and dissolution performance. Specifically, co-formability, molar ratio of drug and co-former, preparation methods, physical stability, and in vitro and in vivo performance were covered. For each aspect, a quantitative assessment on the current status was performed, allowing both recent advances and remaining research gaps to be identified. Furthermore, novel research aspects such as the design of ternary CAMS are discussed.

BX795-Organic Acid Coevaporates: Evaluation of Solid-State Characteristics, In Vitro Cytocompatibility and In Vitro Activity against HSV-1 and HSV-2

“…The development of co-amorphous systems is an emerging amorphization strategy to improve the physicochemical and biopharmaceutical properties of the drug. The co-amorphous systems involve combining drug and low molecular weight organic excipient (the co-former) in an equimolar ratio using suitable methods to yield a homogenous amorphous single phase [27][28][29]. It should be noted that several studies have established the ability of citric acid and tartaric acid to form co-amorphous systems with weakly basic drugs [30][31][32][33], which corroborates our results on the formation of BX795-tartaric acid/citric acid co-amorphous systems.…”

Amorphous Form of Carvedilol Phosphate—The Case of Divergent Properties

“…Due to the long path and high cost of discovering and developing new therapeutic molecules, the trend is observed to improve the physicochemical properties of API with a known profile of action [ 10 , 11 ]. In drugs belonging to the 2 BCS group, the research aims to improve solubility, thus increasing bioavailability.…”

New Insights on Solvent Implications in the Design of Materials Based on Cellulose Derivatives Using Experimental and Theoretical Approaches

“…In recent years, a great interest was given to the research on the design of new polymeric materials with adapted properties and multiple functionalities, from technology to biomedical and environmental applications [1][2][3]. In this context, the physical mixing of two polymers or more represents simplest conceptual way to achieve the desired properties of new materials.…”

“…Nowadays, cellulose derivatives gained substantial consideration, due to their specific properties, e.g., biodegradability, biocompatibility, nontoxicity, solubility in water, etc., having large applicability in the chemical industries, biomedical, pharmaceutical, cosmetics, water desalination [1,2,21,22], as an effect of special viscometric behavior in solution. Particular properties of these derivatives can be optimized by utilization of polymer blends principle, which permits attaining of new models of materials, with a wide range of qualities [23].…”

“…Besides, the use of water as a solvent for HPMC and PVP can influence their flow behavior, and hence, the finite product performance [27]. Taking into account all the above, in the present study, (hydroxypropyl)methyl cellulose and poly(vinylpyrrolidone) were selected due to their excellent physical properties, including their solubility in water, absence of toxicity, high hydrophilicity, flexibility, film-forming, and outstanding chemical and thermal stabilities [1][2][3]15,18,21,23,28]. Based on such versatile properties, an extensive attention was accorded to the use of both polymers as multifunctional materials for a variety of applications.…”