Compaction Behavior of Co-Amorphous Systems

Abstract

Co-amorphous systems have been shown to be a promising strategy to address the poor water solubility of many drug candidates. However, little is known about the effect of downstream processing-induced stress on these systems. The aim of this study is to investigate the compaction properties of co-amorphous materials and their solid-state stability upon compaction. Model systems of co-amorphous materials consisting of carvedilol and the two co-formers aspartic acid and tryptophan were produced via spray drying. The solid state of matter was characterized using XRPD, DSC, and SEM. Co-amorphous tablets were produced with a compaction simulator, using varying amounts of MCC in the range of 24 to 95.5% (w/w) as a filler, and showed high compressibility. Higher contents of co-amorphous material led to an increase in the disintegration time; however, the tensile strength remained rather constant at around 3.8 MPa. No indication of recrystallization of the co-amorphous systems was observed. This study found that co-amorphous systems are able to deform plastically under pressure and form mechanically stable tablets.

Preparation and Characterization of a Rifampicin Coamorphous Material with Tromethamine Coformer: An Experimental–Theoretical Study

“…For RIF, dehydration is shown at lower temperatures, followed by melting at 176. 6 °C and decomposition at 194.6 °C. 12 The TRIS thermogram shows the solid−solid phase transition (α-orthorhombic to γcubic-body-centered) at 132.9 °C and the melting point at 168.8 °C.…”

“…4 Coamorphous systems are defined as multicomponent single-phase amorphous generally composed by a combination of an API and a low-molecular-weight molecule. 5,6 These systems are more stable than an amorphous material due to the main interactions from hydrogen bonds, van der Waals, and π interactions between the drug and the coformer. 7−9 The choice of coformers is made according to the characteristics of the desired product, as well as the type of functional groups present in the API.…”

“…Coamorphous systems appear as an alternative to increase the stability of the amorphous form without hindering its solubility but instead improving it . Coamorphous systems are defined as multicomponent single-phase amorphous generally composed by a combination of an API and a low-molecular-weight molecule. , These systems are more stable than an amorphous material due to the main interactions from hydrogen bonds, van der Waals, and π interactions between the drug and the coformer. − The choice of coformers is made according to the characteristics of the desired product, as well as the type of functional groups present in the API. , Thus, using coamorphous systems, it is possible to improve physicochemical properties such as water solubility, resulting in an increase in its dissolution rate, bioavailability, and, consequently, therapeutic efficacy …”

“…10,11 Thus, using coamorphous systems, it is possible to improve physicochemical properties such as water solubility, resulting in an increase in its dissolution rate, bioavailability, and, consequently, therapeutic efficacy. 6 Rifampicin (RIF) is a drug with low aqueous solubility and high membrane permeability, and it belongs to Class II of the Biopharmaceutical Classification System (BCS). 12,13 This API acts as an antibiotic, being widely used in the treatment of tuberculosis and leprosy, two diseases with high incidence in developing countries.…”