The influence of co-formers on the dissolution rates of co-amorphous sulfamerazine/excipient systems

Abstract

A comprehensive study on the dissolution properties of three co-amorphous sulfamerazine/excipient systems, namely sulfamerazine/deoxycholic acid, sulfamerazine/citric acid and sulfamerazine/sodium taurocholate (SMZ/DA, SMZ/CA and SMZ/NaTC; 1:1 molar ratio), is reported. While all three co-formers stabilize the amorphous state during storage, only coamorphization with NaTC provides a dissolution advantage over crystalline SMZ and the reasons for this were analyzed. In the case of SMZ/DA extensive gelation of DA protects the amorphous phase from crystallization upon contact with buffer, but at the same time prevents the release of SMZ into solution. Disk dissolution studies showed an improved dissolution behavior of SMZ/CA compared to crystalline SMZ. However, enhanced dissolution properties were not seen in powder dissolution testing due to poor dispersibility. Co-amorphization of SMZ and NaTC resulted in a significant increase in dissolution rate, both in powder and disk dissolution studies.

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

“…In other words, it is unclear if the behavior of those five drugs in CAMS with respect to co-formability, physical stability, and dissolution behavior can be directly translated to other drugs. ents to form strong molecular interactions with basic drugs (for example in [25,[31][32][33][34][35][36][37][38][39][40][41][42][43]). The organic acids used as co-formers differ in their number of carboxylic acid groups, which was hypothesized to lead to salt formation with a basic drug at different molar ratios.…”

The natural bile acid surfactant sodium taurocholate (NaTC) as a coformer in coamorphous systems: Enhanced physical stability and dissolution behavior of coamorphous drug-NaTc systems

“…It has been shown that the dissolution profile and bioavailability of ASDs can be significantly improved by using polymers with surface activity or mixtures of a polymer and a surfactant (Chauhan et al, 2005;Won et al, 2005). We have recently applied the natural bile acid surfactant sodium taurocholate (NaTC, Scheme 1) as a small-molecule coformer for a sulfa drug coamorphous system and demonstrated that coamorphous sulfamerazine-NaTC displays a significantly enhanced dissolution rate along with a high stability towards recrystallization (Gniado et al, 2016). We have now extended our coamorphization studies with NaTC to a wide range of active pharmaceutical ingredients (APIs).…”

Cocrystal Forms of the BCS Class IV Drug Sulfamethoxazole

“…Two of the co-amorphous systems, smz.hma and smz.cbz, recrystallized to starting material in the buffer and smz.da formed a gel on contact with the buffer. 6 Solubility measurements showed that the co-crystals had solubilities that were close to that of smz form I, Table S4. The solubility of smz form II was twice as high as that of smz FI.…”