Bulk, surface properties and water uptake mechanisms of salt/acid amorphous composite systems

Abstract

Developing amorphous pharmaceuticals can be desirable due to advantageous biopharmaceutical properties. Low glass transition temperature (Tg) amorphous drugs can be protected from crystallisation by mixing with high Tg excipients, such as polymers, or with salt forms. However, both polymers and salts can enhance the water uptake. The aim of this study was to formulate physico-chemically stable amorphous materials, by co-processing different proportions of sulfathiazole and its sodium salt to produce an optimum ratio, characterised by the best physical stability and lowest hygroscopicity. Both sulfathiazole and salt amorphised upon spray drying. At room temperature, sulfathiazole crystallised within 1h at <5% relative humidity while the salt deliquesced when exposed to ambient humidity conditions. In the case of composite systems, FTIR spectroscopy, thermal and surface analysis suggested interactions with an acid:salt stoichiometry of 1:2. Increasing proportions of salt raised the Tg, enhancing the storage stability, however this was opposed by an enhanced hygroscopicity. The water uptake mechanism within the different amorphous systems, analysed by fitting the water sorption isotherms with the Young and Nelson equation, was dependent on the ratio employed, with the salt and the acid facilitating absorption and adsorption, respectively. Tuning the properties of amorphous salt/acid composites by optimising the ratio appears potentially promising to improve the physical stability of amorphous formulations.

A novel hot-melt extrusion formulation of albendazole for increasing dissolution properties

“…All the raw materials and extruded samples were analysed by Karl-Fischer titration to determine the water content, since the well-known hygroscopicity of some pharmaceutical grade polymers such as polyvinylpyrrolidone (PVP) can be a limitation due to its influence on the stability of amorphous solid dispersions (Bianco et al, 2013). Low water content values of dosage forms containing hygroscopic polymeric materials such as PVP constitute a crucial parameter to be evaluated as there is evidence indicating that intramolecular bonds of polymeric materials and therefore the polymer free volume and other properties like plasticity or elasticity can be affected by increases in water content (Szakonyi and Zelko, 2012).…”

Evaluation of the recrystallization kinetics of hot-melt extruded polymeric solid dispersions using an improved Avrami equation

“…surface free energy, surface area, etc. ), water uptake ability and mechanisms of the polymer carrier 44 , might be the causes of different recrystallization inhibition abilities for the amorphous solid dispersion system under the same RH conditions, which will be the focus of our future studies.…”

Optimising the in vitro and in vivo performance of oral cocrystal formulations via spray coating

“…The optimised SDM:4ASA cocrystal-coated beads (25 mg) were placed in uncapped HPLC vials and introduced into test chambers exposed to different conditions of temperature and humidity: 50/50, 60/30, 70/11, 70/75, 80/30, 80/50 (°C/ % RH). The desired humidity was achieved by using Amebis humidity capsules (Amebis Ltd., Ireland) which were placed into Amebis sample holders, which in turn were put inside ovens at the selected temperature in order to ensure that the RH equilibrium was reached prior to the aging of the formulations [23].…”