Laboratorios Liconsa SA

Nausea and vomiting of pregnancy is a common disease that affects many women suffering from mild to severe symptoms. Amongst the different treatments, a fixed dose combination of doxylamine and pyridoxine has been proven safe and effective although the mechanism of action is not well established. There are different pharmaceutical dosage forms in the European market. The objective of this study was to compare the characteristics of a capsule formulation, Cariban® and a tablet formulation, Xonvea® to evaluate the potential impact of their release profiles on their onset of action.

10 mg/10 mg of doxylamine succinate/pyridoxine hydrochloride capsules (Cariban®) and tablets (Xonvea®) were used as reference materials. Appearance, mass, composition, and in vitro dissolution profiles were compared. Bibliographic data from 4 pharmacokinetic studies of Xonvea® and 1 pharmacokinetic study of Cariban® was reviewed.

In vitro dissolution studies showed significant differences in dissolution profiles of tablets and capsules. The later exhibiting some release of both drug substances in acid conditions followed by a non-complete release after a total of 3 hours while the tablets demonstrated gastro-resistant properties and rapid API release in about 20-30 minutes after the acid stage. Comparison of PK data showed greater Cmax for pyridoxine.

At pH 6.8, complete and faster release of the fixed dose combination for Xonvea® gastro-resistant tablets compared to Cariban® capsules could possibly explain the greater Cmax observed in vivo for the tablet's formulation. This could translate into faster onset of action and relief of nausea for pregnant women taking the tablets vs. the capsules.

Capsule-based dry powder inhaler (DPI) products can be influenced by a multitude of interacting factors, including electrostatic charging. Tribo-charging is a process of charge transfer impacted by various factors, i.e., material surface characteristics, mechanical properties, processing parameters and environmental conditions. Consequently, this work aimed to assess how the charging behavior of capsules intended for inhalation might be influenced by environmental conditions. Capsules having different chemical compositions (gelatin and hydroxypropyl methylcellulose (HPMC)) and distinct inherent characteristics from manufacturing (thermally and cold-gelled) were exposed to various environmental conditions (11%, 22% and 51% RH). Their resulting properties were characterized and tribo-charging behavior was measured against stainless steel and PVC. It was observed that all capsule materials tended to charge to a higher extent when in contact with PVC. The tribo-charging of the thermally gelled HPMC capsules (Vcaps® Plus) was more similar to the gelatin capsules (Quali-G™-I) than to their HPMC cold-gelled counterparts (Quali-V®-I). The sorption of water by the capsules at different relative humidities notably impacted their properties and tribo-charging behavior. Different interactions between the tested materials and water molecules were identified and are proposed to be the driver of distinct charging behaviors. Finally, we showed that depending on the capsule types, distinct environmental conditions are necessary to mitigate charging and assure optimal behavior of the capsules.