An assessment of triboelectrification effects on co-ground solid dispersions of carbamazepine

• The cogrinding process produced polymorphic transformations in CBZ.
• GLU exhibited lower charge densities as compared to CBZ.
• Net charge density decreases with increasing CBZ content up to 30% above which net charge density increases.
• Technique could be used to determine appropriate formulations that improve handling.

One of strategies adopted to improve the dissolution rates of poorly soluble drugs is by co-grinding the drug with a hydrophilic carrier. However, the introduction of mechanical forces during the grinding process can lead to changes in the physicochemical characteristics as well as an increase in the surface free energy of the ground particles, which causes an alteration in the electrostatic properties of these particles. The solid state characteristics of glucosamine hydrochloride (GLU) and carbamazepine (CBZ) and their co-ground mixtures were studied using DSC, XRPD and SEM. These revealed that polymorphic transformations occurred due to the grinding process. The influence of grinding time on the triboelectrification properties of the formulations was also studied. Both pure CBZ and GLU powders were predominantly electro-positively charged and their charging properties increased with increasing grinding time. CBZ:GLU physical mixtures exhibited complicated bipolar charging behaviour, however, when subjected to grinding, these mixtures demonstrated mainly electronegative charge properties. The influence of both grinding time and CBZ content within CBZ:GLU mixtures was examined. The value of net-electronegative-charge density of CBZ:GLU mixtures was shown to increase with grinding time and/or when increasing the percentage proportion of CBZ up to 30% w:w. This study helps to provide information about the handling of these formulations and gives a formulator tools to ascertain appropriate ratios for handling and possible simultaneous dissolution improvements.

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