Drug loading mechanism of hollow hydroxyapatite microcapsules

Inorganic hydroxyapatite microcapsules are innovative drug delivery devices tailored for oral drug delivery. They were designed as novel excipients, the so-called template inverted particles (TIP), to assist in preparing the orally disintegrating tablets. This study characterized the drug loading capacity using 11 clinically relevant drugs covering all BCS classes, focusing on midazolam HCl, ivermectin, ibuprofen, and metronidazole benzoate. An exceptionally high drug loading capacity of 45 % (v/v) was observed for all studied drugs. Compaction of loaded TIP resulted in mechanically stable tablets with tensile strengths of up to 6 MPa and disintegrating in a few seconds upon contact with water. Accelerated dissolution of encapsulated drugs is explained by the microcapsules’ high specific surface area and the inhibited crystallization due to spacial constraints for some tested drugs. Efficient drug loading into TIP’s internal hollow cavity structure is facilitated by a self-loading mechanism, eliminating the need for complex, drug-specific loading strategies. A mathematical model is presented to describe the self-loading mechanism of TIP, which is responsible for exclusive drug deposition within the cavity of the particles. We demonstrate that TIP, being a versatile and cost-effective platform technology, has the potential to facilitate the formulation development process of patient-friendly medicines.