Preparation of agglomerated crystals for improving flowability and compactibility of poorly flowable and compactible drugs and excipients

Abstract

Agglomerates of naproxen, carbamazepine and lactose were developed by two spherical crystallization techniques, i.e., a spherical agglomeration method for carbamazepine and an emulsion diffusion method for naproxen and lactose. Physical characteristics of the crystals were studied for the morphology of crystals using scanning electron microscope, for the identification of polymorphism by X-ray powder diffraction (XRPD) and for thermodynamic properties using differential scanning calorimetery (DSC). The results showed that the flow and packing properties of agglomerates, represented in terms of the angle of repose and changes in tapping density, were much improved by these techniques compared with those of conventional crystals. This may be due to the spherical shape of agglomerated particles, since the area of contact in the powder bed for spherical agglomerates was smaller than that for other crystal shapes. Under static compression the acceptable tablet with a sufficient strength was produced successfully without capping, although the capping occurred with the original unagglomerated crystals. The improved compactibility of agglomerates was attributed to their structural characteristics. Scanning electron microscope showed that the agglomerates were comprised of small crystals and this particular structure was responsible for large relative volumes change which occurred during the early stage of the compression process, as a consequence of fragmentation. XRPD and DSC results showed that during the agglomeration process, naproxen did not undergo any polymorphic changes. XRPD and DSC results for carbamazepine and lactose revealed that during the agglomeration process, carbamazepine Form III changed to Form I and some of α-lactose monohydrates were converted to anhydrous β-lactose.