Effect of glucosamine HCl on dissolution and solid state behaviours of piroxicam upon milling

Piroxicam is a non-steroidal anti-inflammatory drug that is characterised by low solubility and high permeability. In order to improve the drug dissolution rate, the co-grinding method was used as an approach to prepare piroxicam co-ground in the carriers such as glucosamine hydrochloride. As, this amino sugar (glucosamine HCl) has been shown to decrease pain and improve mobility in osteoarthritis in joints, therefore, the incorporation of glucosamine in piroxicam formulations would be expected to offer additional benefits to patients. The effect of the order of grinding on the dissolution of piroxicam was also investigated. Co-ground drug and glucosamine were prepared in different ratios using a ball mill. The samples were then subjected to different grinding times. In order to investigate the effect of the grinding process on the dissolution behaviour of piroxicam, the drug was ground separately in the absence of glucosamine. Mixtures of ground piroxicam and unground d-glucosamine HCl were prepared. Physical mixtures of piroxicam and glucosamine were also prepared for comparison. The properties of prepared co-ground systems and physical mixtures were studied using a dissolution tester, FTIR, SEM, XRPD and DSC. These results showed that the presence of glucosamine HCl can increase dissolution rate of piroxicam compared to pure piroxicam. Generally, all dissolution profiles showed the fastest dissolution rate when ground piroxicam was mixed with unground glucosamine. This was closely followed by the co-grinding of piroxicam with glucosamine where lower grinding times showed the fastest dissolution. The solid state studies showed that the grinding of piroxicam for longer times had no effect on polymorphic form of piroxicam, whereas mixtures of piroxicam-glucosamine ground for longer times (60. min) converted piroxicam polymorph II to polymorph I.