Formulation and characterization of piroxicam/cyclodextrin taste masked oral lyophilisates

Abstract

Oral lyophilisates are one of the orodispersible tablets produced by lyophilization technique. Due to their porous structure, they instantly disintegrate when contacting saliva. Generally, they are suitable for drugs with a short onset of action, such as nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, formulations of piroxicam lyophilisates and their properties were investigated. Because piroxicam is classified as a low solubility but high permeability drug, a solubility enhancing agent should be included in the formulation. The influence of β-cyclodextrin (βCD) and hydroxypropyl-β-cyclodextrin (HPβCD) on disintegration time and morphology of piroxicam lyophilisates was studied. Furthermore, the satisfactory taste-masking efficiency of HPβCD in piroxicam lyophilisates was studied by sensory test. The effect of matrix polymer mixtures on disintegration time was previously evaluated. The appropriate ratio of polymer mixture, i.e., gelatin and hydroxypropyl methylcellulose (HPMC), provided lyophilisates with the fastest disintegration time (<30 s) was designated for further studies. The presence of both CDs decreased disintegration time and modified the surface and matrix of lyophilisates. With the theoretical study based on molecular mechanics methods and the investigation through the chemical shift of protons using nuclear magnetic resonance (NMR), piroxicam formed inclusion complexes with both βCD and HPβCD. Dissolution profiles of piroxicam/HPβCD lyophilisates revealed improved piroxicam solubility by inclusion complex formation. Finally, the piroxicam/HPβCD lyophilisates demonstrate the bitterness suppression in healthy volunteers.