DESIGN AND IN VITRO EVALUATION OF MULTIPARTICULATE SYSTEM FOR THE CHRONOMODULATED DELIVERY OF LORNOXICAM

Abstract

In view of chronobiological considerations of rheumatoid arthritis, the present study deals with the design and evaluation of multiparticulate system for the chronomodulated delivery of lornoxicam.  The basic design is based on the Pulsincap technology and consisted of formaldehyde treated insoluble hard gelatin capsule body filled with tripolyphosphate cross-linked chitosan microspheres of lornoxicam and sealed with a hydrogel tablet plug. The entire device was enteric coated, so as to prevent the variable gastric emptying time. The microspheres were found to be discrete, nearly spherical with rough surface characteristics.  Particle size, encapsulation efficiency and release rate of lornoxicam from the microspheres are dependent on the fabrication conditions of the microencapsulation. FT-IR, DSC and XRD studies revealed the compatibility of the drug with the excipients used.  The exposure of hard gelatine capsule bodies with formaldehyde for a period of 12 hrs was found to be optimum in maintaining the intactness of the capsule bodies in the simulated GI fluids. The lag time of the designed delivery system varied from 4-8 hrs and depended on the nature and concentration of the plugging material. The ejection of the plug was delayed with increase in the polymer concentration. Among the two polymers studied as plugging materials, guar gum exhibited better control in maintaining the lag time compared to xanthan gum. From the study it can be concluded that, the lag time be efficiently tailored by varying the concentrations of the polymers in the hydrogel plug for the chronomodulated delivery of lornoxicam.

Key Words: Rheumatoid arthritis; Lornoxicam; Microspheres; Chronomodulated delivery systems; Hydrogel plug; Lag time;