Abstract
Objective: In view of chronobiological considerations of nocturnal asthma, the present study deals with the development and evaluation of multiparticulate system for the chronomodulated delivery of terbutaline sulphate.
Methodology: The basic design is based on the Pulsincap technology and consisted of formaldehyde treated insoluble hard gelatin capsule body filled with glutaraldehyde cross-linked carboxymethyl chitosan microspheres of terbutaline sulphate and sealed with a hydrogel tablet plug. The entire device was enteric coated, so as to prevent the variable gastric emptying time.
Results: The glutaraldehyde cross-linked carboxymethyl chitosan microspheres appeared to be roughly spherical with the size range of 4.63±0.48 to 11.75±0.92µm. The prepared microspheres possessed good yield and high encapsulation efficiency. Particle size, encapsulation efficiency and release rate are dependent on the fabrication conditions of the microspheres. FT-IR and XRD studies revealed the compatibility of the drug both in the physical mixture and the formulation form. Drug release from the microspheres depended on the core: coat ratio, reaction time and the rotational speed used in the preparation of microspheres. Formaldehyde treatment efficiently rendered the hard gelatine capsule bodies water insoluble. The ejection of the plug from the chrnomodulated delivery system depended on the nature and concentration of polymer used in the preparation of table plug. A lag time of 3-8hrs was observed for the chronomodulated delivery systems prepared with different hydrogel plugging materials. Among the different polymers studied, HPC showed highest lag time compared to HPMC K4 M and sodium alginate.
Conclusion: The results of the study conclusively proved the suitability of carboxymethyl chitosan microspheres and the adopted Pulsincap technology in the development of chronomodulated delivery systems for terbutaline sulphate in the treatment of nocturnal asthma.
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