Abstract

FORMULATION, OPTIMIZATION OF MONTELUKAST LOADED MICROSPHERES USING BOX–BEHNKEN DESIGN: IN VITRO STUDY FOR TREATMENT OF NOCTURNAL ASTHMA

Kinjal Gandhi* and Dr. P. Ajith Kumar

ABSTRACT

Background: In nocturnal asthma, a condition prevalent in two-thirds of the asthmatics, a drug delivery system that can release the drug at a predetermined time to guarantee therapeutic efficacy is a prerequisite. This can be achieved by developing a pulsed release system capable of delivering the drug at the required time after a well-defined lag time. The main objective of the present investigation was to create Montelukast-loaded microspheres with the smallest particle size, highest drug entrapment efficiency, and highest percent drug release after 6 hours. Methods: The microsphere was manufactured using the solvent evaporation process. For optimization, the "Box–design" Behnken (3 factors, 3 levels) was used. The drug: polymer ratio (X1), surfactant concentration (X2), and stirring speed (X3) were considered independent factors, while entrapment efficiency (Y1), percent drug release after 6 hours (Y2), and particle size (Y3) were considered dependent variables. Microspheres with MKS were created and optimised. Compatibility tests, morphological, micrometric, and characterisation tests, as well as in vitro release tests, were undertaken on the optimised microspheres. Results: For the optimised batch, the entrapment efficiency, percent drug release after 6 hours, and particle size were 84.63%, 62.32 %, and 100.44µm, respectively. There was no interaction between the medication and the polymer, according to the FTIR and DSC studies. For the optimised formulation, the cumulative drug releases were found to be 93.13±0.86%. Chronomodulated pulsatile capsule was filled with MKS microspheres (optimised formulation) corresponding to 10 mg, followed by Abelmoschus Esculentus plug, and finally closing the mouth with a soluble cap produced a chronomodulated pulsatile capsule. Drugs from CMPs were released at rates of 88.47, 95.02, and 95.82 % in vitro. Conclusion: The results demonstrate that the device is effective of delaying drug release for a configurable amount of time, averting a rapid rise in the prevalence of asthmatic attacks during the early hours of the morning, when the probability of asthmatic attacks is maximum.

Keywords: Montelukast sodium, Microspheres, Box Behnken Design, Solvent.