Cross-linked Alginate Beads of Montelukast Sodium Coated with Eudragit for Chronotherapy: Statistical Optimization, and Evaluation.

INTRODUCTION

Chronotherapy is the administration of medication according to the biological rhythm to maximize pharmacological effects and minimize side effects. The objective of the current investigation is to prepare delayed-release beads (DRBs) containing montelukast sodium (MKS) for chronotherapy of asthma.

METHODS

Delayed-release beads of alginate were prepared using a simple method, i.e., ionotropic gelation. The effect of cross-linking agents (zinc or calcium ions) and the concentration of chitosan on the properties of the beads were investigated. The prepared beads were coated by a polymer having pHindependent solubility, i.e., Eudragit RSPO and Eudragit RLPO in different ratios to achieve the desired lag time of 4-5 h. Beads were evaluated for surface morphology, practical yield, encapsulation efficiency, XRD, and in vitro release study. The pharmacokinetic study was carried out on New Zealand white male rabbits.

RESULTS

No major differences in the drug release profile were observed between Ca++ and Zn++ crosslinked beads. However, a slight slow release was seen in the case of chitosan-reinforced beads. MKS released from cross-linked alginate beads was slightly altered with sodium alginate concentration, crosslinking time, and talc. At a higher alginate concentration, slow drug release was observed, whereas the addition of talc to alginate increased the release rate. The in vitro release study showed that the optimal formulation of DRBs has a lag time of 4.5 h, and the release at 6 h was found to be 74.9%. In vivo pharmacokinetic study of the beads showed T at 7 h with an initial lag time of 4 h.

CONCLUSION

When dosed at sleep time, the prepared cross-linked beads may deliver montelukast sodium required to relieve early morning symptoms in asthmatic patients.