Title:Cross-linked Alginate Beads of Montelukast Sodium Coated with Eudragit
for Chronotherapy: Statistical Optimization, In vitro and In vivo Evaluation
Volume: 19
Issue: 10
Author(s): Om Prakash Ranjan*, Nitesh Kumar and Vivek Dave
Affiliation:
- Department of Pharmaceutics, Manipal College of Pharmaceutical Science, MAHE, Manipal - 576104, Karnataka,
India
- Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and
Research (NIPER), Guwahati - 781101, Assam, India
Keywords:
Montelukast sodium, cross-linked, sodium alginate, beads, chronotherapy, asthma.
Abstract:
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 Tmax 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.
