Preparation and Characterization of Eudragit L100/S100 Coated Zafirlukast Pellets for Chronotherapy

Background:

The initial goal of the current research investigation was to design, develop oral formulation of Pulsatile Drug Delivery Systems (PDDS) for Zafirlukast with aim of treatment for asthma. Delivery system was designed as Pellets type of system with Immediate and extended release of drug occurs at after the lag time period. In chronic asthma condition patients suffered during the early morning hours (04.00 AM to 06.00 AM) so immediate release dosage forms are not suitable but the modified release formulation that is given at bed time and releases the drug as pulsed manner despite to wake up the patient.

Materials and Methods:

In this present investigation, Zafirlukast pellets were prepared using Extrusion-Spheronization method, seal coating with HPMC E5 and enteric coating with Eudragit L100 and Eudragit S100 polymers by Fluid Bed Processor (FBP) for extending lag period prior the drug release. The formulations were designed as pellets of Immediate (IR) and Extended (ER) release of drug following lag time. IR pellets were designed as drug release immediate after the lag time and ER tablets designed as extend the release of drug from the pellets after the lag time.

Results:

The optimised formulations of FZ9 showed release of drug 99% at 6 hr with 04 hr lag time and FZX12 showed 99% of drug release at 11.5 hr with 4.5 hr lag time. The drug-excipient compatibility for the formulation was assessed using FTIR and DSC; the results obtained shown that no chemical interactions among the drug and incorporated excipients. SEM Studies showed porous nature of extrudes and covered with coatings of seal, enteric polymers. As per ICH standards for optimized formulations, stability experiments were also conducted for 6 months at 40ºC at 75% RH and it was concluded to be stable.

Conclusion:

The designed pellets of both IR and ER release with enteric coating beneficial to patients with night time dosing that can prevent the asthma episodes at early morning and development of exacerbations.