Asthma

1. Asthma • Most common chronic illness of childhood, affecting approximately 10% children. • Available preventive therapies for persistent asthma include inhaled delivery system containing corticosteroids and long acting beta agonists. • Adherence with inhaled therapies is poor in pediatrics. • Orally active leukotriene receptor antagonists are shown to be effective in pediatric patients.

2. Montelukast sodium • Indications: Prophylaxis and treatment of asthma, exercise induced asthma, in Aspirin sensitive asthamatics. • Potent, selective and orally acting leukotriene receptor antagonist. • Acts by inhibiting physiological actions of LTC4, LTD4 and LTE4 at the Cystiene Leukotriene levels (Cys LT1 receptor). • Dose: Adults :- 10 mg OD Child 6-14 yrs:- 5 mg OD 2-5 yrs :- 4 mg OD • Rapid oral absorption with mean oral bioavailability of 64 %.

3. Objective of incevtigation • Formulation palatable mouth dissolve tablets of Montelukast Sodium. • Evaluate the efficacy of Ion exchange resin (Indion 414) as superdisintegrant over the extsting ones in mouth dissolve tablets.

4. Melt in Mouth Tablets These are solid dosage forms that dissolve or disintegrate within a Minute in the oral cavity without the need of water or chewing and have a pleasant taste. Advantages offered • Ease of swallowing • Ease of handling • Improved patient compliance • Line extension and lifecycle management.

5. Ion Exchange Resins • Safe for oral consumption. • Indion 414 is a water insoluble, chemically crosslinked acrylic copolymer matrix with carboxylic acid as functional group (Potassium form). • Swelling property of ion exchange resins makes them ideal candidate as superdisintegrants.

6. Analytical Method Development UV Spectrophotometric method for analysis of Montelukast Sodium Detection lmax 342 nm Linearity range 10-50 mg/ml Slope ± SD 0.0194 ± 0.0014 Regression coefficient 0.999

7. Formulation Development • Montelukast Sodium was mixed in geometric proportions with superdisintegrants, sweetners, diluent, flavors and lubricants. Various concentrations of superdisintegrants were employed to arrive at an optimum disintegration time. • Blend was screened through 40 #. • Compressed on Cadmach single station tablet press machine equipped with 9 mm flat beveled punches.

8. Formulation details of melt in mouth tablets of Montelukast Sodium The tablet weight was fixed to 150 mg. Montelukast Sodium Active Aspartame Sweetner Avicel PH102 Diluent Indion 414 Superdisintegrant Menthol Coolant Instacoat Strawberry flavor Flavor Supplied by Ideal Cures Pvt Ltd. Talc Lubricant Magnesium stearate Anti adherent Aerosil Glidant

9. Comparison of Indion 414 with existing superdisintegrants

10. Evaluation of the Optimized Formulation Parameter Observation Appearance Flat beveled tablets off white in color Texture Smooth Taste Palatable Dimensions 9 mm in diameter Weight variation (mg) ± SD 150 ± 2.87 Hardness (kg/cm2) 3-4 In-vitro disintegration time (sec) 20 Drug content (%) 101.2% ± 1.34 Drug release (%) Apparatus – USP Type II Medium – 500 ml Water 95% rpm – 100, Time – 30 min

11. Conclusion • Patient compliant and palatable melt in mouth tablets of Montelukast Sodium having optimum physicochemical properties were formulated. • Ion exchange resin (Indion 414) could be successfully used as superdisintegrant, thus making the formulation cost effective. • The tablets exhibited an in-vitro disintegration time of 20 seconds. • The technology can also be easily employed for large-scale manufacturing.

12. Acknowledgements The authors thank • Ideal Cures Pvt. Ltd. for providing financial assistance towards this presentation and also for gift samples of Instacoat flavors. • Cipla Ltd, Mumbai for gift sample of Montelukast Sodium. • Ion Exchange India Ltd for gift sample of Ion Exchange resin.