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.

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 %.

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.

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.

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.

Analytical Method Development

UV Spectrophotometric method for analysis of Montelukast Sodium

Detection max 342 nm

Linearity range 10-50 g/ml

Slope ± SD 0.0194 ± 0.0014

Regression coefficient 0.999

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.

Formulation details of melt in mouth tablets of Montelukast Sodium

The tablet weight was fixed to 150 mg.

Montelukast Sodium ActiveAspartame SweetnerAvicel PH102 DiluentIndion 414 SuperdisintegrantMenthol CoolantInstacoat Strawberry flavor FlavorSupplied by Ideal Cures Pvt Ltd.Talc LubricantMagnesium stearate Anti adherentAerosil Glidant

Comparison of Indion 414 with existing superdisintegrants

SuperdisintegrantsAppearance of

tablet In-vitro disintegration

time (sec)

Indion 414 Smooth 20

Sodium Starch Glycolate Smooth 15

Croscarmellose sodium Smooth 15

Crospovidone Pitted 10

Evaluation of the Optimized Formulation

Parameter Observation

Appearance Flat beveled tablets off white in colorTexture SmoothTaste PalatableDimensions 9 mm in diameterWeight variation (mg) ± SD 150 ± 2.87Hardness (kg/cm2) 3-4In-vitro disintegration time (sec) 20Drug content (%) 101.2% ± 1.34Drug release (%)Apparatus – USP Type IIMedium – 500 ml Water 95%rpm – 100, Time – 30 min

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.

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.