Development of a Palatable, Bioequivalent Montelukast 5mg Zydis® Dosage Form

Purpose

Montelukast is indicated for the treatment of asthma and allergic rhinitis. It is available as a 4mg dose of granules for patients aged 6 to 23 months, 4mg chewable tablets for 2 to 5 year olds and 5mg chewable tablets for 6 to 14 year olds. Orally disintegrating tablets (ODTs) are frequently preferred due to ease of swallowing. In order for the drug to be delivered using an ODT such as Zydis®, a palatable product is required to facilitate patient compliance. The aim of this study was to investigate if a palatable Zydis® montelukast ODT could be developed. A chemically stable product with bioequivalence to the reference product was a prerequisite for success.

METHODOLOGY

Prototype freeze dried formulations containing montelukast (sodium salt) were manufactured using the Zydis® formulation and process1. Dissolution testing was performed on the prototype formulations using USP apparatus II (paddles) at 50rpm with 900ml 0.5%w/v sodium dodecyl sulphate. Assay and stability testing were performed by HPLC. A taste trial was conducted by a panel of 30 volunteers assessing the acceptability of a Zydis® ODT formulation and comparing with a montelukast 5mg chewable tablet (Singulair®) . The probe bioequivalence study was a single dose, open label, randomized, two period, two treatment crossover study in which 12 healthy adult subjects received two separate single dose administrations of montelukast sodium, following an overnight fast of at least 10 hours. Subjects received montelukast 5mg (sodium salt) Zydis® ODT and Singulair® 5mg reference product in a randomized fashion.

RESULTS AND DISCUSSION

Montelukast sodium was successfully incorporated into the Zydis® dosage form resulting in elegant ODTs with rapid disintegration properties (Figure 1). Stability and dissolution testing results were comparable or favorable to the Singulair® control (Table 1 and Figure 2). The results of the 30 subject taste panel were positive, demonstrating Taste Trial – Zydis® Montelukast 5mg vs Singulair® 5mg a highly palatable formulation (Figure 3 and Table 2). The probe bioequivalence study in 12 healthy subjects showed that the Zydis® product was bioequivalent to the Singulair® comparator (Figure 4).

CONCLUSIONS

This study confirmed that montelukast (sodium salt) can be successfully incorporated into the Zydis® ODT. The formulation was chemically stable, had a good taste profile and was bioequivalent to the Singulair® reference product. The work demonstrated the feasibility of developing a commercially viable ODT formulation of montelukast 5mg. It is expected that a Zydis® ODT montelukast 4mg and 10mg formulation would be equally as successful.

REFERENCES

1. H.Seager, Drug-delivery Products and the Zydis® Fast-dissolving Dosage Form, J.Pharm.Pharmacol., 50 (1998) 375-382.

 

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Related Topics and Keywords

Bioequivalent Montelukast, Catalent, Catalent Pharma Solutions, ODT, ODTs, oral disintegrating tablet, oral disintegrating tablets, orally disintegrating tablets, Palatable, taste masking, Zydis