Use of cyclodextrin to achieve a taste masked, bioequivalent Cetirizine HCl 10mg Zydis® dosage form Catalent Pharma Solutions L.Grother, K.Hau, P.Axe, J.F.Baker

OBJECTIVES

Cetirizine HCl is a bitter drug indicated for the treatment of allergies. Due to the nature of allergic episodes, medication is often required at unpredictable times. Consequently dose forms such as orally disintegrating tablets (ODTs) are frequently preferred by patients due to the greatly enhanced convenience they provide. In order for the drug to be delivered using an ODT such as the Zydis® dosage form, effective taste masking is required. The aim of this study was to investigate if cyclodextrin could be used to taste mask cetirizine HCl 10mg when formulated in a freeze dried ODT (Zydis®). A chemically stable product with bioequivalence to the reference product was a prerequisite for success.

METHODOLOGY

Prototype freeze dried formulations containing cyclodextrin were manufactured using the Zydis® formulation and process1. Dissolution testing was performed on the prototype formulations using USP apparatus II (50rpm) with 900ml purified water.Assay and stability testing were performed by HPLC. A taste trial was conducted using 2 betacyclodextrin formulations (high and low flavour level) by a panel of 30 volunteers. The probe bioequivalence study was a single dose, open label, randomized, two period, two treatment crossover study in which 10 healthy adult subjects received two separate single dose administrations of cetirizine HCl 10mg, following an overnight fast of at least 10 hours. Subjects received Cetirizine HCl 10mg Zydis® ODT and Zirtek® 10mg reference product in a randomized fashion.

RESULTS AND DISCUSSION

The cetirizine and cyclodextrin were 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 Zirtek® control (Figure 2 and 3).

The results of the 30 subject taste panel were positive, demonstrating that taste masking had been achieved with the addition of cyclodextrin (Figure 4a and 4b).

The probe bioequivalence study in 10 healthy subjects showed that the Zydis® product was bioequivalent to the Zirtek® comparator (Figure 5).

 

Figure 1. Dispersion Test, <2 Seconds at 37°C

 

Figure 2. Stability Data of Cetirizine HCl Products Stored for 6 Months at 40°C /75%RH

 

Figure 2. Stability Data of Cetirizine HCl Products Stored for 6 Months at 40°C /75%RH

 

Figure 4a. Taste Trial Questionnaire – Data Plot

 

Figure 4b. Taste Trial Questionnaire – Data Table

 

Figure 5. Mean Plasma Concentrations – Fasted Bioequivalence Study

(Zydis® Tablet vs Zirtek® Tablet N=10)

 

CONCLUSIONS

This study confirmed that cyclodextrin can be successfully incorporated into the Zydis® ODT.

The formulation was chemically stable, taste masked and bioequivalent to the Zirtek® reference product. The work demonstrated the feasibility of developing a commercially viable ODT formulation of cetirizine HCl 10mg.

This study also confirmed that cyclodextrin can be used to as an additional taste masking strategy to allow the formulation of bitter APIs in the Zydis® dosage form.

 

REFERENCES

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

Zirtek is a registered trademark of UCB Pharma, S.A.

© 2013 Catalent Pharma Solutions. All rights reserved.

 

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Related Topics and Keywords

cetirizine, cyclodextrin, ODT, oral disintegrating tablet, Prototype freeze dried formulations, taste mask, taste masking, Zydis