Development of a Zydis® Tadalafil Freeze Dried Orally Disintegrating Tablet

Purpose

Tadalafil is a phosphodiesterase type 5 (PDE5) enzyme inhibitor indicated for the treatment of erectile dysfunction and benign prostatic hyperplasia (BHP). It is currently marketed by Eli Lilly as Cialis® and is available in dose strengths of 2.5mg, 5mg, 10mg and 20mg as film coated tablets. Orally Disintegrating Tablets (ODTs) are frequently preferred due to their ease of swallowing, convenience and discretion associated with administering the tablets in the absence of water. The aim of this study was to investigate if a chemically stable Zydis® tadalafil 20mg ODT could be developed which has similar dissolution properties to Cialis®.

METHODOLOGY

Prototype freeze dried formulations containing 20mg tadalafil were manufactured using the Zydis® formulation and process1. Dissolution testing was performed on the Zydis® prototype formulation and Cialis® 20mg using USP apparatus II (paddles) at 50rpm with 1000ml 0.5% w/v sodium dodecyl sulphate. Assay and stability testing was conducted on both the Zydis® prototype and the Cialis® reference product by HPLC. Disintegration testing was performed on the Zydis® freeze dried prototypes using the USP test. Dispersion testing was performed on the Zydis® freeze dried prototype by adding the tablets to a beaker of purified water at both 20°C and 37°C (± 0.5°C) and recording the time for the unit to become fully wetted.

Results and Discussion

Tadalafil was successfully incorporated into the Zydis® dosage form, resulting in ODTs with rapid dispersion and disintegration times (Figure 1, Table 1). The tablets had an elegant appearance, leaving no residue behind when removed from the blister pocket (Figure 2). Stability and dissolution testing results were equivalent to the Cialis® 20mg control (Table 2 and Figure 3).

Conclusions

This study confirmed that tadalafil 20mg can be successfully incorporated into the Zydis® ODT. The formulation was chemically stable and had a dissolution profile equivalent to the Cialis® reference product. The work demonstrated the feasibility of developing a commercially viable ODT formulation of tadalafil 20mg. Based on the positive results of the tadalafil 20mg, it is anticipated that the 2.5mg, 5mg and 10mg dose strengths would also be 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

benign prostatic hyperplasia, BHP, Cialis®, Eli Lilly, enzyme inhibitor, erectile dysfunction, ODTs, orally disintegrating tablet, PDE5, phosphodiesterase type 5, Tadalafil Freeze Dried, Zydis