Parathyroid hormone PTH(1-34) formulation that enables uniform coating on a novel transdermal microprojection delivery system.

PURPOSE

Assess formulation parameters to enable >24-h continuous accurate and uniform coating of PTH(1-34) on a novel transdermal microprojection array delivery system.

METHODS

Surface activity and rheology of the liquid formulation was determined by contact angle measurement and cone-plate viscometry. The formulation's delivery performance was assessed in vivo using the hairless guinea pig model. Peptide gelation was investigated by rheological and viscoelastic behavior changes.

RESULTS

Accurate and uniform coating was achieved by formulating the liquid formulation to a preferred contact angle range of 30-60 degrees with a surfactant and by establishing a Newtonian fluid (defined as a fluid maintaining a constant viscosity with shear rate and time) with a viscosity of > or =20 cps via adjusting the peptide concentration and using an appropriate acidic counterion. A non-volatile acidic counterion was found critical to compensate for the loss of the volatile acetate counterion to maintain the peptide formulation's solubility upon rehydration in the skin. Finally, the 15.5% w/w PTH(1-34) concentration was found to be the most physically stable formulation (delayed gelation) in the roll-coating reservoir. With a properly designed coating reservoir for shear force reduction, the liquid formulation could last for more than 24 h without gelation.

CONCLUSIONS

The study successfully offered scientific rationales for developing an optimal liquid formulation for a novel titanium microprojection array coating process. The resultant formulation has an enduring physical stability (>24 h) in the coating reservoir and maintained good in vivo dissolution performance.