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.