Abstract
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° 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 ≥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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
A PATH/WHO report on Intradermal Delivery of Vaccines: A Review of the Literature and the Potential for Development for Use in Low- and Middle-Income Countries. http://www.path.org/files/TS_opt_idd_review.pdf (accessed 11/16/2009).
Andrianov AK, DeCollibus DP, Gillis HA, Kha HH, Marin A, Prausnitz MR, et al. Poly[di(carboxylatophenoxy)phosphazene] is a potent adjuvant for intradermal immunization. Proc Natl Acad Sci. 2009;106:18936–41.
Kim YC, Quan FS, Compans RW, Kang SM, Prausnitz MR. Formulation and coating of microneedles with inactivated influenza virus to improve vaccine stability and immunogenicity. J Control Release. Epub ahead of print. 2009.
Quan FS, Kim KC, Yoo DG, Compans RW, Prausnitz MR, Kang SM. Stabilization of influenza vaccine enhances protection by microneedle delivery in the mouse model. PLos One. 2009;25:e7152.
Gill HS, Prausnitz MR. Coating formulations for microneedles. Pharm Res. 2007;24:1369–80.
Gill HS, Prausnitz MR. Coated microneedles for transdermal delivery. J Control Release. 2007;117:227–37.
Cosman F, Lane NE, Bolognese M, Zanchetta J, Garcia-Hernandez PA, Sees K, et al. Effect of transdermal teriparatide administration on bone mineral density in postmenopausal women. J Clin Endocrinol Metab. In press.
Trautman JC, Wright CT, Cormier M. Method and apparatus for coating skin piercing microneedles. US Patent 6,855,372. 2002.
Trautman JC, Wright CT, Cormier M. Method and apparatus for coating skin piercing microneedles. US Patent 7,435,299. 2002.
Ameri M, Daddona PE, Maa Y-F. Demonstrated solid-state stability of parathyroid hormone PTH(1-34) coated on a novel transdermal microprojection delivery system. Pharm Res. 2009;26:2454–63.
Ameri M, Wang X, Maa Y-F. Effect of irradiation on parathyroid hormone PTH(1-34) coated on a novel transdermal microprojection delivery system to produce a sterile product—adhesive compatibility. J Pharm Sci. In print. 2009.
Cormier M, Neukermans AP, Block B, Theeuwes FT, Amkraut A. A device for enhancing transdermal agent delivery or sampling. EP0914178B1. 2003.
Nabuchi Y, Fujiwara E, Kuboniwa H, Asoh Y, Ushio H. The stability and degradation pathway of recombinant human parathyroid hormone: deamidation of asparaginyl residue and peptide bond cleavage at aspartyl and asparaginyl residues. Pharm Res. 1997;14:1685–90.
Cai K, Muller M, Bossert J, Rechtenbach A, Jandt KD. Surface structure and composition of flat titanium thin films as a function of film thickness and evaporation rate. Appl Surf Sci. 2005;250:252–67.
Textor M, Sitting C, Frauchiger V, Tosatti S, Brunette DM. Properties and biological significance of natural oxide films on titanium and its alloys. In: Brunette DM, editor. Titanium in medicine. New York: Springer; 2001. p. 171–265.
Ameri M, Lin W, Cormier MJN, Maa Y-F. Formulations for coated microprojections containing non-volatile counterions. US Patent 7,579,013. 2009.
Chaplin M. Acids, bases and the Henderson–Hasselbalch Equation. http://www.lsbu.ac.uk/biology/biolchem/acids.html (accessed 07/10/09), part of the online program by the London South Bank University, UK (accessed 07/10/09).
Tan MM, Corley CA, Stevenson CL. Effect of gelation on the chemical stability and conformation of leuprolide. Pharm Res. 1998;15:1442–548.
Barnes HA, Hutton JF, Walters K. An introduction to rheology. New York: Elsevier; 1989.
Reiger F. Determination of rheological parameters from measurements on a viscometer with coaxial cylinders—choice of the reference radius. Acta Polytech. 2006;46:22–4.
ACKNOWLEDGMENTS
The authors are indebted to Dr. WeiQi Lin for her assistance in HPG PK study, Dr. Michel Cormier for his contributions to the acetate depletion theory and PTH(1-34) charge profile calculation, and Mr. Perry Weissburg for acetate content analysis.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ameri, M., Fan, S.C. & Maa, YF. Parathyroid Hormone PTH(1-34) Formulation that Enables Uniform Coating on a Novel Transdermal Microprojection Delivery System. Pharm Res 27, 303–313 (2010). https://doi.org/10.1007/s11095-009-0019-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11095-009-0019-8