Creating systemic oral transmucosal drug delivery strategies: Case study of APL-130277

Authors

  • Anthony Giovinazzo Cynapsus Therapeutics, Inc.
  • Nathan Bryson Cynapsus Therapeutics, Inc.
  • Timothy Tankosic Aqua Partners LLC

DOI:

https://doi.org/10.5912/jcb556

Keywords:

sublingual, oral transmucosal, drug delivery, apomorphine, Parkinson's

Abstract

This article addresses the strategic application of systemic oral transmucosal* (i.e., sublingual and buccal) drug delivery. Circumvention of first-pass hepatic metabolism in the gut, rapid onset of action, easy access via the oral cavity, easy administration for patients with dysphagia and a high level of patient acceptance are the principal advantages of the oral transmucosal route. Key clinical and commercial strategies driving the development of oral transmucosal formulations are addressed. A case study of Cynapsus Therapeutics' APL-130277, a sublingual apomorphine formulation in clinical development for Parkinson's disease exemplifies the scientific, clinical and commercial considerations for systemic oral transmucosal drug delivery.

*Note: In this article, oral transmucosal delivery refers to systemic drug delivery through the sublingual or buccal mucosa. Local delivery to the oral mucosa is not included.

References

Mathias, N.R. and Hussain, M.A. (2010) Non-invasive Systemic Drug Delivery: Developability Considerations for Alternate Routes of Administration. Journal of Pharmaceutical Sciences 99: 1–20.

Dodou, K. (2012) Research and developments in buccal and sublingual drug delivery systems. The Pharmaceutical Journal 288:446.

Zhang H., Zhang J. and Streisand, J.B. (2002) Oral mucosal drug delivery: Clinical pharmacokinetics and therapeutic applications. Clinical Pharmacokinetics 41: 661–680.

Narang, N. and Sharma, J. (2011) Sublingual mucosa as a route for systemic drug delivery. International Journal of Pharmacy and Pharmaceutical Sciences 3(Suppl 2): 18-22.

Patel, V.F., Liu, F. and Brown, M.B. (2011) Advances in oral transmucosal drug delivery. Journal of Controlled Release 153(2): 106-116.

Amir H. Shojaei et al (2001) Systemic Drug delivery via the buccal mucosal route. Pharmaceutical Technology June issue: 70-81. www.pharmaportal.com

Ilavarasan, P., Ezhumalai, K. and Rajalakshmi, A.N. (2011) Buccal patches as emerging trend. International Journal Of Pharmacy & Technology 3(2): 973-986.

Madhav, N.V. et al (2009) Orotransmucosal drug delivery systems: a review. Journal of Controlled Release 16;140(1): 2-11.

Pather S.I., Rathbone, M.J. and Senel, S. (2008) Current status and the future of buccal drug delivery systems. Expert Opinion on Drug Delivery 5:531–542.

Nicolazzo, J.A., Reed, B.L. and Finnin, B.C. (2005) Buccal penetration enhancers—How do they really work? Journal of Controlled Release 105:1–15.

Dali, M.M. et al (2006). A rabbit model for sublingual drug delivery: Comparison with human pharmacokinetic studies of propranolol, verapamil and captopril. Journal of Pharmaceutical Sciences 95:37-44.

Mizrahi, B. and Domb, A. J. (2008) Mucoadhesive polymers for delivery of drugs to the oral cavity. Recent patents on drug delivery & formulation 2(2): 108-19.

Holpuch, A.S. et al (2010) Nanoparticles for local drug delivery to the oral mucosa: proof of principle studies. Pharmaceutical Research 27: 1224–1236.

Moingeon, P. and Mascarell, L. (2012) Induction of tolerance via the sublingual route: mechanisms and applications (review article). Clinical and Developmental Immunology: 8 pp (Article ID 623474).

Thaxter, C. (July 25, 2011) Reckitt Benckiser Pharmaceuticals CEO presentation. http://www.rb.com/DocumentDownload.axd?documentresourceid=10470

Thomaselli, R. (Apr 9, 2012) Intermezzo rouses drug category with $100 million push. Advertising Age: http://adage.com/article/news/intermezzo-rouses-drug-category-100-million-push/234014/.

Drug information online. (2012) Drugs.com http://www.drugs.com/manufacturer/sepracor-inc-renamed-sunovion-pharmaceuticals-inc-163.html.

Stacy, M. and Silver, D. (2008) Apomorphine for the acute treatment of "off" episodes in Parkinson's disease. Parkinsonism & Related Disorders 14(2): 85-92.

Olanow, C.W., Stern, M.B. and Sethi, K. (2009) The scientific and clinical basis for the treatment of Parkinson disease. Neurology 72(21 Suppl 4): S1-136.

Schapira, A.H.V., Emrebe, M., Jenner, P., and Poewe, W. (2009) Levodopa in the treatment of Parkinson's disease. European Journal of Neurology 16: 982–989.

Khora, S.-P. and Hsub, A. (2007) The Pharmacokinetics and Pharmacodynamics of Levodopa in the Treatment of Parkinson’s Disease. Current Clinical Pharmacology 2: 234-243.

Chen, J.J. and Swope, D.M. (2007) Pharmacotherapy for Parkinson's Disease. Pharmacotherapy 27(12 Pt 2): 161S–173S.

FDA Approved Labeling Text for NDA 021264 Dated 7/20/10; NDC code: 15054-0211-5; http://labels.fda.gov/packagecode.cfm.

http://www.vectura.com/news/releases/2010/2010-11-16a.aspx; 2010.

Http://www.britannia-pharm.co.uk/news.html; 2009.

Espay, A.J. (2010) Management of motor complications in Parkinson disease: current and emerging therapies. Neurologic Clinics 28(4): 913-25.

Medacorp report. (Dec 2011) Trends in the treatment of Parkinson's disease prepared for Cynapsus Therapeutics.

Published

2012-07-01

Issue

Section

Case Study