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Formulating propranolol as an amorphous melt affords reduced skin irritation potential for transdermal drug delivery

Kazuhiro Aoyagi

Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, USA.

Development Department, Medical Division, Nitto Denko Corporation, Osaki, Miyagi 989-6493, Japan.

K.A. and M.Z. contributed equally and are co-first authors.

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Michael Zakrewsky

Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, USA.

Center for Bioengineering, University of California, Santa Barbara, CA 93106, USA.

K.A. and M.Z. contributed equally and are co-first authors.

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, and

Samir Mitragotri

Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, USA.

Center for Bioengineering, University of California, Santa Barbara, CA 93106, USA.

E-mail Address: samir@engineering.ucsb.edu

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https://doi.org/10.1142/S2339547815500107Cited by:2 (Source: Crossref)

Abstract

Oral propranolol is commonly the first-line treatment of infantile hemangioma. However, oral delivery of propranolol is limited by systemic side effects, particularly in infants. Topical application may be a more patient friendly alternative while concurrently affording targeted delivery to the site of the skin lesion. Unfortunately, dose-dependent skin irritation is typically observed when propranolol is applied topically. Of additional concern, irritation is often exacerbated by organic solvents required to formulate propranolol. To address these concerns, we present novel formulations of propranolol as amorphous melts. Propranolol melts were successfully synthesized, and their physicochemical properties were tuned suitably for transdermal delivery using dialkyl sulfosuccinates as the counter species. Melts used in this study possessed the ability to penetrate skin when applied neat, without the need of any addition of solvent. Moreover, skin irritation potential of the lead melt was reduced compared to that of the propranolol free base (PFB). This reduction may be due to association of propranolol with the counter species in amorphous melts. The results presented here suggest amorphous melt formulations may open up the possibility to topically deliver drugs that traditionally elicit skin irritation.

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