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Liquid Salts Deliver Drugs Through the Skin

Discovery may improve safety of transdermal patches

Formulating drugs as liquid salts may provide a safe and efficient strategy for topical delivery of drugs that cause skin toxicity, according to researchers at the University of California, Santa Barbara. The investigators have demonstrated a new formulation of propranolol as a liquid salt, which allows delivery of the drug through the skin with reduced toxicity. The report was published in the December 2015 issue of Technology.

Skin toxicity remains a major challenge in the design and use of new topical drug formulations, according to the authors. Many drugs must be dissolved in organic solvents, which are typically toxic to the skin. In addition, some drugs, such as propranolol, show dose-dependent skin toxicity. Formulating medications as liquids mitigates both sources of toxicity, the authors say. In addition, ions used to form the liquid salts shield the drug’s charge, which further reduces drug-induced toxicity.

“Propranolol is positively charged, which is a likely source of its toxicity. Shielding of this charge by association with a counter-species in the liquid salt reduces its toxicity. These findings are broadly applicable to many charged drugs,” said senior author Samir Mitragotri, PhD.

Previous reports have shown how liquid salts enhance drug transport through the skin, but the new study is the first to describe the design of liquid salts to minimize skin toxicity. Such formulations increase the spectrum of drugs that can be safely delivered via a transdermal patch, according to the authors.

“An ideal drug liquid salt would need to permeate through the skin as an associated ion pair,” said Dr. Michael Zakrewsky, the paper’s co-first author. “Eventually, however, the drug and the counter-ion must dissociate in blood to preserve the drug’s therapeutic efficacy. We show that these attributes can be balanced through careful selection of counter-ions. This technology presents an exciting, new, patient-compliant solution for treating diseases.”

Source: World Scientific Publishers; December 28, 2015.

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