Liquid salts could make topical drugs more effective, safe

Formulating drugs as liquid salts may help reduce the toxicity of some topical drugs, while also making them more effective, scientists including one of Indian-origin have found.
Researchers from the University of California, Santa Barbara (UCSB) in US has demonstrated a novel formulation of propranolol as a liquid salt which enables delivery through skin with reduced toxicity.
Skin toxicity remains a major challenge in the design and use of new topical drug formulations.
Many drugs must be dissolved in organic solvents which are typically toxic to the skin. In addition, many drugs such as propranolol itself show dose-dependent skin toxicity.

Formulating drugs as liquid salt mitigates both sources of toxicity. Given their fluid nature, liquid salts eliminate the necessity of organic solvents.
In addition, counter ions used to form the liquid salts shield the drug 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 study senior author Samir Mitragotri, from UCSB.
Previous studies have shown how liquid salts may enhance drug transport through the skin; however, this is the first study that reports the design of liquid salts to minimise skin toxicity.

Such formulations can increase the spectrum of drugs that can be safely delivered via a transdermal patch.
"An ideal drug liquid salt would need to permeate through the skin as an associated ion pair. Eventually, however, the drug and the counter ion must dissociate in blood to preserve drug's therapeutic efficacy," said co-first author Michael Zakrewsky.
"We show that these attributes can be balanced through careful selection of counter ions," said Zakrewsky.
"This technology presents an exciting new, patient compliant solution for treating diseases," he said.
The research was published in the journal Technology.