Abstract
Poor aqueous solubility limits the therapeutic efficacy of many marketed and investigational drugs. Synthesis of new drugs with improved solubility is challenging due to time constraint and expenses involved. Therefore, finding the solubility enhancers for existing drugs is an attractive and profitable strategy. In this study, PEGylated oleic acid (OA-mPEG5000), a conjugate of oleic acid and mPEG5000 was synthesized and evaluated as a solubilizer for furosemide. OA-mPEG5000 was evaluated as a nanocarrier for furosemide by formulating polymersomes. Solubility of furosemide in milli-Q water and aqueous OA-mPEG5000 solution was determined using shake flask method. At 37 °C, the solubility of furosemide in OA-mPEG5000 (1% w/w) and milli-Q water was 3404.7 ± 254.6 µg/mL and 1020.2 ± 40.9 µg/mL, respectively. Results showed there was a 3.34-fold increase in solubility of furosemide in OA-mPEG5000 compared to water at 37 °C. At 25 °C, there was a 3.31-fold increase in solubilization of furosemide in OA-mPEG5000 (1% w/w) (90.0 ± 1.45 µg/mL) compared to milli-Q water (27.2 ± 1.43 µg/mL). Size, polydispersity index and zeta potential of polymersomes ranged from 85–145.5 nm, 0.187–0.511 and −4.0–12.77 mV, respectively. In-vitro release study revealed a burst release (71%) within 1 h. Significant enhancement in solubility and formation of polymersomes suggested that OA-mPEG5000 could be a good solubilizer and nanocarrier for furosemide.
Highlights
All active pharmaceutical ingredients (APIs) irrespective of the mode of drug administration should have at least limited aqueous solubility for therapeutic efficacy as water is the major component in all body fluids [1]
Poor aqueous solubility of APIs leads to suboptimal patient outcomes due to poor oral bioavailability and variable pharmacokinetics [2,3,4]
Furosemide solubility was significantly higher at both OA-mPEG5000 (1% w/w) and milli-Q water
Summary
All active pharmaceutical ingredients (APIs) irrespective of the mode of drug administration should have at least limited aqueous solubility for therapeutic efficacy as water is the major component in all body fluids [1]. Poor aqueous solubility of APIs leads to suboptimal patient outcomes due to poor oral bioavailability and variable pharmacokinetics [2,3,4]. The maximum amount of a substance that will dissolve in a given amount of solvent at a specified temperature is known as solubility and is a characteristic property of a specific solute–solvent combination [2,5,6]. Each API differs in terms of solubility profile [1,5]. 40% of drugs in the market and about 90% of molecules in the discovery pipeline have poor water solubility [7,8].
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