Evaluation of Oleic Acid and Polyethylene Glycol Monomethyl Ether Conjugate (PEGylated Oleic Acid) as a Solubility Enhancer of Furosemide

Processes

PradeepKumar Bolla¹  SaiHS. Boddu²  Jwala Renukuntla³  RahulS. Kalhapure⁴ 

[1] Department of Biomedical Engineering, College of Engineering, The University of Texas at El Paso, 500 W University Ave, El Paso, TX 79968, USA;Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman 2758, UAE;Department of Pharmaceutical Sciences, School of Pharmacy, High Point University, High Point, NC 27240, USA;School of Pharmacy, The University of Texas at El Paso, 1101 N Campbell St, El Paso, TX 79902, USA;

关键词: oleic acid;    mPEG;    furosemide;    OA-mPEG₅₀₀₀;    solubility;    polymersomes;    BCS class IV;    PEGylated oleic acid;   

DOI  :  10.3390/pr7080520

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown