Therapeutic efficacy of many marketed and investigational drug molecules is significantly affected due to their poor aqueous solubility. Search for new drug molecules with improved solubility is time consuming and costly procedure. An attractive and profitable alternative to this approach is finding excipients which can act as solubility enhancers for currently existing poorly soluble drugs. In this study, the derivative of oleic acid and high molecular weight polyethylene glycol monomethyl ether was explored as a solubility enhancer for poorly soluble drugs by taking furosemide, a BCS class IV drug as a model.
Oleic acid (OA) and polyethylene glycol monomethyl ether of molecular weight 5000 (mPEG5000) were reacted at 170 oC for 5 h to obtain OA-mPEG5000. Synthesized OA-mPEG5000 was evaluated for its applicability as a solubilizer and nanocarrier of furosemide by preparing polymersomes. The solubility of furosemide in water and aqueous OA-mPEG5000 solution was determined using shake flask method. Size, polydispersity index (PI) and zeta potential (ZP) were determined by dynamic light scattering technique using a Zetasizer Nano ZS90 (Malvern Instruments, UK). Percentage encapsulation efficiency (%EE) was determined by the ultrafiltration method using Amicon® Ultra-0.5 centrifugal filter tubes (Millipore Corp., USA) of 10 kDa pore size. In vitro drug release study was performed using dialysis method.
Solubility of furosemide in OA-mPEG5000 (1% w/w) and water was 3.40±0.25 mg/ml and 1.02±0.04 mg/ml respectively at 37 oC. At 25 oC, there was a 3-fold increase in solubilization of furosemide in OA-mPEG5000 (1% w/w) (0.027±0.001 mg/ml) compared to water (0.09±0.001 mg/ml). Size, polydispersity index and zeta potential of polymersomes ranged from 40 to 145.5 nm, 0.187 to 0.511 and -4.0 to -12.77 mV respectively. %EE for all formulations was > 95% indicating higher degree of encapsulation of furosemide in the core of polymersomes. Drug release study revealed a burst release (71%) in initial 1 h.
Significant enhancement in solubility of furosemide and formation of polymersomes with high drug encapsulation suggested that OA-mPEG5000 could be a good solubilizer and nanocarrier for poorly soluble drugs.
Pradeep Kumar Bolla– Student, University of Texas at El Paso, El Paso, Texas
Chandra Sekhar Kolli– Associate Professor, California Health Sciences University
Jwala Renukuntla– Assistant Professor, University of Texas at El Paso, El Paso, Texas