Mayank Kumar Singh1, Deep Pooja2, Halley Gora Ravuri3, Anusha Gunukula3, Hitesh Kulhari4, Ramakrishna Sistla5. 1. Pharmacology & Toxicology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhavan, New Delhi 1100001, India. 2. IICT-RMIT Joint Research Centre, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India. 3. Pharmacology & Toxicology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India. 4. School of Nano Sciences, Central University of Gujarat, Gandhinagar, Gujarat 382 030, India. Electronic address: hitesh.kulhari@cug.ac.in. 5. Pharmacology & Toxicology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhavan, New Delhi 1100001, India. Electronic address: sistla@iict.res.in.
Abstract
BACKGROUND: Nanosuspension is a biphasic system consisting of native drug particles dispersed in an aqueous surfactant or polymeric solution with a particle size between 10 to 1000 nm. In contrast to other drug delivery systems, nanosuspension offer the unique advantage of increasing solubility of the native drug resulting into faster drug absorption and hence achieving faster maximum plasma concentration. HYPOTHESIS/ PURPOSE: The present study aims to evaluate surfactants/polymer stabilized nanosuspensions of naringenin (NN), a phytomedicine, to surpass its poor physiochemical properties and low oral bioavailability. STUDY DESIGN: Optimization and characterization (DLS, SEM, PXRD and DSC) of nanosuspensions followed by in-vitro drug dissolution studies and pharmacokinetic study in male Sprague-Dawley rats were performed. METHODS: Nanosuspensions were prepared by precipitation-ultrasonication method with varying concentrations of different surfactants and polymer such as sodium cholate (SC), sodium lauryl sulphate (SLS), poly ethylene glycol 4000 (PEG), polysorbate 80 (Tween® 80), poloxomer-188 and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS or Vitamin E-TPGS). RESULTS: Nanosuspension prepared with 0.5% w/v d-α-Tocopherol polyethylene glycol 1000 succinate (TPNS) and 7.5 mg NN, showed the smallest size of 118.1 ± 2.7 nm. TPNS showed increase in drug dissolution in simulated gastric fluid pH 1.2 (SGF) and phosphate buffer pH 6.8 (PB). TPNS demonstrated an improved pharmacokinetic profile compared to pure NN resulting 2.14 and 3.76 folds increase in Cmax and AUC, respectively. In addition, TPNS were stable over a period of six months. CONCLUSION: The developed formulation strategy of nanosuspension could be exploited to improve the solubility and bio-availability of poorly soluble NN and other phytomedicines.
BACKGROUND: Nanosuspension is a biphasic system consisting of native drug particles dispersed in an aqueous surfactant or polymeric solution with a particle size between 10 to 1000 nm. In contrast to other drug delivery systems, nanosuspension offer the unique advantage of increasing solubility of the native drug resulting into faster drug absorption and hence achieving faster maximum plasma concentration. HYPOTHESIS/ PURPOSE: The present study aims to evaluate surfactants/polymer stabilized nanosuspensions of naringenin (NN), a phytomedicine, to surpass its poor physiochemical properties and low oral bioavailability. STUDY DESIGN: Optimization and characterization (DLS, SEM, PXRD and DSC) of nanosuspensions followed by in-vitro drug dissolution studies and pharmacokinetic study in male Sprague-Dawley rats were performed. METHODS: Nanosuspensions were prepared by precipitation-ultrasonication method with varying concentrations of different surfactants and polymer such as sodium cholate (SC), sodium lauryl sulphate (SLS), poly ethylene glycol 4000 (PEG), polysorbate 80 (Tween® 80), poloxomer-188 and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS or Vitamin E-TPGS). RESULTS: Nanosuspension prepared with 0.5% w/v d-α-Tocopherol polyethylene glycol 1000 succinate (TPNS) and 7.5 mg NN, showed the smallest size of 118.1 ± 2.7 nm. TPNS showed increase in drug dissolution in simulated gastric fluid pH 1.2 (SGF) and phosphate buffer pH 6.8 (PB). TPNS demonstrated an improved pharmacokinetic profile compared to pure NN resulting 2.14 and 3.76 folds increase in Cmax and AUC, respectively. In addition, TPNS were stable over a period of six months. CONCLUSION: The developed formulation strategy of nanosuspension could be exploited to improve the solubility and bio-availability of poorly soluble NN and other phytomedicines.