Abstract
PURPOSE
Zaleplon (ZL) is a hypnotic drug prescribed for the management of insomnia and convulsions. The oral bioavailability of ZL was low (∼30%) owing to poor water solubility and hepatic first-pass metabolism. The cornerstone of this investigation is to develop and optimize solid lipid nanoparticles (SLNs) of ZL with the aid of Box-Behnken design (BBD) to improve the oral bioavailability.
METHODS
A design space with three formulation variables at three levels were evaluated in BBD. Amount of lipid (A1), amount of surfactant (A2) and concentration of co-surfactant (%) (A3) were selected as independent variables, whereas, particle size (B1), entrapment efficiency (B2) and zeta potential (ZP, B3) as responses. ZL-SLNs were prepared by hot homogenization with ultrasonication method and evaluated for responses to obtain optimized formulation. Morphology of nanoparticles was observed under SEM. DSC and XRD studies were examined to understand the native crystalline behavior of drug in SLN formulations. Further, in vivo studies were performed in Wistar rats.
RESULTS
The optimized formulation with 132.89 mg of lipid, 106.7 mg of surfactant and 0.2% w/v of co-surfactant ensued in the nanoparticles with 219.9 ± 3.7 nm of size, -25.66 ± 2.83 mV surface charge and 86.83 ± 2.65% of entrapment efficiency. SEM studies confirmed the spherical shape of SLN formulations. The DSC and XRD studies revealed the transformation of crystalline drug to amorphous form in SLN formulation. In conclusion, in vivo studies in male Wistar rats demonstrated an improvement in the oral bioavailability of ZL from SLN over control ZL suspension.
CONCLUSIONS
The enhancement in the oral bioavailability of ZL from SLNs, developed with the aid of BBD, explicated the potential of lipid-based nanoparticles as a potential carrier in improving the oral delivery of this poorly soluble drug.
TY - JOUR
T1 - Lipid nanoparticles of zaleplon for improved oral delivery by Box-Behnken design: optimization, in vitro and in vivo evaluation.
AU - Dudhipala,Narendar,
AU - Janga,Karthik Yadav,
Y1 - 2017/03/26/
PY - 2017/3/10/pubmed
PY - 2017/9/14/medline
PY - 2017/3/10/entrez
KW - Box–Behnken design
KW - DSC
KW - XRD
KW - Zaleplon
KW - bioavailability
KW - entrapment efficiency
KW - independent variables
KW - size
SP - 1205
EP - 1214
JF - Drug development and industrial pharmacy
JO - Drug Dev Ind Pharm
VL - 43
IS - 7
N2 - PURPOSE: Zaleplon (ZL) is a hypnotic drug prescribed for the management of insomnia and convulsions. The oral bioavailability of ZL was low (∼30%) owing to poor water solubility and hepatic first-pass metabolism. The cornerstone of this investigation is to develop and optimize solid lipid nanoparticles (SLNs) of ZL with the aid of Box-Behnken design (BBD) to improve the oral bioavailability. METHODS: A design space with three formulation variables at three levels were evaluated in BBD. Amount of lipid (A1), amount of surfactant (A2) and concentration of co-surfactant (%) (A3) were selected as independent variables, whereas, particle size (B1), entrapment efficiency (B2) and zeta potential (ZP, B3) as responses. ZL-SLNs were prepared by hot homogenization with ultrasonication method and evaluated for responses to obtain optimized formulation. Morphology of nanoparticles was observed under SEM. DSC and XRD studies were examined to understand the native crystalline behavior of drug in SLN formulations. Further, in vivo studies were performed in Wistar rats. RESULTS: The optimized formulation with 132.89 mg of lipid, 106.7 mg of surfactant and 0.2% w/v of co-surfactant ensued in the nanoparticles with 219.9 ± 3.7 nm of size, -25.66 ± 2.83 mV surface charge and 86.83 ± 2.65% of entrapment efficiency. SEM studies confirmed the spherical shape of SLN formulations. The DSC and XRD studies revealed the transformation of crystalline drug to amorphous form in SLN formulation. In conclusion, in vivo studies in male Wistar rats demonstrated an improvement in the oral bioavailability of ZL from SLN over control ZL suspension. CONCLUSIONS: The enhancement in the oral bioavailability of ZL from SLNs, developed with the aid of BBD, explicated the potential of lipid-based nanoparticles as a potential carrier in improving the oral delivery of this poorly soluble drug.
SN - 1520-5762
UR - https://www.unboundmedicine.com/medline/citation/28274147/Lipid_nanoparticles_of_zaleplon_for_improved_oral_delivery_by_Box_Behnken_design:_optimization_in_vitro_and_in_vivo_evaluation_
L2 - https://www.tandfonline.com/doi/full/10.1080/03639045.2017.1304957
DB - PRIME
DP - Unbound Medicine
ER -
