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Lipid nanoparticles of zaleplon for improved oral delivery by Box-Behnken design: optimization, in vitro and in vivo evaluation.
Drug Dev Ind Pharm. 2017 Jul; 43(7):1205-1214.DD

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.

Authors+Show Affiliations

a Nanotechnology Laboratory, Vaagdevi College of Pharmaceutical Sciences , Warangal , India.b Department of Pharmaceutics and Drug Delivery , School of Pharmacy, University of Mississippi , MS , USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28274147

Citation

Dudhipala, Narendar, and Karthik Yadav Janga. "Lipid Nanoparticles of Zaleplon for Improved Oral Delivery By Box-Behnken Design: Optimization, in Vitro and in Vivo Evaluation." Drug Development and Industrial Pharmacy, vol. 43, no. 7, 2017, pp. 1205-1214.
Dudhipala N, Janga KY. Lipid nanoparticles of zaleplon for improved oral delivery by Box-Behnken design: optimization, in vitro and in vivo evaluation. Drug Dev Ind Pharm. 2017;43(7):1205-1214.
Dudhipala, N., & Janga, K. Y. (2017). Lipid nanoparticles of zaleplon for improved oral delivery by Box-Behnken design: optimization, in vitro and in vivo evaluation. Drug Development and Industrial Pharmacy, 43(7), 1205-1214. https://doi.org/10.1080/03639045.2017.1304957
Dudhipala N, Janga KY. Lipid Nanoparticles of Zaleplon for Improved Oral Delivery By Box-Behnken Design: Optimization, in Vitro and in Vivo Evaluation. Drug Dev Ind Pharm. 2017;43(7):1205-1214. PubMed PMID: 28274147.
* Article titles in AMA citation format should be in sentence-case
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 - http://www.tandfonline.com/doi/full/10.1080/03639045.2017.1304957 DB - PRIME DP - Unbound Medicine ER -