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Pharmacokinetic and pharmacodynamic studies of nisoldipine-loaded solid lipid nanoparticles developed by central composite design.
Drug Dev Ind Pharm. 2015; 41(12):1968-77.DD

Abstract

OBJECTIVE

Nisoldipine (ND) is a potential antihypertensive drug with low oral bioavailability. The aim was to develop an optimal formulation of ND-loaded solid lipid nanoparticles (ND-SLNs) for improved oral bioavailability and pharmacodynamic effect by using a two-factor, three-level central composite design. Glyceryl trimyristate (Dynasan 114) and egg lecithin were selected as independent variables. Particle size (Y1), PDI (Y2) and entrapment efficiency (EE) (Y3) of SLNs were selected as dependent response variables.

METHODS

The ND-SLNs were prepared by hot homogenization followed by ultrasonication. The size, PDI, zeta potential, EE, assay, in vitro release and morphology of ND-SLNs were characterized. Further, the pharmacokinetic (PK) and pharmacodynamic behavior of ND-SLNs was evaluated in male Wistar rats.

RESULTS

The optimal ND-SLN formulation had particle size of 104.4 ± 2.13 nm, PDI of 0.241 ± 0.02 and EE of 89.84 ± 0.52%. The differential scanning calorimetry and X-ray diffraction analyses indicated that the drug incorporated into ND-SLNs was in amorphous form. The morphology of ND-SLNs was found to be nearly spherical by scanning electron microscopy. The optimized formulation was stable at refrigerated and room temperature for 3 months. PK studies showed that 2.17-fold increase in oral bioavailability when compared with a drug suspension. In pharmacodynamic studies, a significant reduction in the systolic blood pressure was observed, which sustained for a period of 36 h when compared with a controlled suspension.

CONCLUSION

Taken together, the results conclusively demonstrated that the developed optimal ND-SLNs caused significant enhancement in oral bioavailability along with pharmacodynamic effect.

Authors+Show Affiliations

a Department of Pharmaceutical Sciences , Laboratory of Nanotechnology, University College of Pharmaceutical Sciences, Kakatiya University , Warangal , Telangana , India.a Department of Pharmaceutical Sciences , Laboratory of Nanotechnology, University College of Pharmaceutical Sciences, Kakatiya University , Warangal , Telangana , India.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25830370

Citation

Dudhipala, Narendar, and Kishan Veerabrahma. "Pharmacokinetic and Pharmacodynamic Studies of Nisoldipine-loaded Solid Lipid Nanoparticles Developed By Central Composite Design." Drug Development and Industrial Pharmacy, vol. 41, no. 12, 2015, pp. 1968-77.
Dudhipala N, Veerabrahma K. Pharmacokinetic and pharmacodynamic studies of nisoldipine-loaded solid lipid nanoparticles developed by central composite design. Drug Dev Ind Pharm. 2015;41(12):1968-77.
Dudhipala, N., & Veerabrahma, K. (2015). Pharmacokinetic and pharmacodynamic studies of nisoldipine-loaded solid lipid nanoparticles developed by central composite design. Drug Development and Industrial Pharmacy, 41(12), 1968-77. https://doi.org/10.3109/03639045.2015.1024685
Dudhipala N, Veerabrahma K. Pharmacokinetic and Pharmacodynamic Studies of Nisoldipine-loaded Solid Lipid Nanoparticles Developed By Central Composite Design. Drug Dev Ind Pharm. 2015;41(12):1968-77. PubMed PMID: 25830370.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetic and pharmacodynamic studies of nisoldipine-loaded solid lipid nanoparticles developed by central composite design. AU - Dudhipala,Narendar, AU - Veerabrahma,Kishan, Y1 - 2015/04/01/ PY - 2015/4/2/entrez PY - 2015/4/2/pubmed PY - 2016/8/19/medline KW - Central composite design KW - nisoldipine KW - pharmacodynamics KW - pharmacokinetics KW - solid lipid nanoparticles SP - 1968 EP - 77 JF - Drug development and industrial pharmacy JO - Drug Dev Ind Pharm VL - 41 IS - 12 N2 - OBJECTIVE: Nisoldipine (ND) is a potential antihypertensive drug with low oral bioavailability. The aim was to develop an optimal formulation of ND-loaded solid lipid nanoparticles (ND-SLNs) for improved oral bioavailability and pharmacodynamic effect by using a two-factor, three-level central composite design. Glyceryl trimyristate (Dynasan 114) and egg lecithin were selected as independent variables. Particle size (Y1), PDI (Y2) and entrapment efficiency (EE) (Y3) of SLNs were selected as dependent response variables. METHODS: The ND-SLNs were prepared by hot homogenization followed by ultrasonication. The size, PDI, zeta potential, EE, assay, in vitro release and morphology of ND-SLNs were characterized. Further, the pharmacokinetic (PK) and pharmacodynamic behavior of ND-SLNs was evaluated in male Wistar rats. RESULTS: The optimal ND-SLN formulation had particle size of 104.4 ± 2.13 nm, PDI of 0.241 ± 0.02 and EE of 89.84 ± 0.52%. The differential scanning calorimetry and X-ray diffraction analyses indicated that the drug incorporated into ND-SLNs was in amorphous form. The morphology of ND-SLNs was found to be nearly spherical by scanning electron microscopy. The optimized formulation was stable at refrigerated and room temperature for 3 months. PK studies showed that 2.17-fold increase in oral bioavailability when compared with a drug suspension. In pharmacodynamic studies, a significant reduction in the systolic blood pressure was observed, which sustained for a period of 36 h when compared with a controlled suspension. CONCLUSION: Taken together, the results conclusively demonstrated that the developed optimal ND-SLNs caused significant enhancement in oral bioavailability along with pharmacodynamic effect. SN - 1520-5762 UR - https://www.unboundmedicine.com/medline/citation/25830370/Pharmacokinetic_and_pharmacodynamic_studies_of_nisoldipine_loaded_solid_lipid_nanoparticles_developed_by_central_composite_design_ L2 - http://www.tandfonline.com/doi/full/10.3109/03639045.2015.1024685 DB - PRIME DP - Unbound Medicine ER -