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Lipid nanoparticles for transdermal delivery of flurbiprofen: formulation, in vitro, ex vivo and in vivo studies.

Bhaskar K, Anbu J, Ravichandiran V, Venkateswarlu V, Rao YM - Lipids Health Dis (2009)

Bottom Line: The Cmax of the B1 formulation was 38.67 +/- 2.77 microg/ml, which was significantly higher than the A1 formulation (Cmax = 21.79 +/- 2.96 microg/ml).The bioavailability of flurbiprofen with reference to oral administration was found to increase by 4.4 times when gel formulations were applied.Both the SLN and NLC dispersions and gels enriched with SLN and NLC possessed a sustained drug release over period of 24 h but the sustained effect was more pronounced with the SLN and NLC gel.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, VELS University, Velan Nagar, Pallavaram, Chennai, Tamil Nadu, India. bhaskurra@yahoo.com

ABSTRACT
The aim of the study is to prepare aqueous dispersions of lipid nanoparticles--flurbiprofen solid lipid nanoparticles (FLUSLN) and flurbiprofen nanostructured lipid carriers (FLUNLC) by hot homogenization followed by sonication technique and then incorporated into the freshly prepared hydrogels for transdermal delivery. They are characterized for particle size, for all the formulations, more than 50% of the particles were below 300 nm after 90 days of storage at RT. DSC analyses were performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by TEM which revealed fairly spherical shape of the formulations. Further they were evaluated for in vitro drug release characteristics, rheological behaviour, pharmacokinetic and pharmacodynamic studies. The pharmacokinetics of flurbiprofen in rats following application of SLN gel (A1) and NLC gel (B1) for 24 h were evaluated. The Cmax of the B1 formulation was 38.67 +/- 2.77 microg/ml, which was significantly higher than the A1 formulation (Cmax = 21.79 +/- 2.96 microg/ml). The Cmax and AUC of the B1 formulation were 1.8 and 2.5 times higher than the A1 gel formulation respectively. The bioavailability of flurbiprofen with reference to oral administration was found to increase by 4.4 times when gel formulations were applied. Anti-inflammatory effect in the Carrageenan-induced paw edema in rat was significantly higher for B1 and A1 formulation than the orally administered flurbiprofen. Both the SLN and NLC dispersions and gels enriched with SLN and NLC possessed a sustained drug release over period of 24 h but the sustained effect was more pronounced with the SLN and NLC gel.

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DSC thermograms of flurbiprofen (A), trimyristin (B), physical mixture of flurbiprofen and trimyristin (C) lyophilized flurbiprofen NLC (D) and captex 355 (E).
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Figure 4: DSC thermograms of flurbiprofen (A), trimyristin (B), physical mixture of flurbiprofen and trimyristin (C) lyophilized flurbiprofen NLC (D) and captex 355 (E).

Mentions: Figures 3 and 4 shows DSC curves of flurbiprofen (FLU), trimyristin (TM), physical mixture (PM), lyophilized FLUSLN and lyophilized FLUNLC respectively. The thermograms of the lyophilized FLUSLN and FLUNLC did not show the melting peak for the flurbiprofen around 117°C. This shows that flurbiprofen was not in crystalline state but it is in amorphous state. Endothermic peak of glucose used as cryoprotectant was observed at 148.5°C in FLUSLN and FLUNLC curve. Similar results were reported by Cavalli et al. 1997, stating that rapid quenching of the microemulsion does not allow the drug to crystallize [12]. DSC analysis of camptothecin SLN prepared by high pressure homogenization showed that camptothecin was in amorphous state [13]. In our method, lipids and flurbiprofen were dissolved in a mixture of solvents and subsequently, solvents were evaporated. This allowed homogeneous dispersion of drug in the lipid. Furthermore, method of preparation (homogenization followed by ultrasonication) and the presence of surfactants do not allow the drug to crystallize. Thermodynamic stability of lipid nanoparticles depends upon their existing lipid modification. Polymorphic transitions after crystallization of triglyceride nanoparticles are slower for longer chain triglycerides than for shorter chain triglycerides, whereas these transitions are faster for small size of crystallites. The type of surfactant and storage time affects the crystallinity of SLN/NLC and, consequently, degradation velocity [14]. Melting points of lyophilized SLN and NLC were found to be 56.25°C and 57.25°C respectively.


Lipid nanoparticles for transdermal delivery of flurbiprofen: formulation, in vitro, ex vivo and in vivo studies.

Bhaskar K, Anbu J, Ravichandiran V, Venkateswarlu V, Rao YM - Lipids Health Dis (2009)

DSC thermograms of flurbiprofen (A), trimyristin (B), physical mixture of flurbiprofen and trimyristin (C) lyophilized flurbiprofen NLC (D) and captex 355 (E).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651881&req=5

Figure 4: DSC thermograms of flurbiprofen (A), trimyristin (B), physical mixture of flurbiprofen and trimyristin (C) lyophilized flurbiprofen NLC (D) and captex 355 (E).
Mentions: Figures 3 and 4 shows DSC curves of flurbiprofen (FLU), trimyristin (TM), physical mixture (PM), lyophilized FLUSLN and lyophilized FLUNLC respectively. The thermograms of the lyophilized FLUSLN and FLUNLC did not show the melting peak for the flurbiprofen around 117°C. This shows that flurbiprofen was not in crystalline state but it is in amorphous state. Endothermic peak of glucose used as cryoprotectant was observed at 148.5°C in FLUSLN and FLUNLC curve. Similar results were reported by Cavalli et al. 1997, stating that rapid quenching of the microemulsion does not allow the drug to crystallize [12]. DSC analysis of camptothecin SLN prepared by high pressure homogenization showed that camptothecin was in amorphous state [13]. In our method, lipids and flurbiprofen were dissolved in a mixture of solvents and subsequently, solvents were evaporated. This allowed homogeneous dispersion of drug in the lipid. Furthermore, method of preparation (homogenization followed by ultrasonication) and the presence of surfactants do not allow the drug to crystallize. Thermodynamic stability of lipid nanoparticles depends upon their existing lipid modification. Polymorphic transitions after crystallization of triglyceride nanoparticles are slower for longer chain triglycerides than for shorter chain triglycerides, whereas these transitions are faster for small size of crystallites. The type of surfactant and storage time affects the crystallinity of SLN/NLC and, consequently, degradation velocity [14]. Melting points of lyophilized SLN and NLC were found to be 56.25°C and 57.25°C respectively.

Bottom Line: The Cmax of the B1 formulation was 38.67 +/- 2.77 microg/ml, which was significantly higher than the A1 formulation (Cmax = 21.79 +/- 2.96 microg/ml).The bioavailability of flurbiprofen with reference to oral administration was found to increase by 4.4 times when gel formulations were applied.Both the SLN and NLC dispersions and gels enriched with SLN and NLC possessed a sustained drug release over period of 24 h but the sustained effect was more pronounced with the SLN and NLC gel.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, VELS University, Velan Nagar, Pallavaram, Chennai, Tamil Nadu, India. bhaskurra@yahoo.com

ABSTRACT
The aim of the study is to prepare aqueous dispersions of lipid nanoparticles--flurbiprofen solid lipid nanoparticles (FLUSLN) and flurbiprofen nanostructured lipid carriers (FLUNLC) by hot homogenization followed by sonication technique and then incorporated into the freshly prepared hydrogels for transdermal delivery. They are characterized for particle size, for all the formulations, more than 50% of the particles were below 300 nm after 90 days of storage at RT. DSC analyses were performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by TEM which revealed fairly spherical shape of the formulations. Further they were evaluated for in vitro drug release characteristics, rheological behaviour, pharmacokinetic and pharmacodynamic studies. The pharmacokinetics of flurbiprofen in rats following application of SLN gel (A1) and NLC gel (B1) for 24 h were evaluated. The Cmax of the B1 formulation was 38.67 +/- 2.77 microg/ml, which was significantly higher than the A1 formulation (Cmax = 21.79 +/- 2.96 microg/ml). The Cmax and AUC of the B1 formulation were 1.8 and 2.5 times higher than the A1 gel formulation respectively. The bioavailability of flurbiprofen with reference to oral administration was found to increase by 4.4 times when gel formulations were applied. Anti-inflammatory effect in the Carrageenan-induced paw edema in rat was significantly higher for B1 and A1 formulation than the orally administered flurbiprofen. Both the SLN and NLC dispersions and gels enriched with SLN and NLC possessed a sustained drug release over period of 24 h but the sustained effect was more pronounced with the SLN and NLC gel.

Show MeSH
Related in: MedlinePlus