Formulation, characterization and in vitro-in vivo evaluation of flurbiprofen-loaded nanostructured lipid carriers for transdermal delivery.

Flurbiprofen is used in the treatment of arthritis. However, its multiple dosing due to short elimination half life is a concern for such treatment. This work aims to develop nanostructured lipid carriers (NLCs) of flurbiprofen and evaluate their potential for transdermal delivery. The NLCs were prepared by the optimized o/w emulsification-homogenization-sonication technique using coconut oil (liquid lipid). The NLCs were found to be spherical with uniform size (214 nm). The entrapment efficiency and zeta potential were 92.58% and -30.70 mV, respectively. Differential scanning calorimetry (DSC) showed the amorphous state of flurbiprofen encapsulated in NLCs. The percentage cumulative drug release through the excised rat skin from NLCs was biphasic and significantly prolonged compared with the commercial gel. DSC of the treated skin indicated that the NLCs penetrate into follicles of the skin and accumulate in the dermis. The bioavailability of flurbiprofen from NLCs was more than 1.7-fold that of the commercial gel. The NLCs showed a quick onset and sustained anti-inflammatory effect over period of 24 h for carrageenan-induced rat paw edema than the commercial gel. The stability data revealed that the NLCs were more stable when stored at 5°C. In conclusion, prepared NLCs have potential for skin targeting and sustained drug release.

Formulation and evaluation of flurbiprofen-loaded genipin cross-linked gelatin microspheres for intra-articular delivery.

Oral and parenteral formulations are challenging to produce therapeutic concentration of flurbiprofen in the joints. This encourages for the development of formulation for long term drug retention in the joint through intra-articular (i. a.) administration. In this study, genipin cross-linked gelatin microspheres of flurbiprofen were prepared for i. a. delivery. The microspheres were prepared using emulsification-homogenization-cross-linking method by changing the experimental variables such as concentration of cross-linker, cross-linking time and cross-linking temperature. The microspheres showed drug entrapment up to 76.19% with a mean particle size range of 5.91-8.19 µm. The degree of cross-linking and water-soluble fraction were 8.27-59.33% and 12.29-81.23%, respectively. SEM confirmed smooth surface and spherical shape of the microspheres. FTIR and (13)C-NMR confirmed cross-linking of gelatin by genipin. No chemical change in encapsulated drug was observed by FTIR and TGA. DSC and XRD indicated the molecular dispersion of drug within microspheres. Optimized microspheres could prolong the drug release for more than 108 h with anomalous transport. Histopathology confirmed the biocompatibility of microspheres in the rat (Wistar) knee joint. After 96 h of i. a. injection, significant higher amount (42.56%) of administered drug in cross-linked microspheres was recovered than uncross-linked microspheres (8.27%) confirming better drug retention efficiency (p < 0.01).