Effect of Different Carriers on in vitro Permeation of Meloxicam through Rat Skin

Abstract

The ability of β-cyclodextrin, hydroxypropyl-β-cyclodextrin, polyvinyl pyrrolidone and urea to influence the percutaneous absorption of meloxicam through isolated rat skin was evaluated. Carrier complex were prepared by kneading method in 1:1 and 1:2 in molar ratios for β-cyclodextrin and hydroxypropyl-β-cyclodextrin and in 1:1, 1:3 and 1:5 in weight ratios for polyvinyl pyrrolidone and urea. The complexes were characterized by IR, DSC and evaluated for solubility, dissolution and skin permeability. The solubility, dissolution and permeability of meloxicam were enhanced by using the carriers. The influence of cyclodextrins, polyvinyl pyrrolidone and urea on in vitro permeation of meloxicam through rat skin was investigated by incorporation of prepared carrier complex in 1% carbopol gel. The prepared gel was evaluated for drug content, pH and viscosity and in vitro permeation. All the percutaneous parameters like flux (Jss), amount permeated (Q(6)), diffusivity (D), permeability coefficient (K(p)), partition coefficient (K) and release rate constant (k) were calculated statistically. In vitro permeation study showed the trend that the penetration flux and enhancement factor increases with increasing concentration of β-cyclodextrin and hydroxypropyl-β-cyclodextrin and then decrease dramatically in case of hydroxypropyl-β-cyclodextrin gel formulation with the increase to 1:2 ratio. Similar changes in pattern of permeation were also observed with polyvinyl pyrrolidone and urea carrier complex. These findings concluded that the carriers cyclodextrins, polyvinyl pyrrolidone and urea could be used as transdermal permeation enhancer in topical preparation of meloxicam.

Keywords: hydroxypropyl-β-cyclodextrin; in vitro release; meloxicam; permeation; polyvinyl pyrrolidone; urea; β-cyclodextrin.

Fig. 1

IR Spectra of pure meloxicam and meloxicam-carrier complexes IR Spectra of (a) pure meloxicam (M); (b) meloxicam-β-cyclodextrin complex (B2); (c) meloxicam-hydroxypropyl-β-cyclodextrin complex (H2); (d) meloxicam-polyvinyl pyrrolidone complex (P3); (e) meloxicam-urea complex (U3)

Fig. 2

DSC thermogram of pure meloxicam and selected meloxicam-carrier complexes DSC thermogram of (a) pure meloxicam (M); (b) meloxicam-β-cyclodextrin complex (B2); (c) meloxicam-hydroxypropyl-β-cyclodextrin complex (H2); (d) meloxicam-polyvinyl pyrrolidone complex (P3); (e) meloxicam-urea complex (U3).

Fig. 3

Dissolution profile of pure meloxicam and meloxicam-carrier complexes Dissolution profile of pure meloxicam M(–◆–); meloxicam: β-cyclodextrin complex in 1:1 (–■–) and 1:2 (–▲–); meloxicam: hydroxypropyl-β-cyclodextrin complex 1:1 (–×–) and 1:2 (–×–); meloxicam: polyvinyl pyrrolidone complex 1:1 P1G (–○–), 1:3 P3G (–|–), 1:5 P5G (–Δ–); meloxicam and urea 1:1 U1G (–□–), 1:3 U3G (–□–) and 1:5 (–Δ–) ratios shows increase in dissolution rate as the concentration of carriers was increased

Fig. 4

Comparative permeation study of pure meloxicam with meloxicam- carrier complexes through rat skin after 6 h pure meloxicam M, drug-carrier complexes B1, B2, H1, H2, P1, P3, P5, U1, U3,U5 in different ratios

Fig. 5

Comparative in vitro release profile of meloxicam from different gel In vitro release of meloxicam from gel with pure meloxicam MG (–◆–), gel containing meloxicam: β-cyclodextrin complex in 1:1 B1G (–■–) and 1:2 B2G (–▲–); meloxicam: hydroxypropyl-β- cyclodextrin complex in 1:1 H1G (–×–)and 1:2 H2G (–×–); meloxicam: pvp complex in 1:1 P1G (–■–), 1:3 P3G (–|–) and 1:5 P5G (–○–); meloxicam: urea complex in 1:1 U1G (–––), 1:3 U3G (–□–) and 1:5 U5G (–Δ–)

Fig. 6

Comparative permeation profile of meloxicam from different gelsPlain gel MG (–◆–), gel containing meloxicam: b-cyclodextrin complex in 1:1 B1G(–■–) and 1:2 B2G (–▲–); meloxicam: hydroxypropyl-bcyclodextrin complex in 1:1 H1G (–■–) and 1:2 H2G (–◊–);meloxicam: polyvinyl pyrrolidone complex in 1:1 P1G (–■–), 1:3P3G (–|–) and 1:5 P5G (–□–); meloxicam: urea complex in 1:1 U1G (–○–), 1:3 U3G (–––) and 1:5 U5G (–●–)

Fig. 7

Comparative amount of meloxicam retained in skin after 6 h from different gels Gel with pure meloxicam (MG), gels with drug-βCD complex (B1G, B2G), gels with drug-HPβCD complex (H1G, H2G), gels with drug-PVP complex (P1G, P3G and P5G), gels with drug-urea complex (U1G, U3G, and U5G)