Evaluating the efficacy of different curcumin polymorphs in transdermal drug delivery

Abstract

Curcumin exists in three polymorphic forms: one monoclinic form and two orthorhombic forms. This work aims to investigate the efficacy of curcumin polymorphs in transdermal drug delivery by formulating curcumin polymorphs and their incorporation in polymeric films. Monoclinic form, Form 1, was precipitated by liquid antisolvent technique from acetone solutions, whereas orthorhombic form, Form 2, was obtained by vacuum evaporation of solutions of curcumin in a mixed solvent of chloroform and hexane (60:40%v/v). The other orthorhombic form, Form 3, was precipitated from dimethylsulfoxide solutions. All three curcumin polymorphs were incorporated into polymeric films made of low molecular weight hydroxypropyl methyl cellulose (HPMC E5LV) along with different plasticizers, and permeation enhancers. Radical scavenging activity and cytotoxicity of curcumin polymorphs on human melanoma cell lines were evaluated. Water uptake, in-vitro release, and in-vitro permeation studies on HPMC films loaded with curcumin polymorph were carried out. Cytotoxicity studies on human melanoma cells (SK-MEL-28) showed that Form 2 results in the highest cell inhibition. Among all three curcumin polymorphs, the free radical scavenging activity of Form 3 was found to be the highest. HPMC films loaded with Form 3 exhibited higher water uptake and higher curcumin release profiles at pH of 5.5 (95.3% in 20 h) and pH 7.4 (79.8% in 20 h) as well as the highest in-vitro permeation compared to the other two curcumin forms. Overall, orthorhombic curcumin polymorphs (i.e., Form 2 and Form 3) showed a higher propensity for transdermal drug delivery as compared to the monoclinic curcumin (Form 1).