Preformulation studies with melanotan‐II: A potential skin cancer chemopreventive peptide

Melanotan‐II (1) is a cyclic heptapeptide analogue of α‐melanocyte‐stimulating hormone (α‐MSH) which tans the skin and is currently being evaluated for the prevention of sunlight‐induced skin cancers. The dissociation constants of 1 were determined using potentiometric titration and ultraviolet spectrophotometry. The _pK a 1, (histidine) and _pK a 2 (arginine) were estimated to be 6.54 and 11.72, respectively. The apparent partition coefficient (PC) was measured at three pH values using both n‐octanol and isooctane as the nonpolar phase. The PC(octanol) and Δlog PC at pH 7.35 were 2.82 and 1.05, respectively. These data, together with the observance of a bioavailability of 4.6% in the rat, indicate that 1 may be a suitable candidate for oral delivery. The data presented here are useful in developing an appropriate dosage form for 1.