A Preclinical Study of Novel Phentolamine Formulation and in Vitro/in Vivo Evaluation

Phentolamine (PT) is a non-selective a-adrenoceptor blocking agent. Oral and intracavernosal PT therapy are effective treatment options for erectile dysfunction. In the present study, a local therapy system of PT preparation was developed, by which its penetration enhancers, safety, stability and in vivo were investigated. The effect of permeation enhancers on in vitro mucosa permeability was assessed using sodium dodecyl sulphate (SDS), azone, propylene glycol (PG), Pharmasolve, Labrasol, Transcutol P, oleic acid, peppermint oil (lipophilicity), peppermint oil (hydrophilic) and their concentrations for absorption enhancement were optimized. The rabbit model was used to evaluate the safety and efficacy. peppermint oil appeared to be the most effective one for enhancing the mucosa permeation of PT than the other enhancers. These enhancements by peppermint oil were statistically significant (p<0.05) compared to control. The order of permeation enhancement was PO (hydrophilic)>PO (lipophilicity)>azone>Transcutol P≈Labrasol>SDS≈PG≈Pharmasolve≈oleic acid. Histological investigations were performed on buccal mucosa and indicated no major morphological changes. The enhancing effect of peppermint oil on the mucosa absorption of PT was evaluated from the mucoadhesive gels in rabbits. Phentolamine local therapy would produce an ideal therapeutic effect on ED.