Penetration enhancer-containing vesicles (PEVs) as carriers for cutaneous delivery of minoxidil

• Published in: International journal of pharmaceutics Vol. 380; no. 1; pp. 72 - 79
• Main Authors: Mura, Simona, Manconi, Maria, Sinico, Chiara, Valenti, Donatella, Fadda, Anna Maria
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.10.2009; Elsevier
• Subjects: Administration, Cutaneous; Animals; Animals, Newborn; Biological and medical sciences; Cineole; Cyclohexanols - chemistry; Deformable liposomes; Drug Carriers - chemical synthesis; Drug Compounding - methods; Drug Stability; Ethylene Glycols - chemistry; General pharmacology; Glycerides; Labrasol; Lecithins - chemistry; Liposomes - chemical synthesis; Medical sciences; Minoxidil; Minoxidil - administration & dosage; Monoterpenes - chemistry; Organic Chemicals - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Skin Absorption; Skin delivery; Solubility; Swine; Transcutol; Labrasol; Deformable liposomes; Minoxidil; Skin delivery; Transcutol; Cineole; Vesicle; Pharmaceutical technology; Vasodilator agent; Liposome; Expectorant; Percutaneous route; Eucalyptol; Piperidine derivatives; Microparticle; Antihypertensive agent; Absorption enhancer; Topical administration
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2009.06.040

The aim of this work was to evaluate the ability of a few different penetration enhancers to produce elastic vesicles with soy lecithin and the influence of the obtained vesicles on in vitro (trans)dermal delivery of minoxidil. To this purpose, so-called Penetration Enhancer-containing Vesicles (PEVs) were prepared as dehydrated–rehydrated vesicles by using soy lecithin and different amounts of three penetration enhancers, 2-(2-ethoxyethoxy)ethanol (Transcutol ®), capryl-caproyl macrogol 8-glyceride (Labrasol ®), and cineole. Soy lecithin liposomes, without penetration enhancers, were used as control. Prepared formulations were characterized in terms of size distribution, morphology, zeta potential, and vesicle deformability. The influence of PEVs on (trans)dermal delivery of minoxidil was studied by in vitro diffusion experiments through newborn pig skin in comparison with traditional liposomes and ethanolic solutions of the drug also containing each penetration enhancer. A skin pre-treatment study using empty PEVs and conventional liposomes was also carried out. Results showed that all the used penetration enhancers were able to give more deformable vesicles than conventional liposomes with a good drug entrapment efficiency and stability. In vitro skin penetration data showed that PEVs were able to give a statistically significant improvement of minoxidil deposition in the skin in comparison with classic liposomes and penetration enhancer-containing drug ethanolic solutions without any transdermal delivery. Moreover, the most deformable PEVs, prepared with Labrasol ® and cineole, were also able to deliver to the skin a higher total amount of minoxidil than the PE alcoholic solutions thus suggesting that minoxidil delivery to the skin was strictly correlated to vesicle deformability, and therefore to vesicle composition.