LECITHINISED MICROEMULSIONS FOR TOPICAL DELIVERY OFTRETINOIN

Tretinoin is indicated for the management of acne, photoaged skin, psoriasis and other skin disorders and also for severe conditions like acute promyelocytic anaemia and squamous cell carcinoma of the skin. The potential of tretinoin in these conditions is limited due to want of a proper delivery vehicle. In order to develop alternate formulations for the topical administration of tretinoin, lecithinsed microemulsions were prepared and evaluated as delivery vehicles. These systems were prepared using phosphate buffer pH 5.5, isopropyl myristate, tween 80 and ethanol. The microemulsions were characterized using TEM. The ability of the system to deliver tretinoin into and through the skin was evaluated in vitro using the skin of laca mice. The in vitro permeation data showed that the novel microemulsions increased tretinoin penetration through the skin; higher flux (33.92 µg / cm2 / hr) was obtained with microemulsion formulation and microemulsified gel (31.54 µg / cm2 / hr) in comparison to the plain drug solution (22.33 µg / cm2 / hr), plain drug in gel (28.67 µg / cm2 / hr) and the marketed preparation (24.28 µg / cm2 / hr). These results were supported by skin retention study and it was noted that the maximum amount retained was with microemulsified gel (96.28 µg / cm2) and non-gel (82.13 µg / cm2) respectively. The other systems; drug in solution, drug in gel (conventional) and marketed preparation were able to retain the drug at the level of 32.4 µg/ cm2, 21.54 µg / cm2 and 29.32 µg / cm2 respectively. These results suggest that the studied microemulsions may be appropriate vehicles for topical delivery of tretinoin.

[1]  H. Gollnick,et al.  The Retinoids , 1987, Drugs.

[2]  M. Kreilgaard Dermal Pharmacokinetics of Microemulsion Formulations Determined by In Vivo Microdialysis , 2001, Pharmaceutical Research.

[3]  P. Constantinides,et al.  Lipid Microemulsions for Improving Drug Dissolution and Oral Absorption: Physical and Biopharmaceutical Aspects , 1995, Pharmaceutical Research.

[4]  M. Lawrence,et al.  Formulation of electrically conducting microemulsion-based organogels. , 2003, International journal of pharmaceutics.

[5]  Mads Kreilgaard,et al.  Influence of microemulsions on cutaneous drug delivery. , 2002, Advanced drug delivery reviews.

[6]  Paloma Frutos,et al.  Amphotericin B in oil-water lecithin-based microemulsions: formulation and toxicity evaluation. , 2002, Journal of pharmaceutical sciences.

[7]  M Brisaert,et al.  Liposomes with tretinoin: a physical and chemical evaluation. , 2001, Journal of pharmaceutical and biomedical analysis.

[8]  J. Jaroszewski,et al.  NMR characterisation and transdermal drug delivery potential of microemulsion systems. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[9]  M. Delgado-Charro,et al.  Microemulsions for topical delivery of 8-methoxsalen. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[10]  S. Tenjarla Microemulsions: an overview and pharmaceutical applications. , 1999, Critical reviews in therapeutic drug carrier systems.

[11]  M. Poelman,et al.  Bicontinuous sucrose ester microemulsion: a new vehicle for topical delivery of niflumic acid , 1998 .

[12]  G. Koper,et al.  BRANCHING AND PERCOLATION IN LECITHIN WORMLIKE MICELLES STUDIED BY DIELECTRIC SPECTROSCOPY , 1998 .

[13]  P. Constantinides,et al.  Formulation and physical characterization of water-in-oil microemulsions containing long- versus medium-chain glycerides , 1997 .

[14]  M. Bentley,et al.  The influence of lecithin and urea on the in vitro-permeation of hydrocortisone acetate through skin from hairless mouse , 1997 .

[15]  M. Gasco,et al.  MICROEMULSIONS IN THE PHARMACEUTICAL FIELD : PERSPECTIVES AND APPLICATIONS , 1997 .

[16]  José Blanco-Méndez,et al.  Delivery of a hydrophilic solute through the skin from novel microemulsion systems , 1997 .

[17]  K. Goa,et al.  Tretinoin. A review of its pharmacodynamic and pharmacokinetic properties and use in the management of acute promyelocytic leukaemia. , 1995, Drugs.

[18]  P. Constantinides,et al.  Particle size determination of phase-inverted water-in-oil microemulsions under different dilution and storage conditions , 1995 .

[19]  M. Gallarate,et al.  Preparation and evaluation in vitro of solutions and o/w microemulsions containing levobunolol as ion-pair. , 1993 .

[20]  S. Benita,et al.  Submicron emulsions as colloidal drug carriers for intravenous administration: comprehensive physicochemical characterization. , 1993, Journal of pharmaceutical sciences.

[21]  S. Benita,et al.  Drug release from submicronized o/w emulsion: a new in vitro kinetic evaluation model , 1990 .

[22]  R. Evans,et al.  Nuclear receptor that identifies a novel retinoic acid response pathway , 1990, Nature.

[23]  N. Smith,et al.  Hyperkeratotic porokeratosis (Mibelli) with psoriasis—response to an aromatic retinoid , 1984, Clinical and experimental dermatology.