Glycerol monooleate/solvents systems for progesterone transdermal delivery: In vitro permeation and microscopic studies

Abstract

Transdermal delivery of most drugs is precluded by the barrier characteristics of the stratum corneum (SC). Chemical penetration enhancers are capable of interacting with SC constituents, inducing a temporary reversible increase in the skin permeability. The aim of this work was to assess the influence of glycerol monooleate (GMO)/solvents systems on percutaneous absorption across hairless mouse SC of a lipophilic drug, progesterone (PG), as well as its effect on the SC structural characteristics, by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The morphological changes observed in the hairless mouse SC suggest a GMO effect on the skin barrier. In addition, the increase in the in vitro PG flux and in vivo penetration of a fluorescent label point towards GMO as a potential absorption enhancer. The results obtained showed that GMO/solvents systems provoked changes in the SC that could be causing increased permeation of PG across hairless mouse skin, optimising in this way the transdermal delivery of this drug.

QbD based approach for optimization of Tenofovir disoproxil fumarate loaded liquid crystal precursor with improved permeability

“…It is put onto the records that GMO having polar head and nonpolar carbon chain with a low melting point increases permeability of membrane by disordering intercellular lipid. Further, the interaction between polar head of phospholipid and a hydroxyl group of GMO has been identified as a possible mechanism for permeation enhancement of drugs by transdermal route [37] , [38] . It is believed that similar mechanisms might have been responsible for enhancing permeation flux and coefficient values of TDF by oral route along with bioadhesive nature of GMO increasing residence time in GI tract.…”

Evaluation of skin absorption of drugs from topical and transdermal formulations

“…The main advantage of CLSM is that it enables characterization of the skin in depth at different focal planes. Thus, the images generated at different planes are combined to obtain a 3D image of the sample (Caspers et al, 1998;Pereira et al, 2002;Das, Agrawal, 2011;Mateus et al, 2013).…”

Influence of monoolein on progesterone transdermal delivery

“…Pereira et al (2002) studied transdermal delivery of PG from MO dispersed in mineral oil (at 20%) and observed a 3-fold enhance in PG delivery over control (240 and 80 µg/cm 2 , respectively, after 48 h of experiment). However, authors used mice skin as a model, whose SC is much thinner than porcine and human skin, compromising the comparison with the data presented in this paper.…”

“…Absorption enhancers reversibly decrease skin barrier resistance, allowing the drug to penetrating viable tissues to act locally and/or reach the systemic circulation (Alexander et al, 2012). Monoolein (MO, Figure 2) is one of the most studied absorption enhancer (Simonetti et al, 2009;Herai et al, 2007;Steluti et al, 2001;Lopes, Collett, Bentley, 2005;Pereira et al, 2002;Puglia et al, 2013). It is pharmacologically inert, non-toxic, immediate and reversible in action, non-irritating, non-allergenic, odorless, colorless and chemically and physically compatible with many drugs and pharmaceutical excipients (Hadgraft, 1999;Qiu, Caffrey, 2000).…”

“…It is pharmacologically inert, non-toxic, immediate and reversible in action, non-irritating, non-allergenic, odorless, colorless and chemically and physically compatible with many drugs and pharmaceutical excipients (Hadgraft, 1999;Qiu, Caffrey, 2000). MO is able to interact with phospholipid bilayers of SC lipid matrix and destabilize its structure momentarily (Pereira et al, 2002). However, due to its high lipophilicity, MO is rarely incorporated in formulations containing lipophilic active agents, such as PG, since high interaction with the absorption enhancer could hinder drug release, hindering drug transdermal permeation.…”