Modulation of two stable W/O/W multiple emulsions to control delivery of a hydrophilic drug through the skin

V. MOURIÑO AND R. SERRAO

Manchester International Convention Centre (4-6 September)

Conferencia; British Pharmaceutical Conference; 2006

Royal Pharmaceutical Society of Great Britain

Different strategies have been used in order to improve the diffusion of molecules through the skin. Vehicles can affect both drug delivery and skin permeability properties (Bonina et al 1993). Multiple emulsions are of interest because of their ability to provide sustained release (Raynal et al 1993). By enhancing drug accumulation at the site of administration, multiple emulsions may improve its activity and reduce serious side effects due to undesirable systemic absorption (Youenang Piemi et al 1998). Two water-in-oil-in-water (w/o/w) multiple emulsions (CME1–01 and CME1–02) were obtained for dermato-cosmetic purpose. Caffeine (CAF) was used as a drug model placed in the inner hydrophilic phase of both multiple emulsions (ME). The aims of this study were: to show the ability of CME1–01 and CME1–02 to control the delivery of caffeine (CAF) at the target site, when they were compared with the release profile of CAF from an O/W emulsion of similar composition; and to show the possibility to adjust the release of drugs through the skin by only changing the composition of the Lipophilic emulsifier system (LES). Lipophilic and hydrophilic silicones copolyoles were used as emulsifiers to formulate two multiple emulsions at room temperature using caffeine in the inner phase as a hydrophilic drug model and a mix of reological additives in the external phase. A two-step process was used for the preparations of both ME (Raynal et al 1993). The only difference between both of them was the composition of LES, even though; the total percentage of the lipophilic emulsifier system remained stable. CME1–02 was made by using a mix of PEG/PPG-18/18 Dimethicone and Cethyl PEG/PPG-10/1 Dimethicone (1:5) while CME1–01 had only Cethyl PEG/PPG-10/1 Dimethicone. The delivery behaviour of CAF from both ME were investigated and compared through in vitro skin distributions and permeation studies using Franz cells (Youenang Piemi et al 1998). The cumulative amount of CAF permeated after 3 h (express per ml and cm2) of CEM1–01, CEM1–02 and CA1–00 were 0.52 ± 0.04; 0.15 ± 0.02; 1.02 ± 0.08, respectively. The cumulative amount of CAF permeated after 6 h (express per ml and cm2) of CEM1–01, CEM1–02 and CA1–00 were 1.10 ± 0.08; 0.50 ± 0.06; 2.62 ± 0.13, respectively. Both ME studied controlled the release of CAF when they were compared with an O/W emulsion (CA1–00) of similar composition (P < 0.05, n = 5). When both formulations (CEM1–01 and CEM2–02) were compared each other, they showed significant different release profiles (P < 0.05, n = 5). There is a possibility to adjust the release of drugs from a ME through the skin by changing the composition of the LES. Bonina et al (1993) Int. J. Pharm. 102: 19–24 Raynal et al (1993) J. Controlled Release 26: 129–140 Youenang Piemi et al (1998) Int. J. Pharm. 171: 207–215