Modulation of stable W/O/W multiple emulsions to target the epidermis and decrease the percutaneous absorption of a hydrophilic drug

V. MOURIÑO AND R. SERRAO

Manchester International Convention Centre (8-10 September)

Conferencia; British Pharmaceutical Conference; 2007

Royal Pharmaceutical Society of Great Britain

Objectives The aim of this study was to evaluate the influences of two different W/O/W multiple emulsions (CME1-01 and CME1-02) on the penetration of caffeine through the skin when they were compared with an O/W emulsion (CA1-00) of similar composition. 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). Methods Lipophilic and hydrophilic silicones copolyoles were used as emulsifiers to formulate two stable W/O/W multiple emulsions (ME) at room temperature using 1% caffeine (CAF) in the inner phase as a hydrophilic drug model and a mix of reological additives in the external phase (Mouriño de Cortese et al 2006). A two-step process was used for the preparations of both ME (Raynal et al 1993). The total percentage of the liphophilic emulsifier system (LES) remained stable; the only difference between both of them was the composition of LES. CME1-02 was made by using a mix of PEG/PPG-18/18 dimeticone and Cethyl PEG/PPG-10/1 dimeticone (1:5), while CME1-01 had only Cethyl PEG/PPG-10/1 dimeticone. To avoid any influence of the ingredients of the formulations and to study only the effect of the emulsion type, the multiple emulsions and the O/W emulsion (CA1-00) were prepared with exactly the same composition. The distribution of CAF within skin tissue was studied by the tape stripping method after 24-h in vitro permeation study using Franz Cells. Caffeine levels were analysed in epidermis and dermis, by liquid chromatography. Results The topic application of both formulations studied (CME1-01 and CME1-02) significantly reduced the amount of CAF permeated when compared with the O/W emulsion (CA1-01) as discussed in previous works (Mouriño de Cortese et al 2006). In addition, the amount of CAF trapped in the epidermis after a 24-h in vitro permeation study was significantly higher when CME1-01 and CME1-02 were compared with CA1-01 (P < 0.05, n = 5). The total amount of CAF found in the epidermis after 24 h (expressed as a percentage of the applied dose) of CEM1-01, CEM1-02 and CA1-00 were 8.87 } 1.15; 8.52 } 2.53; 3.63 } 1.90, respectively. When both ME formulations (CEM1-01 and CEM2-02) were compared with each other, they did not show significant different release profiles (P < 0.05, n = 5). Conclusions Both formulations (CME1-01 and CME1-02) seemed to be efficient vehicles to control caffeine distribution within the skin despite the liphophilic emulsifier system used. Mouriño de Cortese, V., Serrao, R. (2006) J. Pharm. Pharmacol. Suppl. 1: A66 Raynal, et al (1993) J. Controlled Release 26: 129–140 Youenang Piemi, et al (1998) Int. J. Pharm. 171: 207–215