This study was conducted to develop an emulgel formulation of chlorphenesin (CHL) using 2 types of gelling agents: hydroxypropylmethyl cellulose (HPMC) and Carbopol 934. The influence of the type of the gelling agent and the concentration of both the oil phase and emulsifying agent on the drug release from the prepared emulgels was investigated using a 2 3 factorial design. The prepared emulgels were evaluated for their physical appearance, rheological behavior, drug release, antifungal activity, and stability. Commercially available CHL topical powder was used for comparison. All the prepared emulgels showed acceptable physical properties concerning color, homogeneity, consistency, spreadability, and pH value. They also exhibited higher drug release and antifungal activity than the CHL powder. It was found that the emulsifying agent concentration had the most pronounced effect on the drug release from the emulgels followed by the oil phase concentration and finally the type of the gelling agent. The drug release from all the emulgels was found to follow diffusion-controlled mechanism. Rheological studies revealed that the CHL emulgels exhibited a shear-thinning behavior with thixotropy. Stability studies showed that the physical appearance, rheological properties, drug release, and antifungal activity in all the prepared emulgels remained unchanged upon storage for 3 months. As a general conclusion, it was suggested that the CHL emulgel formulation prepared with HPMC with the oil phase concentration in its low level and emulsifying agent concentration in its high level was the formula of choice since it showed the highest drug release and antifungal activity.
Aim
Agomelatine (AGM) is the first melatonergic antidepressant. It suffers from low oral bioavailability (<5%) due to extensive hepatic metabolism. The current work aimed to develop an alternative AGM-loaded invasomes to enhance transdermal drug bioavailability.
Methodology
AGM-loaded invasomes were developed using two drug: lipid ratios (1:10 or 1:7.5), four terpene types (limonene, cineole, fenchone or citral) and two terpene concentrations (0.75% or 1.5%, w/v). They were characterized for drug entrapment efficiency (EE%), particle size (PS), zeta potential (ZP) and drug released percentages after 0.5h (Q
0.5h
) and 8h (Q
8h
). The optimum invasomes (I1, I2 and I4) were evaluated for morphology, drug-crystallinity, and ex-vivo drug flux. The variables influencing sonophoresis of the best achieved invasomal gel system (I2) were optimized including, ultrasound frequency (low, LFU or high, HFU), mode (pulsed or continuous), application period (10 min or 15 min) and duty cycle (50% or 100%). AGM pharmacokinetics were evaluated in rabbits following transdermal application of I2-LFU-C4 system, relative to AGM oral dispersion.
Results
The superiority of I2 invasomes [comprising AGM and phosphatidylcholine (1:10) and limonene (1.5% w/v)] was statistically revealed with respect to EE% (78.6%), PS (313 nm), ZP (−64 mV), Q
0.5h
(30.1%), Q
8h
(92%), flux (10.79 µg/cm2/h) and enhancement ratio (4.83). The optimum sonophoresis conditions involved application of LFU in the continuous mode for 15 min at a 100% duty cycle (I2-LFU-C4 system). The latter system showed significantly higher C
max
, and relative bioavailability (≈ 7.25 folds) and a similar T
max
(0.5 h).
Conclusion
I2-LFU-C4 is a promising transdermal system for AGM.
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