Development of Transdermal Oleogel Containing Olmesartan Medoxomil: Statistical Optimization and Pharmacological Evaluation

Olmesartan medoxomil (OLM) is a first-line antihypertensive drug with low oral bioavailability (28.6%). This study aimed to develop oleogel formulations to decrease OLM side effects and boost its therapeutic efficacy and bioavailability. OLM oleogel formulations were composed of Tween 20, Aerosil 200, and lavender oil. A central composite response surface design chose the optimized formulation, containing Oil/Surfactant (SAA) ratio of 1:1 and Aerosil % of 10.55%, after showing the lowest firmness and compressibility, and the highest viscosity, adhesiveness, and bioadhesive properties (Fmax and Wad). The optimized oleogel increased OLM release by 4.21 and 4.97 folds than the drug suspension and gel, respectively. The optimized oleogel formulation increased OLM permeation by 5.62 and 7.23 folds than the drug suspension and gel, respectively. The pharmacodynamic study revealed the superiority of the optimized formulation in maintaining normal blood pressure and heart rate for 24 h. The biochemical analysis revealed that the optimized oleogel achieved the best serum electrolyte balance profile, preventing OLM-induced tachycardia. The pharmacokinetic study showed that the optimized oleogel increased OLM’s bioavailability by more than 4.5- and 2.5-folds compared to the standard gel and the oral market tablet, respectively. These results confirmed the success of oleogel formulations in the transdermal delivery of OLM.

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Materials

Olmesartan medoxomil was supplied by MultiApex Pharmaceutical Co. (Cairo, Egypt). Olmesartan (the active metabolite) was purchased from Santa Cruz Biotechnology Inc. (Santa Cruz, CA, USA). Lavender oil was from Pharmachem Pvt Ltd., Co. (Maharashtra, Mumbai, India). Tween 20, Aerosil 200, carboxy methylcellulose (CMC), Dexamethasone, and Fructose were from Sigma–Aldrich Co. (St. Louis, MO, USA). HPLC grade dexamethasone, triethylamine, ammonium acetate, acetonitrile, and methanol were purchased from Merck-Schuchardt Co. (Hohenbrunn, Bavaria, Germany). Angiosartan^® 10 mg oral tablet was from Chemiphar Co. (Cairo, Egypt).

Solubility Study

The solubility of OLM in different surfactants (Tween 20, Tween 80, Koliphor EL, and Koliphor RH 40) and different oils (lavender oil, olive oil, eucalyptus oil, and coconut oil) was assessed by utilizing the shake-flask technique [8]. In brief, excess amounts of OLM (50 mg) were added to different vials that contained 1 mL of the investigated surfactants or oils. Vials were set in a horizontal water bath shaker (PLT-110, Hyderabad, India) at 25 ± 0.5 °C for 24 h. The resulting mixtures were centrifuged at 3500 rpm for 15 min. The withdrawn supernatants were filtered using a membrane filter (0.45 µm), diluted with methanol, and then analyzed utilizing a spectrophotometer (Shimadzu, Kyoto, Japan) at λ_max 257 nm [5].

El-Dahmy, R.M.; Elsayed, I.; Hussein, J.; Althubiti, M.; Almaimani, R.A.; El-Readi, M.Z.; Elbaset, M.A.; Ibrahim, B.M.M. Development of Transdermal Oleogel Containing Olmesartan Medoxomil: Statistical Optimization and Pharmacological Evaluation. Pharmaceutics 2023, 15, 1083.
https://doi.org/10.3390/pharmaceutics15041083