Abstract
Objective: Exemestane is an anti-breast cancer drug, possesses low water solubility and low permeability. This work aimed at the cause-effect relations and optimization of exemestane-loaded nanostructured lipid carriers (EXE-NLCs) for oral delivery.Methods: Excipient screening was based on exemestane solubilities and the emulsification efficiency of surfactants. A D-optimal design based on three independent variables was applied to evaluate the cause-effect relations and optimise EXE-NLCs formulation. The particle size (PS), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL) were investigated with respect to three independent variables including liquid lipid to total lipid ratio (X1), surfactant concentration (X2), total lipid concentration (X3).Results: EXE-NLCs were prepared by a hot sonication method employing Labrafac CC and Compritol 888ATO as liquid and solid lipids, respectively, and Cremophor RH40 as a surfactant and Lutrol E-400 as a co-surfactant. All investigated factors: liquid lipid to total lipid ratio, surfactant concentration and total lipid concentration showed significant influences on physicochemical characteristics of EXE-NLCs. The optimal EXE-NLC formulation was composed of liquid lipid to total lipid ratio (X1) of 24 % (w/w), surfactant concentration (X2) of 4 % (w/v) and total lipid concentration (X3) of 4 % (w/v). The PS, PDI, EE and DL of the optimized EXE-NLCs were found to be 41.787 nm; 0.11; 97.605 % and 1.935 %, respectively. The optimized formulation was experimentally examined which demonstrated a good agreement between experimental and predicted values.Conclusion: The cause-effect relations and optimization of EXE-NLCs were investigated and reported for the first time. EXE-NLCs formulation was successfully optimized using D-optimal design and merits further study.
Highlights
Exemestane is an anti-breast cancer drug inhibits irreversibly the activity of aromatase, the key enzyme that converts androgens to oestrogens [1]
A well-resolved HPLC chromatogram of exemestane was obtained following the use of an acetonitrile: water mobile phase in a ratio of (75:25, v/v)
The coefficient of variation of the within-day precision, expressed as relative standard deviation, was found to be 1.88 %. These results indicated that the method was reliable and reproducible
Summary
Exemestane (fig. 1) is an anti-breast cancer drug inhibits irreversibly the activity of aromatase, the key enzyme that converts androgens to oestrogens [1]. Exemestane has been approved by the food and drug administration (FDA) for the treatment of breast cancer in postmenopausal women [2]. Exemestane is a BCS (bio pharmaceutics classification system) class IV drug with a poor water solubility (0.08 mg/ml) and low permeability. The bioavailability of exemestane was reported to be low in various animal models at a single dose of 25 mg [3]. Different formulation strategies have been employed to overcome the aforementioned biopharmaceutical challenges associated with exemestane such as pro-liposomes [4], polycaprolactone nanoparticles [5], poly (D, L-lactide-co-glycolide)/montmorillonite nanoparticles [6], polymeric nanoparticles [7] and self-emulsifying drug delivery system [3].
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