Preparation and Characterization of Etodolac Bearing Emulsomes

Abstract

Objective: Emulsomes are novel vesicular drug delivery system with an internal solid lipid core surrounded by one or more bilayers of phospholipids. Etodolac is a potent anti-inflammatory drug and is a drug of choice for the treatment of various diseases. The present study is focused on the development of emulsomes using etodolac as drug candidates having improved drug loading with sustained-release effect for patient compliance.
 Methods: Emulsomes formulation composed of solid lipids (tristearin), phospholipids, cholesterol, stearylamine, and drug (etodolac) were prepared by lipid film hydration method followed by sonication to produce emulsomes of the nanometric size range. All the formulations were optimized by using box-behnken design of experiment considering 3 factors viz. drug to phospholipid ratio (A), tristearin to phospholipid ratio (B), stearylamine to phospholipid ratio (C) at 3 levels lower (-1), middle (0) and upper (+1). The response of the independent variables (A, B, C) was studied on the dependent variable viz. particle size (Y1), zeta potential (Y2), and entrapment efficiency (Y3). The responses were analyzed by design expert software to find out the optimized values of variables within the design space.
 Results: Compatibility with excipients was established by FTIR studies. The developed emulsomes were spherical shape vesicles as analyzed by TEM. The optimized batch (OB) was evaluated for particle size, zeta potential, and entrapment efficiency with experimental values 383.1 ± 11.7 nm, 47.2 ± 1.3 mV and 80.1 ± 3.2% and predicted values 390.394 nm, 45.000 mV and 81.642 %, respectively. The experimental values were found in reasonable agreement with predicted values by the design of the experiment. In vitro drug release study showed sustained release of the drug (88.69 % after 24 h).
 Conclusion: Etodolac loaded emulsomes is a novel drug delivery system and found to reliable in terms of various characteristic parameters like particle size, zeta potential, entrapment efficiency, and drug release. 3-factors 3-levels Box-behnken design of the experiment is a suitable design for the optimization of emulsomes.

Nanostructured Lipid Carriers Engineered as Topical Delivery of Etodolac: Optimization and Cytotoxicity Studies

“…The “n” values (Korsmeyer-Peppas) indicated the combination of two release mechanism: drug diffusion and degradation of lipid matrix. The prolonged drug release from NLC formulations and similar results in ETD release were obtained in other studies [ 10 , 11 , 30 , 31 , 42 , 43 , 44 , 45 ].…”

“…For this purpose, the miscibility of lipid mixtures is assessed (mixture observation for the absence of phase separation) [12,34]. To elaborate the composition of NLC many statistical methods are used [27,31,35,36]. The study used fractional factorial design to plan the experiments and to define selected parameters that determine the obtained NLC.…”

“…ETD is available in oral forms (tablets, capsules) [ 29 , 30 ]. Oral therapy with ETD requires doses of 200–400 mg, every 6–8 h. Limiting the frequency of drug use, its dose, and the possible side effects (gastrointestinal disorders such as peptic ulcer or bleeding) is important issue in ETD therapy [ 30 , 31 , 32 ]. In order to reduce the side effects associated with the oral route, new ways of drug administration and modern carriers for lipophilic drugs are developed.…”

“…The value of the obtained EE% depends on many factors: the lipophilic properties of drug (lipophilic drugs show high EE% due to their high affinity for the lipid phase), the composition of the lipid phase (it affects for imperfection in lipid matrix), the addition of a surfactant but also the method of preparation [ 16 ]. The properties of liquid lipids in NLC increase the imperfections in the crystal structure in lipid matrix which contributes to the EE% increase [ 12 , 28 , 31 ]. In the study, the optimized NLC formulation (F9) was characterized by 275 nm of particles size, 0.55 of PDI, -33 mV of zeta potential and 86% of EE%.…”

“…The commonly used method in the assessment of drug release from NLC is the dialysis technique (with using the dialysis bags) [ 28 , 30 , 31 ]. The release of the drug from NLC depends on many factors, including: drug solubility, type of lipids and surfactants, the drug location in the NLC structure, and the method of preparation.…”