Optimization of self-emulsifying drug delivery system of cefuroxime axetil

Overcoming solubility problems is the greatest challenge during formulation of poorly soluble active pharmaceutical ingredients (API’s) into oral solid dosage forms. Different formulation approaches were used to surpass this problem and enhance their solubility in the gastrointestinal (GI) fluids, in order to achieve a faster dissolution and better absorption, which will directly influence their therapeutic effect. In this paper, an evaluation of the potential of a self-emulsifying drug delivery system (SEDDS) to improve the solubility of the active ingredient cefuroxime axetil (CA) was done. Screening of the solubility of the API in different excipients was done, and Tween 80, PEG 400, and Olive oil as a surfactant, co-solvent, and oil, respectively, were chosen as the most convenient system constituents. An optimal self-emulsification and solubilization ability of this system was assessed using mixture experimental design statistical tools based on the response surface methodology (RSM). The prepared CA-SEDDS were evaluated for droplet size (d10, d50, d90 in µm), droplet size distribution (Span factor), and absorbance. As a complementary approach, for better representation of the non-linear relationship between the formulation compositions and the observed dispersion characteristics an artificial neural network (ANN) was used. Optimal formulation that consists of 10% (w/w) Tween 80 as surfactant, 80% (w/w) PEG 400 as co-solvent and 10% (w/w) Olive oil, was obtained. Both, mixture experimental design and ANN were combined for a comprehensive evaluation of CA-SEDDS and the obtained results suggested that formulation of SEDDS is a useful approach for improving the solubility of the CA. Keywords: self-emulsifying drug delivery systems (SEDDS), cefuroxime axetil, design of experiment, artificial neural network (ANN)

Modeling the Effect of Composition on Formation of Aerosolized Nanoemulsion System Encapsulating Docetaxel and Curcumin Using D-Optimal Mixture Experimental Design

The synergistic anticancer effect of docetaxel (DTX) and curcumin (CCM) has emerged as an attractive therapeutic candidate for lung cancer treatment. However, the lack of optimal bioavailability because of high toxicity, low stability, and poor solubility has limited their clinical success. Given this, an aerosolized nanoemulsion system for pulmonary delivery is recommended to mitigate these drawbacks. In this study, DTX- and CCM-loaded nanoemulsions were optimized using the D-optimal mixture experimental design (MED). The effect of nanoemulsion compositions towards two response variables, namely, particle size and aerosol size, was studied. The optimized formulations for both DTX- and CCM-loaded nanoemulsions were determined, and their physicochemical and aerodynamic properties were evaluated as well. The MED models achieved the optimum formulation for DTX- and CCM-loaded nanoemulsions containing a 6.0 wt% mixture of palm kernel oil ester (PKOE) and safflower seed oils (1:1), 2.5 wt% of lecithin, 2.0 wt% mixture of Tween 85 and Span 85 (9:1), and 2.5 wt% of glycerol in the aqueous phase. The actual values of the optimized formulations were in line with the predicted values obtained from the MED, and they exhibited desirable attributes of physicochemical and aerodynamic properties for inhalation therapy. Thus, the optimized formulations have potential use as a drug delivery system for a pulmonary application.

Omega-3 Self-Nanoemulsion Role in Gastroprotection against Indomethacin-Induced Gastric Injury in Rats

Peptic ulcer disease is an injury of the alimentary tract that leads to a mucosal defect reaching the submucosa. This study aimed to formulate and optimize omega-3 oil as a self-nanoemulsifying drug delivery system (SNEDDS) to achieve oil dispersion in the nano-range in the stomach to augment omega-3 oil gastric ulcer protection efficacy. Three SNEDDS components were selected as the design factors: the concentrations of the oil omega-3 (X1, 10–30%), the surfactant tween 20 and Kolliphor mixture (X2, 20–40%), and the cosurfactant transcutol (X3, 40–60%). The mixture experimental design proposed twenty-three formulations with varying omega-3 SNEDDS formulation component percentages. The optimized omega-3 SNEDDS formula was investigated for gastric ulcer protective effects by evaluating the ulcer index and by the determination of gastric mucosa oxidative stress parameters. Results revealed that optimized omega-3-SNEDDS achieved significant improvement in the gastric ulcer index in comparison with pure omega-3 oil. Histopathological findings confirmed the protective effect of the formulated optimized omega-3 SNEDDS in comparison with omega-3 oil. These findings suggest that formulation of omega-3 in the form of a SNEDDS would be more effective in gastric ulcer protection than the administration of omega-3 as a crude oil.