Development of Solid Self-Emulsifying Formulation for Improving the Oral Bioavailability of Erlotinib

Abstract

Abstract. To improve the solubility and oral bioavailability of erlotinib, a poorly water-soluble anticancer drug, solid self-emulsifying drug delivery system (SEDDS) was developed using solid inert carriers such as dextran 40 and Aerosil® 200 (colloidal silica). The preliminary solubility of erlotinib in various oils, surfactants, and co-surfactants was determined. Labrafil M2125CS, Labrasol, and Transcutol HP were chosen as the oil, surfactant, and co-surfactant, respectively, for preparation of the SEDDS formulations. The ternary phase diagram was evaluated to show the self-emulsifying area. The formulations were optimized using the droplet size and polydispersity index (PDI) of the resultant emulsions. Then, the optimized formulation containing 5% Labrafil M2125CS, 65% Labrasol, and 30% Transcutol was spray dried with dextran or Aerosil® and characterized for surface morphology, crystallinity, and pharmacokinetics in rats. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) exhibited the amorphous form or molecular dispersion of erlotinib in the formulations. The pharmacokinetic parameters of the optimized formulations showed that the maximum concentration (C max ) and area under the curve (AUC) of erlotinib were significantly increased, compared to erlotinib powder (p<0.05). Thus, this SEDDS could be a promising method for enhancing the oral bioavailability of erlotinib.

Systematic development of optimized SNEDDS of artemether with improved biopharmaceutical and antimalarial potential

“…Higher solubility of the drug in MCTs than in the LCTs can be attributed to the shorter chain length of the former lipids, which provide ease of solubilization of the drug, plausibly owing to higher surface area (Shah et al, 1994). Besides, the higher solubility of the drug in nonionic surfactants can be explained as a function of their lower HLB value, which favors faster solubilization of the lipophilic drugs and imparts spontaneous emulsification ability (Truong et al, 2015). The presence of cosolvent additionally helped in improving the solubility of drug by their solubilization capacity owing to the presence of longchain fatty alcohols (Mullertz et al, 2010).…”

“…Despite influence of the type of lipidic and emulsifying excipients for enhancing the oral bioavailability of drugs from the isotropic systems, identifying the rational combination of excipients helps in developing the impeccable formulations with robust performance Keohane et al, 2015;Truong et al, 2015;Beg et al, 2015b). The said objectives can be accomplished by systematic optimization using Design of Experiments (DoE) established to be markedly superior over the traditional one-factorat-a-time (OFAT) approach (Singh et al, 2005a).…”

Novel Approaches for Efficient Delivery of Tyrosine Kinase Inhibitors

“…Solidification of these delivery systems is the beneficial procedure to overcome this problem (77)(78). In a study was performed by Truong et al solid SEDDS formulations of Erlotinib were prepared by spray drying method (79). Erlotinib belongs to the (BCS) class II with low solubility and high permeability.…”

“…Their results demonstrated that Erlotinib was in the amorphous state in solid SEDDS and exhibited faster dissolution rate than pure drug. Their pharmacokinetic studies in rats indicated that bioavailability of Erlotinib in these formulations was improved in comparison to pure drug (79).…”

Untitled

“…Hence, formulations F8 were selected for further evaluation studies of zeta potential Table 4. Emulsification Time: It has been suggested that the mechanism of self-emulsification involves attrition of a fine cloud of small droplets from the surface of large droplets, instead of progressive reduction in droplet size 9 . Table 5 shows that, as the concentration of surfactant increases, the spontaneity of emulsification process increases.…”