Preparation and Evaluation of Solid-Self-Emulsifying Drug Delivery System Containing Paclitaxel for Lymphatic Delivery

Abstract

Solid-self-emulsifying drug delivery system (S-SEDDS) of paclitaxel (Ptx) was developed by the spray drying method with the purpose of improving the low bioavailability (BA) of Ptx. 10% oil (ethyl oleate), 80% surfactant mixture (Tween 80 : Carbitol, 90 : 10, w/w), and 10% cosolvent (PEG 400) were chosen according to their solubilizing capacity. The mean droplet size, zeta potential, and encapsulation efficiency of the prepared S-SEDDS were 16.9 ± 1.53 nm, 12.5 ± 1.66 mV, and 56.2 ± 8.1%, respectively. In the S-SEDDS, Ptx presents in the form of molecular dispersion in the emulsions or is distributed in an amorphous state or crystalline with very small size. The prepared S-SEDDS formulation showed 70 and 75% dissolution in 60 and 30 min in dissolution medium pH 1.2 and 6.8, respectively. Significant increase (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>P</mml:mi><mml:mo>≤</mml:mo><mml:mn fontstyle="italic">0.05</mml:mn></mml:math>) in the peak concentration (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mrow><mml:msub><mml:mrow><mml:mi>C</mml:mi></mml:mrow><mml:mrow><mml:mi mathvariant="normal">m</mml:mi><mml:mi mathvariant="normal">a</mml:mi><mml:mi mathvariant="normal">x</mml:mi></mml:mrow></mml:msub></mml:mrow></mml:math>), the area under the curve (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi mathvariant="normal">A</mml:mi><mml:mi mathvariant="normal">U</mml:mi><mml:msub><mml:mrow><mml:mi mathvariant="normal">C</mml:mi></mml:mrow><mml:mrow><mml:mn mathvariant="normal">0</mml:mn><mml:mtext>–</mml:mtext><mml:mi mathvariant="normal">∞</mml:mi></mml:mrow></mml:msub></mml:math>), and the lymphatic targeting efficiency of Ptx was observed after the oral administration of the Ptx-loaded S-SEDDS to rats (20 mg/kg as Ptx). Our research suggests the prepared Ptx-loaded S-SEDDS can be a good candidate for the enhancement of BA and targeting drug delivery to the lymphatic system of Ptx.