Tablets Based on Compressed Zein Microspheres for Sustained Oral Administration: Design, Pharmacokinetics, and Clinical Study

Abstract

In our previous study, we reported a novel tablet based on compressed zein microspheres as a universal drug delivery system using the hydrophobic protein zein, which shows zero-order release in the presence of pepsin. However, this formulation had difficulty with disintegration under physiological conditions within 48 h, and thus could not be used directly for oral administration. In the present study, a formulation of ivermectin (IVM) tablets based on compressed zein microspheres was improved as a new dosage form. The plasma disposition pharmacokinetics of IVM tablets based on compressed zein microspheres after oral administration was studied over a 7-day period with six dogs (Canis familiaris), using a commercial IVM tablet (5 mg/piece, Yilijia(®) ) as a control. Clinical efficacy was tested using 270 dogs presented as veterinary patients for the treatment of demodicidosis. A formulation with disintegration time within 15 min could be obtained. The acquired C( max), T(max), and AUC were 9.89 ± 0.34 ng/mL, 11.33 ± 2.63 h, and 883.87 ng h/mL for IVM tablets based on compressed zein microspheres and 9.64 ± 1.05 ng/mL, 7.26 ± 2.09 h, and 666.30 ng h/mL for Yilijia(®), respectively. The bioavailability of the tablets based on compressed zein microspheres was 132.65% that of Yilijia( ®). Efficacy for the dogs in all the IVM tablets based on compressed zein microspheres-treated groups reached 100% at 7, 14, and 21 days post administration.