Determination of the Dissolution/Permeation and Apparent Solubility for Microencapsulated Emamectin Benzoate Using In Vitro and Ex Vivo Salmo salar Intestine Membranes

Pharmaceuticals

José Miguel Troncoso¹  José Ricardo Pérez-Correa²  Victoria Molina²  Wendy Franco²  Carlos von Plessing³  Alex Romero⁴  Sergio Benavides⁵ 

[1] Cargill Innovation Center, Cargill, Calbuco 5570130, Chile;Department of Chemical and Bioprocess Engineering, Pontificia Universidad Católica de Chile, Santiago 6904411, Chile;Faculty of Pharmacy, Universidad de Concepción, Concepción 4030000, Chile;Laboratory of Immunology and Stress of Aquatic Organisms, Animal Pathology Institute, Universidad Austral de Chile, Valdivia 5090000, Chile;Research Center in Agri-Food and Applied Nutrition, Universidad Adventista de Chile, Chillán 3820572, Chile;

关键词: emamectin benzoate;    dissolution/permeation;    release kinetics;    apparent solubility;    apparent permeability;    uptake;   

DOI  :  10.3390/ph15060652

来源: DOAJ

【 摘 要 】

In this work, two microencapsulation techniques were used to protect and improve the absorption of emamectin benzoate (EB), which is an antiparasitic drug used to control Caligus rogercresseyi. EB has a low aqueous solubility, which affects its absorption in the intestine of Salmo salar. Microparticles were produced by spray drying and ionic gelation, using Soluplus^® (EB–SOL) and sodium alginate (EB–ALG) as polymers, respectively. Studies were conducted on dissolution/permeation, apparent permeability (Papp), apparent solubility (Sapp), and absorption using synthetic and biological membranes. Based on these results, the amount of EB in the microparticles needed to achieve a therapeutic dose was estimated. The EB–ALG microparticles outperformed both EB–SOL and free EB, for all parameters analyzed. The results show values of 0.45 mg/mL (80.2%) for dissolution/permeation, a Papp of 6.2 mg/mL in RS–L, an absorption of 7.3% in RS, and a Sapp of 53.1% in EM medium. The EB–ALG microparticles decrease the therapeutic dose necessary to control the parasite, with values of 3.0⁻² mg/mL and 1.1⁻² mg/mL for EB in EM and RS, respectively. The Korsmeyer–Peppas kinetic model was the best model to fit the EB–ALG and EB–SOL dissolution/permeation experiments. In addition, some of our experimental results using synthetic membranes are similar to those obtained with biological membranes, which suggests that, for some parameters, it is possible to replace biological membranes with synthetic membranes. The encapsulation of EB by ionic gelation shows it is a promising formulation to increase the absorption of the poorly soluble drug. In contrast, the spray-dried microparticles produced using Soluplus^® result in even less dissolution/permeation than free EB, so the technique cannot be used to improve the solubility of EB.

【 授权许可】

Unknown