Preparation and Characterization of the Emamectin Benzoate/Hydroxypropyl-B-Cyclodextrin Inclusion Complex

Abstract

The objective of this study was to prepare an inclusion complex of the insecticide emamectin benzoate (EB) with hydroxypropyl-β-cyclodextrin (HP-β-CD) by co-evaporation and spray drying methods. The complexation of both compounds was evaluated on the aqueous and solid state using phase solubility diagrams, differential scanning calorimetry (DSC), X-Ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The aqueous solubility of the inclusion complexes at pH 8 had a 2-fold increase respect to the drug alone and dissolution profiles showed a rise in the dissolution rate. These results suggest that the use of HP-β-CD could be an interesting alternative to enhance the bioavailability of EB in salmons.Key Words: Emamectin benzoate, cyclodextrin, inclusion complex, salmon.e-mail: cvonples@udec.cl 1.-INTRODUCTIONEmamectin benzoate, (4′'R)-4″-deoxy-4″-(methylamino)avermectin b1 benzoate, is one of the most widely used compounds in the salmon industry. Chemically, is a semisynthetic derivative of avermectins (Figure 1), which shows insecticide properties against the sea lice (Lepeophteirus salmonis), an ectoparasite that infests farmed salmons [1][2][3] . Unfortunately, it has been demonstrated that the efficacy of anti-infective treatments in salmons and trouts is low because is very difficult to control the dosage in medicated foods, which results in high intra-inter variability in plasma concentrations of the agents used [4][5][6] Of the approaches considered for improvement of the accuracy in the administration of EB, Glover et al. demonstrated that the intraperitoneal injection of the drug in farmed salmons resulted in higher and more predictable concentrations, but there are constraints that have relation with the manipulation of individual specimens 7 . From a point of view of the drug, one of the factors that influence the bioavailability of active compounds in living systems are their physicochemical properties like the solubility, which is often the limiting step in the absorption process. EB is a compound that has an erratic bioavailability and poor water solubility, which depends on the pH of the aqueous medium. At pH higher than 7, the solubility is drastically reduced and this is a relevant issue, because the intestinal pH of some fish can reach values of 7 -9 8 . Actually, the salmon industry is concerned about the need for optimize the therapeutic regimes, and one way to achieve predictable drug concentrations in plasma and tissues (taking into account the low and pH dependent solubility of EB) after an oral dose of a drug is improving its aqueous solubility with the use of cyclodextrins [9][10][11][12] . Of all the cyclodextrins used, hydroxypropyl-β-cyclodextrin (HP-β-CD) has been the most studied, because of its toxicological profile and better aqueous solubility [13][14][15] . Since there is no evidence of previous research, the aim of this work is to study the possibility of form an inclusion complex of EB and HP-β-CD, characterizing the...

Thermomechanical and Morphological Properties of Nanocomposite Films from Wheat Gluten Matrix and Cellulose Nanofibrils

“…Figure shows the FTIR spectrum of the CNF. The peaks in the fingerprint are assigned: 898 cm −1 to C–O–C stretching at β‐(1→4)‐glycosidic linkages (Kaushik and Singh ), 1158 cm −1 to C–O–C vibration in cellulose and hemicelluloses (Torres and others ), 1316 cm −1 to the symmetric CH 2 bending and wagging (Sun and others ), 1646 cm −1 to the OH bending of the adsorbed water (Oh and others ), 2900 cm −1 to the C–H stretching (Sun and others ).…”

Application of Solid Dispersion Technique to Improve Solubility and Sustain Release of Emamectin Benzoate

“…Its light-sensitivity leads to its facile degradation upon exposure to the sun, particularly in an alkaline environment, which greatly limits its biological activity in agricultural fields [5,6]. A lot of studies have been done in order to overcome its photodegradable disadvantage by preparing sustained release formulations using carboxymethyl chitosan, cellulose acetate butyrate, polydopamine- g -poly( N -isopropylacrylamide), polylactic acid, hydroxypropyl-β-cyclodextrin, and so on to modify EM [7,8,9,10,11]. Additionally, its poor solubility further limits its applications.…”