Pharmacokinetics of Abamectin/Levamisole Combination in a Medium Chain Mono and Diglyceride-Based Vehicle and an In Vitro Release and In Vitro In Vivo Correlation Study for Levamisole.

A combination of lipophilic and hydrophilic drugs in a single solution is a challenge due to their different physicochemical properties. In vitro and in vivo release studies are useful to optimize this solution. The in vitro (Franz diffusion cell) release rate of levamisole phosphate from an isotropic vehicle of medium chain mono and diglycerides (MCMDG) was significantly slower than the release from water. The injectable solution of the isotropic MCMDG-based system was prepared with 13.65% of levamisole phosphate and 0.5% of abamectin. Two milliliters/50 kg (0.04 ml/kg) was injected subcutaneously into five healthy adult sheep. None of the animals showed the signs of inflammation at injection site. Both drugs were assayed using validated HPLC methods. The absorption rates for levamisole (0.71 ± 0.32 h-1) and abamectin (0.24 ± 0.08 day-1) from the MCMDG-based formulation were considerably slower than those of other studies conducted on the commercial products. The tmax was delayed for levamisole (2.20 ± 0.45 h) and abamectin (4.20 ± 1.64 days) compared with those in published studies. Longer MRT values for levamisole (6.14 ± 1.14 h) and abamectin (8.80 ± 1.39 days) were found in this study compared to those reported. A correlation was observed between in vivo fraction absorbed and in vitro fraction released for levamisole phosphate in the MCMDG-based formulation. The injection vehicle of isotropic MCMDG-based system delayed the subcutaneous absorption of levamisole phosphate and abamectin compared to the commercial subcutaneous injection products for levamisole and abamectin. Notably, this isotropic MCMDG-based vehicle system is prepared with a combination of two drugs with different physicochemical properties.

Isotropic systems of medium-chain mono- and diglycerides for solubilization of lipophilic and hydrophilic drugs.

The aim of this study was to investigate isotropic mono- and diglyceride-based (MCMDG) systems, which are potential vehicles for injectable products containing both hydrophilic and lipophilic drugs. For two-component systems, MCMDG was mixed with various masses of water. For three-component systems, the samples were prepared by mixing propylene glycol or glycerol formal or short-chain alcohols with MCMDG prior to the addition of water. The isotropic region was examined by visual inspection and confirmed using polarized light microscopy. Viscosities of formulations were measured. Solubilities of levamisole phosphate (hydrophilic) and abamectin (lipophilic) were determined in the isotropic formulations using high-performance liquid chromatography assay. The isotropic region in the two-component systems had a water content of up to 18% at 25 degrees C. Solvents such as propylene glycol (PG), glycerol formal (FG), and ethyl alcohol increased the isotropic region. The area of isotropic region in these three-component systems increased with increasing temperature. The area of the isotropic region became larger with decreasing dielectric constant and solubility parameter of the series of short-chain alcohols, except n-butyl alcohol, at 25 degrees C. The systems exhibited Newtonian behavior. The solubility of both hydrophilic and lipophilic drugs was high in formulations at 25 degrees C. It was concluded that more water was solubilized in MCMDG/short-chain alcohols/water systems, and the isotropic region in the short-chain alcohol systems enlarged compared with MCMDG/PG/water or MCMDG/GF/water systems, except the n-butyl alcohol system. Hydrophilic and lipophilic drugs solubilize in the systems. The isotropic formulations containing MCMDG may represent an alternative to more traditional formulations for injectable formulations containing both lipophilic and hydrophilic drugs.

Isotropic medium chain mono-diglyceride/oil/water formulations for solubilization of lipophilic and hydrophilic drugs.

The aim of the study was to investigate isotropic mono- and diglyceride (MCMDG)/oil/water systems as vehicles for combinations of hydrophilic and lipophilic drugs. For two-component systems, MCMDG was mixed with various masses of water. For MCMDG/oily vehicles/water systems, mixtures were prepared by mixing oil and MCMDG prior to the addition of the appropriate masses of water. The isotropic region was examined by visual inspection and confirmed using polarized light microscopy. Viscosities of the systems were determined. Solubilities of hydrophilic (levamisole HCl) and lipopohilic (abamectin) drugs were determined in the isotropic formulations by HPLC analysis. The isotropic regions in the two-component and three-component systems had water contents of up to 18% at 25 degrees C. The isotropic formulations exhibited Newtonion flow. The viscosity of formulations having the same percentage of water increased with increasing ratio of MCMDG to oil in three-component systems. The solubilities of the levamisole HCl and abamectin were higher in the isotropic MCMDG/sesame oil/water formulations than in equivalent MCMDG/water formulations. In some formulations, the solubility of levamisole HCl was higher in the absence of abamectin than in combination with abamectin. Isotropic MCMDG/oil/water systems were obtained without the use of co-surfactants. Increasing water content in the system did not proportionally increase the solubility of hydrophilic drug. Solubilization of hydrophilic drug was affected by lipophilic drug in the presence or absence of SO and lipophilic drug solubility was affected by hydrophilic drug in the absence of SO. These systems are suitable vehicles to deliver both hydrophilic and lipophilic drugs and could be of interest for pharmaceutical formulations.