Evaluation of CoQ10 solubility in different pharmaceutically acceptable excipients

GLUJOY M; ZAPICO V; CONTIN MARIO; TRIPODI VALERIA; BREGNI C; CARLUCCI A

Encuentro; 1º Encuentro Internacional de Ciencias Farmceuticas; 2010

Introduction The mitochondrial respiratory chain disorders are the most common kind of hereditary neurometabolic diseases. Ubiquinone (CoQ10), is a very important component in the oxidative phosphorylation. It is well known that its bioavailability depends mostly on the drug release system used, formulations containing dissolved drug are the most bioavailable ones (1) (2). The objective of the work was to evaluate its solubility in different pharmaceutically acceptable excipients (oil phases and surfactants). Afterwards, binary mixtures were prepared with different excipients ratios and their capacity of CoQ10 solubilization was evaluated. Materials and methods Materials: Ubicaderone (2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone); liquid petroleum jelly, Dicaprylic ether, Propylene Glycol Caprylate, Isopropyl myristate, Glyceryl Caprylate/Caprate, Caprylic/Capric Triglyceride, Lecithin, castor oil; Polyoxyethylene (20) sorbitan monooleate, Caprylocaproyl macrogol-8-glycerides,  Polyoxyl (40) hydrogenated castor oil, Polyoxyethylene (6) C9-C11 alcohol, Polyoxyethylene (6.5) C13 alcohol  and Laureth-4. Methods: To determine the equilibrium solubility, drug in excess was added to excipients. The samples were left to equilibrate using a Rotating Bottle apparatus and then filtered. Binary mixtures were prepared with the four oil phases and the two surfactants which had shown the best values of solubility and in 1:2; 1:1; 2:1 weight ratios. Samples were analyzed by HPLC (Waters, USA). Results The excipients which showed the most efficiency in drug solubility were: Caprylic/Capric Triglyceride,  Dicaprylic Ether, Propylene Glycol Caprylate  and isopropyl myristate (82.98 to 173,06 mg/g);    Polyoxyethylene (6.5) C13 alcohol (HLB 11) and Laureth-4 (HLB 9.7) were able to solubilize 15.94 and 63.55 mg/g, respectively. As polar and dispersion forces of selected excipients were similar every evaluated mixture ratios generated homogeneous system. The binary mixtures exhibited the best capacity of solubilization. Conclusions  Lipid-based drug delivery systems are of increasing interest because of their potential to solubilize drug that may be otherwise difficult to develop (3). Isopropyl myristate showed the highest value of CoQ10 solubilization which is promising data for biopharmaceutical evaluation, because it has a parameter solubility similar to cell membranes. A number of binary mixtures able to solubilize a clinical amount of drug were obtained without any instabilization sign during a month at room temperature of storage. These results encourage further studies for CoQ10 oral administration in soft capsules.