Development and Optimization of Intravenous Puerarin Emulsions Formation by a Novel Complex-Phase Inversion-Homogenization Technology

Abstract

Puerarin is naturally isoflavone C-glycoside which was isolated from Pueraria lobota. It is traditionally used to reduce febrile symptoms and decrease myocardial consumption of oxygen, and it also can increase coronary artery blood flow and improve microcirculation. [1][2][3] Due to poor oral bioavailability, the commercial product puerarin i.v. is widely used in clinical. It is used for treatment of coronary artery disease, ischemic heart disease, cerebrovascular disease, coronarism and cerebral angio spasm in clinic. 4,5) But the clinical efficacy of puerarin i.v. is limited by severe and acute toxic side effects, such as intravenous hemolysis. So it is very necessary to seek a novel delivery system for puerarin in order to reduce its side effects. 6,7) Submicron emulsion, also referred to as lipid emulsions or lipid microspheres, is potentially interesting drug delivery system.8) It can reduce drug hydrolysis and increase drug bioavailability.9) By means of incorporating drug into the lipophilic core (of the oil droplets or in the core of micelles) or in the interface, direct contact of the drug with the body fluid and tissues can also be avoided in order to minimize the drug possible side effects. The reports about the ability of these systems to enhance the efficacy and to reduce side effects have appeared in the literature. 10) And there are some drug loaded emulsions for i.v. injection on the market such as amphotericin B, 11) prostaglandin E 1 . 12)Puerarin is slightly soluble in water (the aqueous solubility of about 4 mg/ml) and poorly soluble in oil.13) So it would be very difficult to incorporate puerarin into oil phase of emulsion by the traditional homogenization method. The puerarin emulsions are not possibly prepared by applying the simple method which was to dissolve the drug in the oil in order to prepare the emulsion. The objectives of this study are: (a) puerarin emulsion was firstly prepared by novel complexphase inversion-homogenization (CPIH) technology which was a technology basically combining drug phospholipid complex with the phase inversion-homogenization technology, and to investigate if it was possible to decrease the particle size, span of dispersity and to increase entrapment efficiency of puerarin emulsion; (b) to optimize preparative parameters which powerfully affect the characteristics of puerarin emulsion by central composite design; (c) to evaluate the physicochemical character of puerarin emulsion such as morphology and stability. ExperimentalMaterials Puerarin was obtained from Xian-guochui Ltd., purity 99.5% (Xi-AN, China). Egg lecithin was purchased from Hua-qing-mei-hen Ltd. (Beijing, China); Purified soybean oil for parenteral use (Tieling BeiYa Pharmaceutical Co., Tieling, China). Synperonic F68 (BASF AG, Ludwigshafen, Germany), All other chemicals and reagents were of analytical or chromatographic grade.Component of Preparation Formula Puerarin, 1 g; soybean lecithin, 1.2 g; soybean oil, 12 g; synperonic F68, 0.2 g; glycerol, 2.5 g; a-tocopherol, 300 mg; double disti...

Process optimization and evaluation of novel baicalin solid nanocrystals

“…19 Box-Behnken design has been comprehensively adopted to optimize the process of formulations. [20][21][22][23] Those studies demonstrated the apparent advantage of Box-Behnken design utilization in the formulaoptimization process.…”

In-vivo pharmacokinetics, tissue distribution and anti-tumour effect of hydroxycamptothecin delivered in oil-in-water submicron emulsions

“…The entrapment efficiency (EE %) was determined according to a previously described method [17] . Briefly, the emulsions with drugs were centrifuged at 23 000 rpm for 1 h (4°C) in a Hermle ultracentrifuge (Hermle, Germany) to separate the incorporated drug and the non‐incorporated drug.…”

“…The entrapment efficiency (EE %) was determined according to a previously described method. [17] Briefly, the emulsions with drugs were centrifuged at 23 000 rpm for 1 h (4°C) in a Hermle ultracentrifuge (Hermle, Germany) to separate the incorporated drug and the non-incorporated drug. The concentrations of HCPT in the emulsion (n1) and free drug in the aqueous (the non-incorporated drug) (n2) were assayed by HPLC after dilution with methanol.…”

Nanoemulsões como sistemas de liberação parenteral de fármacos

“…77 Entretanto, outras técnicas mais precisas têm sido descritas, como a centrifugação, que exige a validação do tempo (que pode ser teoricamente calculado) e da velocidade de centrifugação, de forma a garantir que somente os cristais livres precipitem, em totalidade, para serem posterioremente lavados, dissolvidos em solvente adequado e quantificados. 48,70,78 Alguns autores têm utilizado também a cromatografia em coluna Sephadex, visando a separação das frações contendo o fármaco livre e associado, para posterior quantificação por cromatografia de alta eficiência. 12,55 Existem ainda as técnicas que se baseiam na passagem do fár-maco livre através de membranas de tamanho de poro conhecido: a ultrafiltração/centrifugação, que é a mais utilizada, e a microdiálise.…”