Wei-Feng Zhu

Process optimization, characterization and evaluation in vivo of oxymatrine-phospholipid complex.

The objective of this study was to prepare oxymatrine-phospholipid complex (OMT-PLC) to enhance oral bioavailability of oxymatrine. A central composite design approach was used for process optimization. The physicochemical properties of the complex obtained by optimal parameters were investigated by means of differential scanning calorimetry (DSC), X-ray diffraction (XRD) and N-octanol/water partition coefficient. Compared with those of the physical mixture or oxymatrine, the hepatocytes permeability of oxymatrine-phospholipid complexes was studied. The concentrations of oxymatrine after oral administration of OMT-PLC at different time in rats were determined by HPCE. Multiple linear regression analysis for process optimization revealed that the acceptable OMT-PLC was obtained wherein the optimal values of X(1), X(2) and X(3) were 3, 60 degrees C and 3 h, respectively. The oxymatrine and phospholipids in the OMT-PLC were combined by non-covalent bond, not forming a new compound. The better hepatocytes permeability was obtained by the OMT-PLC. Pharmacokinetic parameters of the complex in rats were T(max) 2.17 h, C(max) 0.437 microg ml(-1), AUC(0-infinity) 9.43 microg h ml(-1), respectively. The bioavailability of oxymatrine in rats was increased remarkably after oral administration of OMT-PLC (p<0.05), compared with those of oxymatrine or the physical mixture. This was mainly due to an improvement of the solubility of OMT-PLC.

Study on formability of solid nanosuspensions during nanodispersion and solidification: I. Novel role of stabilizer/drug property.

Few or no attempts have been made so far to understand the feasibility of solid nanosuspension formulation during nanodispersion and solidification in terms of drug properties and stabilizer characterizations. In order to establish a knowledge base about the effect of physicochemical property of drug compounds and stabilizers on solid nanosuspension production during nanodispersion and solidification, a comparative study was firstly performed on 10 different stabilizers at 3 concentrations for 8 structurally different drug compounds. Synthetic polymers (HPMC, PVP K30, CMS-Na and MC) displayed a poor stabilizing performance (10% success rate on average) during nanodispersion, but polymers showed better potential when higher concentrations was applied during freezing and lyophilization. Meanwhile, an effect for the surfactants group was even more pronounced during nanodispersion. However, the solid nanosuspension stabilized by surfactants showed the worst formability potential when be applied in setted concentrations during freezing and lyophilization. From the point of view of drug property, it was found that the surface hydrophobicity and cohesive energy of drug, were responsible for the formability of the solid nanosuspension during nanodispersion and solidification. Wetting index (k) and ΔE were concluded to have a direct correlation on the feasibility of formation of a stable solid nanosuspension, which can give a formulation design strategy from where candidate drugs and stabilizers with a set of properties.

Process optimization and evaluation of novel baicalin solid nanocrystals.

The objective of this study was to prepare baicalin solid nanocrystals (BCN-SNS) to enhance oral bioavailability of baicalin. A Box–Behnken design approach was used for process optimization. The physicochemical properties and pharmacokinetics of the optimal BCN-SNS were investigated. Multiple linear regression analysis for process optimization revealed that the fine BCN-SNS was obtained wherein the optimal values of homogenization pressure (bar), homogenization cycles (cycles), amount of TPGS to drug (w/w), and amount of MCCS to drug (w/w) were 850 bar, 25 cycles, 10%, and 10%, respectively. Transmission electron microscopy and scanning electron microscopy results indicated that no significant aggregation or crystal growth could be observed in the redispersed freeze-dried BCN-SNS. Differential scanning calorimetry and X-ray diffraction results showed that BCN remained in a crystalline state. Dissolution velocity of the freeze-dried BCN-SNS powder was distinctly superior compared to those of the crude powder and physical mixture. The bioavailability of BCN in rats was increased remarkably after oral administration of BCN-SNS (P < 0.05), compared with those of BCN or the physical mixture. The SNS might be a good choice for oral administration of poorly soluble BCN, due to an improvement of the bioavailability and dissolution velocity of BCN-SNS.

Preparation, characterization, and bioavailability of ursodeoxycholic acid-phospholipid complex in vivo.

The aim of this study was to prepare ursodeoxycholic acid–phospholipid complex (UDCA-PLC) to enhance oral bioavailability of UDCA, and the physicochemical properties of the complex were studied. Compared with those of UDCA tablet after oral administration in rats, the main pharmacokinetic characteristics and bioavailability of UDCA-PLC orally administered were evaluated. Tetrahydrofuran was used as a reaction medium, UDCA and phospholipids were resolved into the medium, and UDCA-PLC was formed after the organic solvent was evaporated off under vacuum condition. The physicochemical properties of the complex were evaluated using scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction, particle size distribution analysis, and n-octanol/water partition coefficient (P) study. The blood concentrations of UDCA-PLC and UDCA tablet at different time points after oral administration in rats were assayed by high-performance liquid chromatography (HPLC) after derivatization. The pharmacokinetic parameters were computed by software program 3p87. The X-ray diffraction and DSC studies showed that UDCA and phospholipids in the UDCA-PLC were combined by noncovalent bond, not forming a new compound, and n-octanol/water partition coefficient (P) of UDCA-PLC was effectively enhanced. The mean serum concentration–time curves of UDCA after oral administration of UDCA-PLC and UDCA tablet in rats were both in accordance with open two-compartment model. Pharmacokinetic parameters of UDCA tablet and the PLC in rats were Tmax 1.9144 and 1.5610 h, Cmax 0.0576 and 0.1346 μg/mL, and AUC0–∞ 4.736 and 11.437 μg h/mL, respectively. The bioavailability of UDCA in rats was significantly different (p < .05) compared with those of UDCA tablet after administration. The UDCA-PLC would be more prospective formulation in future.

Microcrystalline cellulose-carboxymethyl cellulose sodium as an effective dispersant for drug nanocrystals: A case study.

This study is aimed at seeking an alternative dispersant for spray drying of drug nanosuspensions. The ideal dispersant is not only able to prevent the agglomeration of drug nanocrystals in the suspension state, but also it is able to preserve redispersibility of drug nanocrystals after drying. An active pharmaceutical ingredient (API) was used as a model drug. API nanosuspensions were prepared by homogenization and converted into nanocrystals powder (API-NP) with microcrystalline cellulose-carboxymethyl cellulose sodium (MCCS) via spray drying. It was found that MCCS was able to prevent the aggregation of API-NP in the suspension state and the agglomeration during spray-drying process, possibility due to its high Zeta potential and steric barrier from network structure, and reduction of API size at nanoscale and incorporation into MCCS network structure did not affect the solid state of API as evidenced by DSC and XRD analysis. The spray-dried API-NP/MCCS powders exhibited excellent sphere-shape performance, and could easily redispersed to API-NC suspensions state. Dissolution of the spray-dried API-NP was distinctly superior to those of the crude powder and physical mixture, respectively. Within 30 min, approximate 85.87% of API was dissolved from the API-NP/MCCS. MCCS was demonstrated to be an effective dispersant for spray-dried drug nanocrystals and preservation of the nanocrystals associated with excellent redispersibility.

Process Optimization, Characterization, and Release Study In Vitro of an Intravenous Puerarin Lipid Micropheres Loaded with the Phospholipid Complex

A new formulation of puerarin lipid microspheres with the puerarin–phospholipid complex was prepared. A central composite design approach was used for process optimization in order to obtain the acceptable puerarin–phospholipid complex. The physicochemical properties of the complex obtained by optimal parameters were investigated by Fourier transform infrared spectrophotometry (FTIS). The physicochemical characterizations of puerarin lipid microspheres was evaluated. The release study in vitro of puerarin was studied by using microdialysis and pressure ultrafiltration technology. Multiple linear regression analysis for process optimization revealed that the acceptable puerarin–phospholipid complex was obtained wherein the optimal values of X1, X2, and X3 were 3, 60°C, and 3 hours, respectively. The FTIS studies of the complex demonstrated that puerarin and phospholipids were combined by non-covalent bonds, not form new compounds. The mean diameter and entrapment efficiency (%) were 171.35 and 87.94, respectively. The release of puerarin lipid microspheres could be evaluated by using microdialysis and ultrafiltration, but microdialysis seemed to be more suitable for the release study of puerarin lipid spheres. The drug release at three drug concentrations was initially rapid, but reached a plateau value within 30 minutes. Drug release of puerarin from the lipid microspheres occurred via burst release.

The Effect of Oil Components and Homogenization Conditions on the Physicochemical Properties of Zedoary Turmeric Oil Submicron Emulsions

Zedoary turmeric oil submicron emulsions were studied. The effects of the oil phase as a mixture (ternary) on the emulsion droplet size were investigated by means of the simplex lattice design. By optimizing the homogenization process and using only 1.2% soya lecithin, emulsions with 20% oil phase consisting of zedoary turmeric oil–MCT–soybean oil ratio of 0.5:0.25:0.25 with particle sizes in the range of 132–148 nm and moderate viscosity (3.6–4.0 mPa · s) could be prepared. These emulsions showed good stability over 6 months. This study showed the dominating influence of composition of the oil phase as well as the importance of the homogenizing conditions on processing and stability of the zedoary turmeric oil submicron emulsions.