Synergetic taste masking of lipid coating and beta-cyclodextrin inclusion / 药学学报

Paracetamol was used as a model drug in this study to investigate the synergetic effects of lipid coating and beta-cyclodextrin (beta-CD) inclusion for masking the bitter taste of poorly soluble drugs. To control the concentration as low as possible of the free drug which produced a bitter taste, a kinetic model was established to calculate the drug distribution theoretically among the free drug in medium, lipid coated particles and molecular inclusion on the basis of the preparation and characterization of the lipid microspheres, so as to select the proper amount of beta-CD. Finally, the synergetic drug delivery systems were prepared and characterized by 1H nuclear magnetic resonance (1H NMR), molecular simulation and the electronic tongue. As a result, the drug release rate constant (k) of the lipid microspheres coated with octadecanol was determined as 0.001 270 s(-1). Then, the synergetic drug delivery systems were prepared with the ratio of 6.74 : 1 (w/w) for beta-CD and paracetamol. The chemical shift values for the fingerprint peaks of paracetamol all increased and hydrogen bonds were formed between the oxygen on the phenolic hydroxyl group, the nitrogen on the imino in paracetamol and the hydrogens on the hydroxyl groups in beta-CD. The results tested by the electronic tongue indicated that the paracetamol, lipid microspheres, beta-CD inclusion and their mixture showed different taste characteristics, with the bitterness order of the synergetic drug delivery systems approximately lipid microspheres < beta-CD inclusion < paracetamol, which confirmed the synergetic taste masking effects of lipid coating and beta-CD molecular inclusion. In summary, the synergetic taste masking was jointly achieved through the retard of the drug release by the lipid coating and the inclusion of the free paracetamol by beta-CD through hydrogen bonds.

Identification of the polymorphs of clopidogrel bisulfate based on the steric morphology parameters of crystals / 药学学报

The crystal form of solid substance had intrinsic correlation with its three dimensional crystal morphology. Based on the characterization of the three dimensional crystal morphology of clopidogrel bisulfate, this research is to establish a model based on the three dimensional morphological parameters. The granular samples composed of polymorphs of clopidogrel bisulfate and microcrystalline cellulose (MCC) were scanned by synchrotron radiation X-ray microscopic CT technology (SR-microCT) and the three dimensional structural models for which were constructed. Seven groups of three dimensional morphological parameters were calculated. Finally, the mathematical model was established with the multi-layer perception (MLP) artificial neutral network methods to identify and predict the polymorphs of clopidogrel bisulfate. The success rate of the model prediction for the polymorphs of clopidogrel bisulfate was 92.7% and the area under the ROC curve was 96.2%. The polymorphs of drugs could be identified and predicted through the numerical description of the three dimensional morphology. The volume, number of the vertices and the surface area were the major determinants for the identification of the polymorphs of clopidogrel bisulfate.

Intramuscular injection of naked plasmid DNA encoding human preproinsulin gene in streptozotocin-diabetes mice results in a significant reduction of blood glucose level / 生理学报

The insulin complement with gene therapy has been used as an experimental treatment for insulin dependent diabetes (IDDM). In the present study, we constructed naked plasmid DNA vector encoding recombinant human preproinsulin gene (pCMV-IN), and injected the plasmids (100 microg/mouse) intramuscularly combined with electroporation, to achieve the in vivo transfer of insulin gene in streptozotocin (STZ)-induced diabetic C57 mice. The expression of vector-derived insulin mRNA was detected with RT-PCR in transfected local skeletal muscles. The plasma insulin was elevated significantly in pCMV-IN injected diabetic C57 mice, which was complemented to the level similar to the intact normal control. The protein expression lasted for at least 35 days after the plasmid injection. Gene therapy with pCMV-IN plasmids considerably decreased the blood glucose level in STZ-induced diabetic mice from d 7 to d 35 by about 6 mmol/L. The gene therapy also reduced the mortality of severe diabetic mice significantly from 100% to 37% at the 6th week. Our results indicate that the direct intramuscular injection of naked plasmids encoding human preproinsulin gene achieves the effective expression of insulin. The restoration of insulin decreases blood glucose and increases the survival in severe diabetic mice. The gene therapy might be provided as a practical therapeutic approach to IDDM.