Reduction of bitterness of antihistaminic drugs by complexation with β-cyclodextrins

Reduction of bitterness of antihistaminic drugs by cyclodextrin (CyD) complexation was examined. The stability constant (Kc) of the 1:1 CyD inclusion complexes with antihistaminic drugs increased in the order of 2-hydroxypropyl-β-CyD (HP-β-CyD) ≈ β-CyD > γ-CyD > α-CyD for diphenhydramine and epinastine, and HP-β-CyD ≈ β-CyD > α-CyD > γ-CyD for hydroxyzine, cetirizine, and dl-chlorpheniramine. The inclusion complexes inhibited the adsorption of antihistaminic drugs to lipid membrane using liposomes, as the magnitude of Kc increased. From human gustatory sensation tests, β-CyD and HP-β-CyD potently suppressed the bitterness of antihistaminic drugs in a dose-dependent manner. Further, an artificial taste sensor analysis revealed that β-CyD and HP-β-CyD inhibited the bitterness of antihistaminic drugs in solution. The results suggest that CyDs suppress the bitterness of antihistaminic drugs in solutions through the formation of inclusion complexes. These results may provide useful information for masking or elimination of bitterness of drugs using CyDs.     

Evaluation of antibacterial activity of caffeic acid encapsulated by β-cyclodextrins

Abstract

Context: Caffeic acid is described as antibacterial, but this bioactive molecule has some issues regarding solubility and stability to environmental stress. Thus, encapsulation devices are required. Objective: The aim of this work was to study the effect of the caffeic acid encapsulation by cyclodextrins on its antibacterial activity. Materials and methods: The interactions between the caffeic acid and three cyclodextrins (β-cyclodextrin (βCD), 2-hydroxypropyl-β-cyclodextrin (HPβCD) and methyl-β-cyclodextrin were study. Results and discussion: The formation of an aqueous soluble inclusion complex was confirmed for βCD and HPβCD with a 1:1 stoichiometry. The βCD/caffeic acid complex showed higher stability than HPβCD/caffeic acid. Caffeic acid antibacterial activity was similar at pH 3 and pH 5 against the three bacteria (K. pneumoniae, S. epidermidis and S. aureus). Conclusions: The antibacterial activity of the inclusion complexes was described here for the first time and it was shown that the caffeic acid activity was remarkably enhanced by the cyclodextrins encapsulation.     

Polymorphism of miconazole during preparation of solid systems of the drug and β-cyclodextrins

Kneading and coevaporate procedures were used in an endeavour to prepare cyclodextrin inclusion complexes of the antimycotic drug miconazole. Crystalline miconazole was present in the preparations containing β-cyclodextrin. A kneading product of miconazole and hydroxypropyl-β-cyclodextrin, molar ratio 1:2, was amorphous. It might be a genuine inclusion complex or more probably a mixture of amorphous miconazole and amorphous hydroxypropyl-β-cyclodextrin. The antimycotic effect of the amorphous kneading product was tested against a strain of Candida albicans in a fluid medium. The product had a fungicidal effect whereas a physical mixture of miconazole and hydroxypropyl-β-cyclodextrin only inhibited the growth of the fungus. The kneading product had an effect which was similar to the effect of the water-soluble miconazole nitrate salt.It was observed during the study that commercially available miconazole from different manufacturers contained at least two different crystal forms of the drug.     

Inclusion complexation of glisentide with α-, β- and γ-cyclodextrins

Complexation of glisentide with α-, β- and γ-cyclodextrin (CD) has been investigated in aqueous solution and in the solid state. Complex formation in solution has been analysed using solubility diagrams and NMR spectroscopy and the interaction in solid state has been studied by X-ray diffractometry, DSC and IR spectroscopy. The thermodynamic parameters, ΔH°, ΔS° and ΔG°, of complexation with β- and γ-CD have been calculated from the temperature dependence of the stability constant. The process has been found to be exothermic and ΔS° is slightly unfavourable. In addition, it has been found that the ionization state of glisentide plays an important role in complexation and the fact that the extent of complexation is greater with β- than with γ-CD has revealed the importance of the cavity size to get an adequate fitting between host and guest molecules. The inclusion of the ortho-substituted aromatic ring of glisentide has been evidenced by NMR spectroscopy. Finally, complexes have been prepared by coprecipitation and kneading methods and it has been found that the former is more suitable to achieve solid-state complexation.     

Specificity evaluation of antibodies against human β3-adrenoceptors

β(3)-Adrenoceptors are a promising drug target for the treatment of urinary bladder dysfunction, but knowledge about their expression at the protein level and their functional role is limited, partly due to a lack of well validated tools. As many antibodies against G-protein-coupled receptors, including those against β(3)- and other β-adrenoceptor subtypes, lack selectivity for their target, we have evaluated the specificity of five antibodies raised against the full-length protein of the human β(3)-adrenoceptor (H155-B01), its N-terminus (LSA4198 and TA303277) and its C-terminus (AB5122, Sc1472) in immunoblotting and immunocytochemistry. Our primary test system were Chinese hamster ovary cells stably transfected to express each of the three human β-adrenoceptor subtypes at near physiological levels (100-200?fmol/mg protein). None of the five antibodies exhibited convincing target specificity in immunoblotting with Sc1472 apparently being least unsuitable. In immunocytochemistry, LSA4198 and Sc1472 appeared most promising, exhibiting at least some degree of specificity. As these two antibodies have been raised against different epitopes (N- and C-terminus of the receptor, respectively), we propose that concordant staining by both antibodies provides the most convincing evidence for β(3)-adrenoceptor labelling in cyto- or histochemistry studies.     

An evaluation on potential anti-inflammatory effects of β-lapachone

Inflammation plays a significant role in the pathogenesis of chronic diseases. Inflammatory diseases such as bacterial diseases, Alzheimer's disease, rheumatoid arthritis, multiple sclerosis, and so on, impose huge costs on the health systems. On the other hand, some side effects have been reported for the classic drugs used to treat these diseases. Plants phytochemicals have revealed important prospects in the handling and controlling of human diseases. β-lapachone, is a derivative of the naturally occurring element lapachol, from Tabebuia avellanedae and its anti-inflammatory effects have been reported in several reports. This review summarized the evidence from cell and animal studies supporting the anti-inflammatory role of β-lapachone and discussed its potential mechanisms.     

Adsorption characterization of various modified β-cyclodextrins onto TEMPO-oxidized cellulose nanofibril membranes and cryogels

TEMPO-Oxidized cellulose nanofibrils (toCNF), in the form of highly entangled network such as membrane or cryogels, have proven to be of interest for various applications, including drug release or purification by pollutant adsorption. β-Cyclodextrins (β-CDs) have the ability to form inclusion complexes with large amount of hydrophobic molecules, and are considered as a promising way to bring new functionalities to these materials, by reducing drug burst release effect or improving the pollutant adsorption properties. The study of the adsorption β-CDs onto toCNF is then crucial to design toCNF/β-CDs materials, but is very complex due to the chemical proximity between these compounds. In this study, we develop toCNF cryogels containing various types of β-CDs derivatives by physical adsorption. Different protocols for analyzing the interactions between these compounds, such as Isothermal Titration Calorimetry (ITC), Quartz-Crystal Microbalance with dissipation monitoring (QCM-d) and a Phenolphthalein-based protocol (PhP protocol) have been performed. Adsorption between β-CD and toCNF was proven at two different temperatures with ITC. QCM-d measurements allowed measuring adsorption of different β-CDs derivatives onto toCNF, with higher adsorption measured for the modified β-CDs, and with estimated binding capacity ranging from 13.4 to 47.6 μmol/g toCNF. PhP protocol allowed us to monitor the amount of β-CDs released in aqueous environment, highlighting a lower release for modified β-CDs onto toCNF, and the results were consistent with the estimated binding capacity. This quantification of the binding adsorption capacity of various β-CDs is key results for optimizing the design of toCNF/β-CDs materials.     

Journal of Chinese Pharmaceutical Sciences

ＪｏｕｒｎａｌｏｆＣｈｉｎｅｓｅＰｈａｒｍａｃｅｕｔｉｃａｌＳｃｉｅｎｃｅｓＩｎｓｔｒｕｃｔｉｏｎｓＴｏＡｕｔｈｏｒｓ—１９９８１．Ｔｈｉｓｊｏｕｒｎａｌｉｓａｗｏｒｌｄｗｉｄｅｄｉｓｔｒｉｂｕｔｅｄｊｏｕｒｎａｌｏｆｐｈａｒｍａｃｅｕｔｉｃａｌｓｃ...     

Journal of Chinese Pharmaceutical Sciences

InstructionsToAuthors-20001.Thisjournalisaworldwidedistributedjournalofpharmaceuticalsciencesincludingmedicinalchemistry,phytochemistry,pharmacognosy,pharmaceuticalanalysis,pharmaceuticsandpharmacology.Thejournalpublishespapersofthefollowingcategories:originalresearcharticles,shortcommunications,reviewsonvariousaspectsanddevelopmentsinspecifiedareasofpharmaceuticalresearch,aswellasbookreviews,introductionofnewdrugsandnewsinbriefThemainpurposeofissuingthisjournalistointroducerecentdevelopments…     

Journal of Chinese Pharmaceutical Sciences

1．Thisjournalisaworldwidedistributedjournlalofpharmaceuticalsciencesincludingmedicinalchemistry，phytochemistry，pharmacognosy，pharmaceuticalanalysis，pharmaceuticsandpharmacology．Thejournalpublishespapersofthefollowingcategories：originalresearcharticles，shortcommunications，reviewsonvariousaspectsanddevelopmentsinspecifiedareasofpharmaceuticalresearch，aswellasbookreviews,introductionofnewdrugsandnewsinbrief.Themainpurposeofissuingthisjournalistointroducerecentdevelopmentsandachievements…     

Pharmacokinetic evaluation of β-caryophyllene alcohol in rats and beagle dogs

1.?β-caryophyllene alcohol (BCPA) has shown therapeutic promise in the treatment of asthma and inflammation with low toxicity. The aim of the current study was to report the pharmacokinetic profiles of BCPA in rats and dogs.

2.?Following intravenous administration, BCPA exhibited moderate volumes of distribution (V_z) ranging from 5.63 to 8.97?L/kg in rats and low V_z (2.89?±?1.12?L/kg) in dogs. Systemic plasma clearance was high in both species, resulting in a short elimination half-life ranging from 29.6 to 48.3?min. In rats, the intravenous pharmacokinetics was dose dependent. The measured oral bioavailability was low in rats for BCPA solution (1.17?±?0.78%), suspension (1.21?±?0.33%) and PEG formulation (6.22?±?2.63%). The bioavailability was lower in dogs for BCPA solution (0.12?±?0.05%) and PEG formulation (0.25?±?0.07%), indicating significant species difference. However, treatment of plasma samples with β-glucuronidase increased the systematic exposure of BCPA as assessed from AUC _(0-∞) by 24.7- or 2.62-fold in rats and dogs, respectively, which suggested glucuronidation was a significant metabolic pathway for BCPA possibly due to first-pass metabolism.

3.?In summary, this was the first preclinical pharmacokinetic investigation of BCPA in animals, providing vital knowledge for further preclinical research and subsequent clinical trials.     

Journal of Chinese Pharmaceutical Sciences

Instructions to Authors———20061.This journal is a worldwide distributed journal of pharmaceutical sciences including medicinal chemistry,phytochemistry, pharmacognosy, pharmaceutical analysis, pharmaceutics and harmacology. The journal publishespapers of the following categories: original research articles, short communications, reviews on various aspects anddevelopments in specified areas of pharmaceutical research, as well as book reviews, introduction of newdrugs andnews in brief. The ma…