Farmaco (Societa chimica italiana : 1989)最新文献

{"title":"Derivative ultraviolet spectrophotometric determination of dexchlorpheniramine maleate in tablets in presence of coloring agents","authors":"Nilton S. Viana Jr.,&nbsp;Ligia M. Moreira-Campos,&nbsp;Cristina D. Vianna-Soares","doi":"10.1016/j.farmac.2005.08.009","DOIUrl":"10.1016/j.farmac.2005.08.009","url":null,"abstract":"<div><p>Formulation excipients can frequently affect the drug analysis in pharmaceuticals yielding background interference by ultraviolet spectrophotometry. Sample separation procedures to diminish such interferences are usually recommended as sample pre-treatment, however it can be difficult to eliminate them and they can still persist. In addition, these procedures can be time consuming and laborious to perform. Excipients, like dyeing agents can also be present in a formulation and yield color to drug solution. This work reports the successful development of a derivative ultraviolet spectrophotometry for dexchlorpheniramine maleate (DPM) determination in solid dosage forms, in spite of the color imparted to tablets solution. Standard curves obtained by second order derivative ultraviolet spectrophotometry showed linearity with a correlation coefficient of 0.9999 in the concentration range of 9.75–32.5 μg ml⁻¹ DPM in 0.1 mol l⁻¹<span> sulfuric acid, using zero-peak (ZP) and peak–peak (PP) methods. The average relative standard deviation range was between 0.26% and 1.08% and 0.18% and 0.63% for ZP and PP methods, respectively. Application of the method in tablet samples resulted in coefficients of variation in the range of 0.83–1.40%, and 0.63–0.83% for ZP and PP methods, respectively. Recovery test percentage values obtained were between 96.95% and 105.61% for the tested tablet samples.</span></p></div>","PeriodicalId":77128,"journal":{"name":"Farmaco (Societa chimica italiana : 1989)","volume":"60 11","pages":"Pages 900-905"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.farmac.2005.08.009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25638049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Absorption enhancement, mechanistic and toxicity studies of medium chain fatty acids, cyclodextrins and bile salts as peroral absorption enhancers","authors":"Pradeep Sharma,&nbsp;Manthena V.S. Varma,&nbsp;Harmander P.S. Chawla,&nbsp;Ramesh Panchagnula","doi":"10.1016/j.farmac.2005.08.008","DOIUrl":"10.1016/j.farmac.2005.08.008","url":null,"abstract":"<div><p><span>The objective of the present investigation was to evaluate an oral ‘drug delivery’ approach, which involves co-administration of absorption enhancers (AEs). The representative low permeable hydrophilic (biopharmaceutic classification system (BCS) Class III) drugs used in the study comprised of cefotaxime sodium<span><span> and ceftazidime pentahydrate, whereas low permeable lipophilic (BCS Class IV) drugs include </span>cyclosporin A<span><span><span> and lovastatin<span>. AEs from three different chemical classes, namely, medium chain fatty acids (sodium caprylate and caprate), </span></span>cyclodextrins<span> (β-cyclodextrin, hydroxypropyl β-cyclodextrin) and bile salts (sodium cholate and deoxycholate) were evaluated for absorption enhancement efficacy, mechanism of action and toxicity using in vitro everted intestinal sac model. These AEs were found to enhance </span></span>intestinal permeability of drugs from 2- to 27-fold. Light microscopy studies of intestinal sac incubated with AEs for 120 min revealed morphological changes in absorptive mucosa and rank order of toxicity were cyclodextrins</span></span></span> <!-->&gt;<!--> <!-->bile salts<!--> <!-->≅<!--> <span>medium chain fatty acids. Fluorescence polarization studies indicated that brush bordered membrane vesicles labeled with lipophilic (DPH, 12AS) and hydrophilic dyes (ANS), when treated with AEs exhibited concentration and time dependent decrease in fluorescence polarization. Total protein released in presence of AEs was more than control but considerably less than EDTA (0.58% w/v), which is known to cause toxic release of proteins from cell. Overall, AEs were found to significantly enhance drug permeability by decreasing lipid membrane fluidity and/or interacting with hydrophilic domains of membrane, and has the potential to improve oral delivery.</span></p></div>","PeriodicalId":77128,"journal":{"name":"Farmaco (Societa chimica italiana : 1989)","volume":"60 11","pages":"Pages 884-893"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.farmac.2005.08.008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25637054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New 8-substituted xanthiene derivatives as potent bronchodilators","authors":"Barkın Berk ,&nbsp;Hülya Akgün ,&nbsp;Kevser Erol ,&nbsp;Başar Sırmagül ,&nbsp;Zhan-Guo Gao ,&nbsp;Kenneth A. Jacobson","doi":"10.1016/j.farmac.2005.08.011","DOIUrl":"10.1016/j.farmac.2005.08.011","url":null,"abstract":"<div><p>The synthesis and structure determination of 8-aryl /alkyl aryl 1, 3-dimethyl-3, 7-dihydropurin-2, 6-dione derivatives <strong>(1-13)</strong><span><span><span>, was carried out in this study. Bronchodilator activity is investigated using isolated guinea-pig tracheal strips, pre-contracted by </span>acetylcholine and histamine. </span>Spasmolytic<span> activity of the compounds was compared to theophylline. Synthesized compounds </span></span><strong>(1-13)</strong> did not inhibit the acetylcholine-induced pre-contractions except compound <strong>(8)</strong> at 10⁻⁵ M concentration. In contrast, some of the compounds, especially <strong>(7)</strong>, <strong>(11)</strong>, <strong>(12)</strong> at 10⁻⁵ M and <strong>(3)</strong>, <strong>(4)</strong>, <strong>(9)</strong> and <strong>(11)</strong> in 10⁻⁴<span> M displayed inhibitory activity on the tracheal strips pre-contracted by histamine. The potency of the compounds at human adenosine receptors<span> was evaluated using radioligand binding assay and a cyclic AMP functional assay in CHO cells expressing these receptors. Compound </span></span><strong>(11)</strong> displayed the greatest activity against radioligand binding of specific agonists to A_2 A and A_2B receptors. The compounds were relatively selective for both A_2 A and A_2B compared with A₁ and A₃ receptors. All compounds were also tested for the inhibition of NECA-induced cAMP accumulation mediated by the A_2B adenosine receptor and compound <strong>(11)</strong><span> was found to be the most effective. Our results showed that these compounds are acting as selective adenosine antagonists, especially for adenosine A</span>_2B receptors, and are promising as potent anti-inflammatory agents rather than bronchodilator for the treatment of asthma.</p></div>","PeriodicalId":77128,"journal":{"name":"Farmaco (Societa chimica italiana : 1989)","volume":"60 11","pages":"Pages 974-980"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.farmac.2005.08.011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25673070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chiral resolution and binding study of 1,3,4,14b-tetrahydro-2,10-dimethyl-2H,10H-pyrazino[2,1-d]pyrrolo[1,2-b] [1,2,5]benzotriazepine (10-methyl-10-azaaptazepine) and 2-methyl-1,3,4,14b-tetrahydro-2H-pyrazino[2,1-d]pyrrolo[1,2-b] [1,2,5]benzothiadiazepine 10,10-dioxide (tiaaptazepine)","authors":"Gabriella De Martino ,&nbsp;Giuseppe La Regina ,&nbsp;Francesco La Torre ,&nbsp;Roberto Cirilli ,&nbsp;Ilario Mereghetti ,&nbsp;Alfredo Cagnotto ,&nbsp;Marino Artico ,&nbsp;Romano Silvestri","doi":"10.1016/j.farmac.2005.07.007","DOIUrl":"10.1016/j.farmac.2005.07.007","url":null,"abstract":"<div><p>The affinities of the enantiomers of 1,3,4,14b-tetrahydro-2,10-dimethyl-2<em>H</em>,10<em>H</em>-pyrazino[2,1-<em>d</em>]pyrrolo[1,2-<em>b</em>] [1,2,5]benzotriazepine (10-methyl-10-azaaptazepine, <strong>5</strong>) and 2-methyl-1,3,4,14b-tetrahydro-2<em>H</em>-pyrazino[2,1-<em>d</em>]pyrrolo[1,2-<em>b</em>] [1,2,5]benzothiadiazepine 10,10-dioxide (tiaaptazepine, <strong>6</strong>) were evaluated in receptor binding assays. Compound (+)-(S)-<strong>5</strong>, the most significant tested enantiomer, showed good affinities for 5-HT_1A, 5-HT_2A 5-HT_2C and α_2NA receptors, moderate affinities for DA₁, DA_3r and 5-HT₃ receptors and it was devoid of affinity for DA₂, α_1NA<span> and muscarinic receptors. Compound (+)-(S)-</span><strong>5</strong><span><span> showed an interesting pharmacological profile different from those of the reference compounds mirtazepine, </span>mianserin and 6-methoxymianserin.</span></p></div>","PeriodicalId":77128,"journal":{"name":"Farmaco (Societa chimica italiana : 1989)","volume":"60 11","pages":"Pages 931-937"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.farmac.2005.07.007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25636448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Syntheses, in vitro antibacterial and antifungal activities of a series of N-alkyl, 1,4-dithiines","authors":"F. Zentz ,&nbsp;R. Labia ,&nbsp;D. Sirot ,&nbsp;O. Faure ,&nbsp;R. Grillot ,&nbsp;A. Valla","doi":"10.1016/j.farmac.2005.06.015","DOIUrl":"10.1016/j.farmac.2005.06.015","url":null,"abstract":"<div><p>A series of dithiines were synthesized by cyclization of 4-(alkylamino)-4-oxobutanoic acids under the action of SOCl₂. Their in vitro antibacterial and antifungal activities have been evaluated against reference strains and versus reference compounds. The so-called ‘isoimides’ <strong>2a</strong>, <strong>2b</strong><span><span> were totally inactive whereas some imides had low </span>MICs for few bacteria and for few fungal microorganisms.</span></p></div>","PeriodicalId":77128,"journal":{"name":"Farmaco (Societa chimica italiana : 1989)","volume":"60 11","pages":"Pages 944-947"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.farmac.2005.06.015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25650413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of formulation and process variables on in vitro release of theophylline from directly-compressed Eudragit matrix tablets","authors":"A. Ceballos ,&nbsp;M. Cirri ,&nbsp;F. Maestrelli ,&nbsp;G. Corti ,&nbsp;P. Mura","doi":"10.1016/j.farmac.2005.07.002","DOIUrl":"10.1016/j.farmac.2005.07.002","url":null,"abstract":"<div><p><span>Extended-release theophylline (TP) matrix tablets were prepared by direct compression of drug and different pH-dependent (Eudragit L100, S100 and L100-55) and pH-independent (Eudragit RLPO and RSPO) polymer combinations. The influence of varying the polymer/polymer (w/w) ratio and the drug incorporation method (simple blend or solid dispersion) was also evaluated. Drug release, monitored using the Through Flow Cell system, markedly depended on both the kind of </span>Eudragit polymer combinations used and their relative content in the matrix. Maintaining a constant 1:1 (w/w) drug/polymers ratio, the selection of appropriate mixtures of pH-dependent and pH-independent polymers enabled achievement of a suitable control of TP release. In particular, matrices with a 0.7:0.3 w/w mixture of Eudragit L100-Eudragit RLPO showed highly reproducible drug release profiles, with an almost zero-order kinetic, and allowed 100% released drug after 360 min. As for the effect of the drug incorporation method, simple blending was better than the solid dispersion technique, which not only did not improve the release data reproducibility, but also caused, unexpectedly, a marked slowing down in drug release rate.</p></div>","PeriodicalId":77128,"journal":{"name":"Farmaco (Societa chimica italiana : 1989)","volume":"60 11","pages":"Pages 913-918"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.farmac.2005.07.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25272670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and biological evaluation of new thiazolyl/benzothiazolyl-amides, derivatives of 4-phenyl-piperazine","authors":"Christina Papadopoulou,&nbsp;Athina Geronikaki,&nbsp;Dimitra Hadjipavlou-Litina","doi":"10.1016/j.farmac.2005.06.014","DOIUrl":"10.1016/j.farmac.2005.06.014","url":null,"abstract":"<div><p>A series of thiazolyl-<em>N</em><span>-phenyl piperazines has been synthesised and tested for anti-inflammatory activity. Their </span><em>R</em>_M<span> values were determined as an expression of their lipophilicity. Theoretical calculation of their lipophilicity, as clog </span><em>P</em><span> and logPsk also performed. The effect of the synthesised compounds on inflammation, using the carrageenin<span> induced mouse paw oedema model was studied. In general, the studied compounds were found to be potent anti-inflammatory agents (44–74.1%). Anti-inflammatory activity was influenced by some structural characteristics of the synthesised compounds. An attempt was made to correlate their biological activity with some physicochemical parameters using a quantitative structure–activity relationship approach (QSAR).</span></span></p></div>","PeriodicalId":77128,"journal":{"name":"Farmaco (Societa chimica italiana : 1989)","volume":"60 11","pages":"Pages 969-973"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.farmac.2005.06.014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25207642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"INDEX AUTEURS 2005","authors":"","doi":"10.1016/S0014-827X(05)00213-2","DOIUrl":"https://doi.org/10.1016/S0014-827X(05)00213-2","url":null,"abstract":"","PeriodicalId":77128,"journal":{"name":"Farmaco (Societa chimica italiana : 1989)","volume":"60 11","pages":"Pages 981-984"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0014-827X(05)00213-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136587533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, analgesic activity and computational study of new isothiazolopyridines of Mannich base type","authors":"W. Malinka ,&nbsp;P. Świątek ,&nbsp;B. Filipek ,&nbsp;J. Sapa ,&nbsp;A. Jezierska ,&nbsp;A. Koll","doi":"10.1016/j.farmac.2005.08.005","DOIUrl":"10.1016/j.farmac.2005.08.005","url":null,"abstract":"<div><p><span>A series of new 4-arylpiperazine derivatives of isothiazolopyridine of Mannich base type and their non-4-arylpiperazine analogues (</span><strong>3</strong> and <strong>4</strong>) were synthesized and assayed as potential analgesic agents. Pharmacological assay demonstrated that all the compounds prepared, without exception, displayed significant activity in the mouse writhing assay. The analgesic action, expressed as ED₅₀<span>, was found to be 2–10 times more potent than that of acetylsalicylic acid and 1.5–10 times weaker than that of morphine, these being used as standards. The toxicities (LD</span>₅₀<span>) of the investigated derivatives varied and ranged from 250 to 2000 mg/kg. Additionally, the computational investigations were performed in order to find correlation between molecular structure and biological effects (toxicity, analgesic action) of discussed compounds. Useful model was found for toxicity assessment.</span></p></div>","PeriodicalId":77128,"journal":{"name":"Farmaco (Societa chimica italiana : 1989)","volume":"60 11","pages":"Pages 961-968"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.farmac.2005.08.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25637503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In situ and in vivo efficacy of peroral absorption enhancers in rats and correlation to in vitro mechanistic studies","authors":"Pradeep Sharma,&nbsp;Manthena V.S. Varma,&nbsp;Harmander P.S. Chawla,&nbsp;Ramesh Panchagnula","doi":"10.1016/j.farmac.2005.08.007","DOIUrl":"10.1016/j.farmac.2005.08.007","url":null,"abstract":"<div><p><span>The present investigation attempts to increase intestinal permeability<span> and hence absorption of biopharmaceutic classification system (BCS) Class III (cefotaxime sodium (CX)) and Class IV (cyclosporin A (CSA)) drugs by employing certain absorption enhancers. Drugs were co-perfused with sodium caprate (SC, 0.25% w/v), piperine<span> (P, 0.004% w/v) and sodium deoxycholate (SD, 1.0% w/v) separately in rat in situ single pass intestinal perfusion model. These additives increased intestinal permeability (</span></span></span><em>P</em>_app) and absorption rate constant (<em>K</em>_a) up to two and fourfold, respectively. SC exhibited substantial absorption enhancement of both CX and CSA, while SD and P enhanced absorption of CX and CSA, respectively. Co-administration of SC significantly enhanced <em>peroral</em> bioavailability of CX (from 29.4<!--> <!-->±<!--> <!-->1.7 to 69.6<!--> <!-->±<!--> <!-->3.2) and CSA (from 18.4<!--> <!-->±<!--> <!-->15.6 to 49.6<!--> <!-->±<!--> <!-->25.1) in rats, while P increased bioavailability of CSA (from 18.4<!--> <!-->±<!--> <!-->15.6 to 33.1<!--> <!-->±<!--> <!-->17.7). Transmission electron microscopy of intestinal mucosa revealed that SC and SD act on lipid and protein domains of absorptive membrane. P showed no effect on intestinal <em>P</em>_app<span><span> and oral bioavailability of CX but has a profound effect on CSA, a known P-glycoprotein (P-gp) substrate. These results indicated that P enhances intestinal absorption of CSA by modulating P-gp mediated efflux transport. Release of lactate dehydrogenase in situ from intestinal mucosa in the presence of absorption enhancer was taken as index of its local toxicity. All the absorption enhancers showed significantly less release of LDH compared to positive control, </span>sodium dodecyl sulfate<span> (60% w/v). Overall, the data indicate that the features of these commonly used food ingredients or endogenous bile salts can effectively improve bioavailability of various BCS Class III and Class IV drugs.</span></span></p></div>","PeriodicalId":77128,"journal":{"name":"Farmaco (Societa chimica italiana : 1989)","volume":"60 11","pages":"Pages 874-883"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.farmac.2005.08.007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25673069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}