Showing papers in "Acta Pharmaceutica in 2014"
TL;DR: Gels prepared with medium molecular mass chitosan might be effectively used for different antifungal agents in the treatment of vaginal candidiosis, since it has high mucoadhesiveness, suitable mechanical and release properties with good vaginal retention.
Abstract: The aim of the present study was to evaluate chitosan as a vaginal mucoadhesive gel base for econazole nitrate and miconazole nitrate. To this aim, different types of chitosan with different molecular masses and viscosity properties [low molecular mass chitosan (viscosity: 20,000 mPa s), medium molecular mass chitosan (viscosity: 200,000 mPa s), high molecular mass chitosan (viscosity: 800,000 mPa s)] have been used. First, rheological studies were conducted on chitosan gels. Mechanical, syringeability and mucoadhesive properties of chitosan gels were determined. Release profiles of econazole nitrate and miconazole nitrate from chitosan gels were obtained and evaluated kinetically. In addition, anticandidal activities of formulations were determined. Finally, vaginal retention of chitosan gels in rats was evaluated by in vivo distribution studies. Based on the results, it can be concluded that gels prepared with medium molecular mass chitosan might be effectively used for different antifungal agents in the treatment of vaginal candidiosis, since it has high mucoadhesiveness, suitable mechanical and release properties with good vaginal retention.
71 citations
TL;DR: Data obtained in the study suggest that the butanol fraction derived from the ethanolic extract of K. senegalensis root possessed excellent antioxidative as well as α-glucosidase and a-amylase inhibitory activities while chromones and/or p-anilinophenol could be the main bioactive compounds responsible for the observed activities.
Abstract: This study evaluated the in vitro antioxidative activity of Khaya senegalensis extracts and inhibitory effects of some solvent fractions on α-glucosidase and α-amylase activities. The stem bark, root and leaf samples of the plant were sequentially extracted with ethyl acetate, ethanol and water and then tested for antioxidative activity. Our findings revealed that the ethanolic extract of the root had the highest antioxidative activity. Solvent-solvent fractionation of the root ethanolic extract yielded a butanol fraction that showed higher antioxidative activity than other fractions. Furthermore, the butanol fraction had significantly higher (p < 0.05) α-glucosidase and α-amylase inhibitory activities with IC50 values of 2.89 ± 0.46 and 97.51 ± 5.72 μg mL⁻¹, respectively. Enzyme kinetic studies indicated that the butanol fraction is a non-competitive inhibitor for α-glucosidase with an inhibition binding constant K(i) of 1.30 μg mL⁻¹ and a competitive inhibitor of α-amylase with a K(i) of 7.50 μg mL⁻¹. GC-MS analysis revealed that the butanol fraction contained two chromones, p-anilinophenol and 3-ethyl-5-(3-ethyl-(3H)-benzothiazol-2-ylidene)-2-(p-tolylvinylamino)-4-thiazolidinone. Data obtained in the study suggest that the butanol fraction derived from the ethanolic extract of K. senegalensis root possessed excellent antioxidative as well as α-glucosidase and a-amylase inhibitory activities while chromones and/or p-anilinophenol could be the main bioactive compounds responsible for the observed activities.
67 citations
TL;DR: Therapeutic drug monitoring (TDM) of antipsychotic drugs is the specific method of clinical pharmacology, which involves measurement of drug serum concentrations followed by interpretation and good cooperation with the clinician.
Abstract: Schizophrenia is a severe psychiatric disorder often associated with cognitive impairment and affective, mainly depressive, symptoms. Antipsychotic medication is the primary intervention for stabilization of acute psychotic episodes and prevention of recurrences and relapses in patients with schizophrenia. Typical antipsychotics, the older class of antipsychotic agents, are currently used much less frequently than newer atypical antipsychotics. Therapeutic drug monitoring (TDM) of antipsychotic drugs is the specific method of clinical pharmacology, which involves measurement of drug serum concentrations followed by interpretation and good cooperation with the clinician. TDM is a powerful tool that allows tailor-made treatment for the specific needs of individual patients. It can help in monitoring adherence, dose adjustment, minimizing the risk of toxicity and in cost-effectiveness in the treatment of psychiatric disorders. The review provides complex knowledge indispensable to clinical pharmacologists, pharmacists and clinicians for interpretation of TDM results.
58 citations
TL;DR: A novel series of thiophenes having biologically active sulfonamide 2-11, 3-methylisoxazole 12, 4-methoxybenzo[d] thiazole 13, quinoline 14, 15, benzoylphenylamino 16, and anthracene-9,10-dione 17 moieties were prepared and showed cytotoxic activities compared to doxorubicin as a positive control.
Abstract: A novel series of thiophenes having biologically active sulfonamide 2-11, 3-methylisoxazole 12, 4-methoxybenzo[d] thiazole 13, quinoline 14, 15, benzoylphenylamino 16, and anthracene-9,10-dione 17 moieties were prepared. Structures of the newly synthesized compounds were established by elemental analysis and spectral data. All newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Most of the screened compounds showed cytotoxic activities compared to doxorubicin as a positive control. Compounds 6, 7, 9 and 13 (IC50 values 10.25, 9.70, 9.55 and 9.39 μmol L-1) revealed higher cytotoxic activities than that of doxorubicin (IC50 = 32.00 μmol L-1). Also, compounds 5, 8 and 10 were found nearly as active as doxorubicin (IC50 28.85, 23.48 and 27.51 μmol L-1).
53 citations
TL;DR: Screening extracts of Eastern European medicinal plants for novel components that target bacterial cells and their quorum sensing (QS) communication systems confirmed that multicomponent anti-infectious mechanisms are used by plants, which may be useful for drug development.
Abstract: The objective of this study was to screen extracts of twenty Eastern European medicinal plants, using wild-type and reporter Chromobacterium violaceum bioassays, for novel components that target bacterial cells and their quorum sensing (QS) communication systems. Three types of activity and their combinations were revealed: (i) direct antimicrobial growth-inhibitory activity, (ii) non-specific and specific pro-QS activities, (iii) anti-QS activity. Among seven plant extracts showing direct growth-inhibitory activity, the strongest effect was shown by Arctostaphylos uva-ursi (bearberry) leaves. Many plants stimulated violacein production by wild-type C. violaceum ATCC 31532 in a non-specific manner, and only the herb Bidens tripartita (three-lobe beggarticks) contained compounds that mimic acyl-homoserine lactone and operated as a QS agonist. Anti-QS activity was found in eleven plants including Quercus robur (oak) cortex, Betula verrucosa (birch) buds and Eucalyptus viminalis (Manna Gum) leaves. Subsequent statistical analysis showed differences between antimicrobial and anti-QS activities, whereas both activities were defined by phylogenetic position of medical resource plant. Finally, extract from Quercus robur cortex revealed at least two fractions, showing different anti-QS mechanisms. These data confirm that multicomponent anti-infectious mechanisms are used by plants, which may be useful for drug development.
49 citations
TL;DR: It was found that with increased stirring speed, the PVA concentration or the use of ethyl acetate had a significantly negative effect on encapsulation efficiency, which had an adverse effect on the burst effect.
Abstract: The main objective of this study was to evaluate the influ ence of the formulation and process parameters on PLGA microparticles containing a practically insoluble model drug (ibuprofen) prepared by the o/w solvent evaporation method Multivariate data analysis was used The effects of altered stirring speed of a mechanical stirrer (600, 1000 rpm), emulsifier concentrations (PVA concentration 01 %, 1 %) and solvent selection (dichloromethane, ethyl acetate) on microparticle characteristics (encapsulation efficiency, drug loading, burst effect) were observed It was found that with increased stirring speed, the PVA concentration or the use of ethyl acetate had a significantly negative effect on encapsulation efficiency In addition, ethyl acetate had an adverse effect on the burst effect, while increased stirring speed had the opposite effect Drug load was not affected by any particular variable, but rather by the interactions of evaluated variables
44 citations
TL;DR: Addition of the lubricant, magnesium stearate, during the blending process improved the content uniformity of blends containing the filler with larger particles, which seems to be caused by reduced sampling error due to the suppression of electrostatic charge.
Abstract: The article describes the development and production of tablets using direct compression of powder mixtures. The aim was to describe the impact of filler particle size and the time of lubricant addition during mixing on content uniformity according to the Good Manufacturing Practice (GMP) process validation requirements. Processes are regulated by complex directives, forcing the producers to validate, using sophisticated methods, the content uniformity of intermediates as well as final products. Cutting down of production time and material, shortening of analyses, and fast and reliable statistic evaluation of results can reduce the final price without affecting product quality. The manufacturing process of directly compressed tablets containing the low dose active pharmaceutical ingredient (API) warfarin, with content uniformity passing validation criteria, is used as a model example. Statistic methods have proved that the manufacturing process is reproducible. Methods suitable for elucidation of various properties of the final blend, e.g., measurement of electrostatic charge by Faraday pail and evaluation of mutual influences of researched variables by partial least square (PLS) regression, were used. Using these methods, it was proved that the filler with higher particle size increased the content uniformity of both blends and the ensuing tablets. Addition of the lubricant, magnesium stearate, during the blending process improved the content uniformity of blends containing the filler with larger particles. This seems to be caused by reduced sampling error due to the suppression of electrostatic charge.
39 citations
TL;DR: The emulsion represents a suitable vehicle for topical delivery of EGCG and permeated into the deeper region of human stratum corneum was significantly larger for the o/w emulsion compared to the gel.
Abstract: The aim of the study was to examine the effect of topical vehicles on the in vivo human stratum corneum penetration of the antioxidant and skin photoprotective agent (-)-epigallocatechin-3-gallate (EGCG). Model oil-in-water (o/w) emulsion and gel formulations containing 1 % (m/m) EGCG were prepared and subjected to photodegradation studies in order to select excipients that minimize the light instability of EGCG. The optimized emulsion and gel were applied to human volunteers and the EGCG percutaneous permeation was evaluated in vivo by the tape- -stripping technique. No significant differences in the percentage of the applied EGCG dose diffused into the stratum corneum were observed between the o/w emulsion (36.1 ± 7.5 %) and gel (35.5 ± 8.1 %) preparations. However, the amount of EGCG permeated into the deeper region of human stratum corneum was significantly larger for the o/w emulsion compared to the gel. Therefore, the emulsion represents a suitable vehicle for topical delivery of EGCG.
27 citations
TL;DR: The results demonstrated that the proposed HPLC method is applicable in the quality control of combined pharmaceutical tablets containing IRB and HCT and the accuracy of the proposed method was > 97 %.
Abstract: A simple, sensitive and accurate HPLC method with high throughput has been developed and validated for the simultaneous determination of irbesartan (IRB) and hydrochlorothiazide (HCT) in combined pharmaceutical dosage forms. The proposed method employed, for the first time, a monolithic column in the analysis. Optimal chromatographic separation of the analytes was achieved on Chromolith(®) Performance RP-18e column using a mobile phase consisting of phosphate buffer (pH 4)/acetonitrile (50:50, V/V) pumped isocratically at a flow rate of 1.0 mL min(-1). The eluted analytes were monitored with a UV detector set at 270 nm. Under the optimum chromatographic conditions, linear relationship with a good correlation coefficient (R ≥ 0.9997) was found between the peak area and the corresponding concentrations of both IRB and HCT in the ranges of 10-200 and 1-20 ng mL(-1). The limits of detection were 2.34 and 0.03 ng mL(-1) for IRB and HCT, respectively. The intra- and inter-assay precisions were satisfactory as the RSD values did not exceed 3 %. The accuracy of the proposed method was > 97 %. The proposed method had high throughput as the analysis involved a simple procedure and a very short run-time of < 3 min. The results demonstrated that the method is applicable in the quality control of combined pharmaceutical tablets containing IRB and HCT.
23 citations
TL;DR: Results show that LIG/HP-β-CD complexation can be of great use for increasing the stability and biological efficacy of LIG.
Abstract: To improve the stability and oral bioavailability of Z-ligustilide (LIG), the inclusion complex of LIG with hydroxypropyl- β-cyclodextrin (HP-β-CD) was prepared by the kneading method and characterized by UV-Vis spectroscopy, differential thermal analysis (DTA) and Fourier transform infrared (FTIR) spectroscopy. LIG is capable of forming an inclusion complex with HP-b-CD and the stoichiometry of the complex was 1:1. Stability of the inclusion complex against temperature and light was greatly enhanced compared to that of free LIG. Further, oral bioavailability of LIG and the inclusion complex in rats were studied and the plasma drug concentration-time curves fitted well with the non-compartment model to estimate the absolute bioavailability, which was 7.5 and 35.9 %, respectively. In conclusion, these results show that LIG/HP-β-CD complexation can be of great use for increasing the stability and biological efficacy of LIG.
18 citations
TL;DR: This extract of Coreopsis tinctoria flowering tops showed higher scavenging activity of ABTS and hydroxyl radical activity than rutin, however not in the DPPH test, suggesting that CTFT possess antioxidant and free radical scavenging potentials.
Abstract: The aim of the present study was to determine the antioxidant activity of Coreopsis tinctoria flowering tops (CTFT). Studies were conducted to obtain suitable extraction conditions for chlorogenic acid, quercetin, luteolin, apigenin and kaempferol, which were identified and quantified by HPLC. Response surface methodology was employed to optimise the ultrasound-assisted extraction conditions including extraction time, ethanol concentration and liquid-solid ratio. The antioxidant activity of the extracts was analysed using various antioxidant models, such as DPPH, ABTS and hydroxyl radical scavenging assay. CTFT extracted for 15.0 min with ethanol at a concentration of 60.4% and with liquidsolid ratio 27.5:1 possessed a considerable amounts of total flavonoids and polyphenols (18.9%). This extract showed higher scavenging activity of ABTS and hydroxyl radical activity than rutin, however not in the DPPH test. We may assume that CTFT possess antioxidant and free radical scavenging potentials.
TL;DR: Consumption of EGCG during DOX therapy seems to be safe and beneficial, since E GCG does not decrease DOX anticancer efficacy and could ameliorate DOX hepatotoxicity.
Abstract: Catechins may influence both desirable and undesirable effects of many drugs. In this study, the in vitro effect of (+)-catechin, (-)-epicatechin, (-)-epigallocatechin, (-)-epicatechin gallate, and (-)-epigallocatechin gallate (EGCG) on the efficacy of anticancer drug doxorubicin (DOX) was studied in HCT-8 cancer cells. Rat hepatocytes were used to study the influence of EGCG on DOX hepatotoxicity. Cell proliferation and viability were studied by 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyl tetrazolium bromide and neutral red uptake test assays. Formation of reactive oxygen species (ROS) was determined using the dichlorofluorescein assay. All of the studied catechins (1-25 μmol L(-1)) had no effect on the proliferation of intestinal cancer cells and did not affect the antiproliferative effect of DOX (1-8 μmol L(-1)) in these cells. Moreover, EGCG at 25 μmol L(-1) increased the viability of isolated hepatocytes and significantly protected these cells against DOX-induced toxicity and ROS production. Consumption of EGCG during DOX therapy seems to be safe and beneficial, since EGCG does not decrease DOX anticancer efficacy and could ameliorate DOX hepatotoxicity.
TL;DR: Three different series of phosphonate derivatives synthesized using the addition and/or addition-cyclization protocol of Horner-Wadsworth-Emmons reagents showed remarkable antitumor activity against breast and prostate carcinoma cell lines, whereas a moderate to good effect on ovarian and liver cancer cells was observed.
Abstract: Three different series of phosphonate derivatives, β-amino- and fused thiadiazolo/thiadiazine-phosphonates have been synthesized using the addition and/or addition-cyclization protocol of Horner-Wadsworth-Emmons (HWE) reagents to 1,2,4-triazole-3-thiols. The design of potentially antimicrobial and anticancer phosphor esters relied on the results of computer-assisted molecular modeling. All synthesized phosphonates were evaluated for their in vitro antimicrobial activities while anticancer properties were determined for eight out of twenty new phosphonates. The tested phosphonates, except for compounds that have a nitrile moiety, exhibited moderate to significant antimicrobial activity. Nevertheless, the most active compounds were fused thiadiazole-phosphonates, which inhibited the growth of both Gram-negative and Gram-positive bacteria better than β-aminophosphonates and fused thiadiazolophosphonates. In parallel, the antitumor activity screenings of selected phosphonates from each series and substrate 1 were also done. Their antitumor properties against ten carcinoma cell lines, including breast (MCF7, MDA-MB- 231/ ATCC, MDA-MB-435, BT-549), ovarian (IGROVI, OVCAR-3, SK-OV-3), prostate (PX-3, PU-145), and liver (HEPG2), were investigated. The results showed that all synthesized compounds reflected remarkable antitumor activity against breast (especially MDA-MB-231/ATCC and BT-549), and prostate carcinoma cell lines (PC-3 and DU-145), whereas a moderate to good effect on ovarian and liver cancer cells was observed.
TL;DR: Diclofenac decreased cell viability under Hypoxia and inflammatory conditions and increased the secretion of VEGF induced by LPS and hypoxia.
Abstract: Diclofenac belongs to non-steroidal anti-inflammatory drugs (NSAIDs) and non-selective COX inhibitors. The aim of this study was to examine the effect of diclofenac on endothelial cell proliferation under the influence of hypoxia or inflammatory conditions. Another goal was to check whether diclofenac modulates the secretion of angiogenic factors such as VEGF and bFGF in human microvascular endothelial cells (HMEC-1) in the presence of CoCl2 or lipopolysaccharide (LPS), which could influence the endothelial cells in an autocrine manner or other cells in a paracrine manner. HMEC-1 cells were treated with 0.1 and 0.3 mmol L-1 diclofenac in the presence of 100 μg mL-1 LPS or 200 μmol L-1 CoCl2. Diclofenac decreased cell viability under hypoxia and inflammatory conditions. The stimulation of bFGF secretion by LPS in microvascular endothelial cells (HMEC-1 cell) was attenuated by diclofenac. Diclofenac increased the secretion of VEGF induced by LPS and hypoxia.
TL;DR: Three sensitive, accurate and precise spectrofluorimetric methods were developed for fast quantitative analysis of gemifloxacin mesylate and linezolid in pharmaceutical formulations and were validated and successfully applied for determination of the cited drugs in tablets.
Abstract: Quinone-based fluorophores and enhanced native fluorescence techniques were applied for a fast quantitative analysis of gemifloxacin mesylate (GEM) and linezolid (LIN) in pharmaceutical formulations. For this purpose, three sensitive, accurate and precise spectrofluorimetric methods were developed. GEM, as an n-electron donor, reacts with 7,7,8,8-tetracyanoquinodimethane (method A) and 2,5-dichloro-3,6-dihydroxy-p-benzoquinone (method B) as п-electron acceptors, forming charge transfer complexes that exhibit high fluorescence intensity at 441 and 390 nm upon excitation at 260 and 339 nm, respectively. Method C depends on measurement of enhanced native fluorescence of LIN in phosphate buffer (pH 5) at 380 nm upon excitation at 260 nm. Experimental factors affecting fluorescence intensity were optimized. Linearity was obtained over concentration ranges 50-500, 10-60 and 20-400 ng mL-1 for methods A, B and C, respectively. The developed methods were validated and successfully applied for determination of the cited drugs in tablets.
TL;DR: Correlation analysis based on chromatograms and pharmacological activities found that salvianolic acid B, tanshinol and protocatechuic aldehyde were active components of SMI because they were correlated to antioxidant properties.
Abstract: Correlation analysis based on chromatograms and pharmacological activities is essential for understanding the effective components in complex herbal medicines. In this report, HPLC and measurement of antioxidant properties were used to describe the active ingredients of Salvia miltiorrhiza injection (SMI). HPLC results showed that tanshinol, protocatechuic aldehyde, rosmarinic acid, salvianolic acid B, protocatechuic acid and their metabolites in rat serum may contribute to the efficacy of SMI. Assessment of antioxidant properties indicated that differences in the composition of serum powder of SMI caused differences in vascular endothelial cell protection. When bivariate correlation was carried out it was found that salvianolic acid B, tanshinol and protocatechuic aldehyde were active components of SMI because they were correlated to antioxidant properties.
TL;DR: It is demonstrated that this essential oil can be used in the formulation of personal care products and is effective in inhibiting the growth of the main bacteria responsible for bad perspiration odor.
Abstract: This study evaluated the effectiveness of the essential oil of Pimenta pseudocaryophyllus in inhibiting the growth of the main bacteria responsible for bad perspiration odor (Staphylococcus epidermidis, Proteus hauseri, Micrococcus yunnanensis and Corynebacterium xerosis). The chemical profile of the essential oil was evaluated by high-resolution gas chromatography (HR-GC) and four constituents were identified, eugenol being the major component (88.6%). The antimicrobial activity was evaluated by means of the turbidimetric method, using the microdilution assay. The minimum inhibitory concentration (MIC) values of the essential oil ranged from 500 to 1,000 μg mL⁻¹. Scanning electron microscope (SEM) observations confirmed the physical damage and morphological alteration of the test bacteria treated with the essential oil, reference drugs and eugenol. The findings of the study demonstrated that this essential oil can be used in the formulation of personal care products.
TL;DR: Based on the docking results, the CRMYPC ligand has sufficient hydrogen bonding interactions with residues of the active side of neuraminidase-1 and can be therefore proposed as a potential inhibitor of neuraminaidases-1.
Abstract: It is critical to seek potential alternative treatments for H1N1 infections by inhibiting neuraminidase-1 enzyme. One of the viable options for inhibiting the activity of neuraminidase-1 is peptide drug design. In order to increase peptide stability, cyclization is necessary to prevent its digestion by protease enzyme. Cyclization of peptide ligands by formation of disulfide bridges is preferable for designing inhibitors of neuraminidase-1 because of their high activity and specificity. Here we designed ligands by using molecular docking, drug scan and dynamics computational methods. Based on our docking results, short polypeptides of cystein-arginine-methionine-tyrosine-proline-cysteine (CRMYPC) and cysteine-arginine-aspargine-phenylalanine-proline-cysteine (CRNFPC) have good residual interactions with the target and the binding energy DGbinding of –31.7402 and –31.0144 kcal mol–1 ,r espectively. These values are much lower than those of the standards, and it means that both ligands are more accessible to ligand-receptor binding. Based on drug scan results, both of these ligands are neither mutagenic nor carcinogenic. They also show good oral bioavailability. Moreover, both ligands show relatively stable molecular dynamics progression of RMSD vs. time plot. However, based on our metods, the CRMYPC ligand has sufficient hydrogen bonding interactions with residues of the active side of neuraminidase-1 and can be therefore proposed as a potential inhibitor of neuraminidase-1.
TL;DR: The enteric coating using Eudragit L30D-55 could protect probiotics from the acidic gastric environment and enhance the bioactivity of probiotics along with replacement of pathogenic microbes in human intestine.
Abstract: In the present study, a capsule formulation composed of enteric coated granules of Lactobacillus acidophilus ATCC 4962 was developed using Eudragit L30D-55 as enteric polymer. Optimization of the capsule formulation was achieved with a maximum viable cell count after 2 h of incubation in acid medium and disintegration time of 1 h in buffer pH 6.8. The amount of Eudragit L30D-55 in the capsules correlated with gastric juice resistance. The best protective qualities against artificial gastric juice were observed when capsules were prepared from granules composed of L. acidophilus, corn starch, lactose monohydrate, polyvinylpyrrolidone and coated with 12.5 % (m/V) of Eudragit L30D-55. Capsule formulation of L. acidophilus in edible broth medium suspension serves as a cheap alternative to the expensive freeze-drying procedure for preparing L. acidophilus. In addition, the enteric coating using Eudragit L30D-55 could protect probiotics from the acidic gastric environment and enhance the bioactivity of probiotics along with replacement of pathogenic microbes in human intestine.
TL;DR: The seasonal phytochemical variation and the antimicrobial potential of V. zizanioides roots collected in Brazil are described and some extracts showed promising antimicrobial effects.
Abstract: This paper describes the seasonal phytochemical variation and the antimicrobial potential of V. zizanioides roots collected in Brazil. Considering the high levels of chemical constituents and their biological activity in dichloromethane fraction, the plants were grown in different seasons and the respective dichloromethane fractions were analyzed by gas chromatography-mass spectrometry. The antimicrobial activity was evaluated against several pathogenic microorganisms by determining the minimum inhibitory concentration (MIC) using the agar dilution method. Yields of dichloromethane fractions from plants collected in the autumn and spring occurred in a higher proportion than in other seasons. Khusimol (2) was isolated by column chromatography and identified by NMR and CG-MS, along with other sesquiterpenes, including β-vetivenene (1), vetiselinenol (3), isovalencenol (4), vetivenic acid (5), α-vetivone (6) and β-vetivone (7). Some extracts showed promising antimicrobial effects, with MICs ranging from 31.25 to 500 μg mL-1. Kushimol was slightly active against the tested microorganisms.
TL;DR: Serum GST was not associated with GST genotypes and COPD or smoking history in the authors' study subjects, and the GSTP1 mutant genotype of exon 5 (GG), as well as GSTP 1 mutant and heterozygous genotypes ofExon 6 (TT and CT), were suggested to be genetic contributors to COPD susceptibility.
Abstract: The aim of this study was to test the hypothesis that glutathione-S-transferase (GST) genotypes were associated with COPD. GSTP1, GSTM1 and GSTT1 genotypes were determined by DNA methods and GST activity spectrophotometrically in older male Caucasian Croats (non-smokers, ex-smokers, and smokers) with stable COPD (n = 30) and sex/age matched controls (n = 60). The distribution of GSTP1 genotypes and alleles in controls vs. COPD showed a statistical difference (p < 0.05). The odds ratio of CC/CT+TT (wild type GSTP1 exon 6 vs. joint heterozygous and mutant homozygous GSTP1 exon 6) was 10.000 and statistically different (p = 0.002). In this study, the GSTP1 mutant genotype of exon 5 (GG), as well as GSTP1 mutant and heterozygous genotypes of exon 6 (TT and CT), were suggested to be genetic contributors to COPD susceptibility. Null GSTM1, null GSTT1 and joint GSTM1/GSTT1 null genotypes were not disease associated. Serum GST was not associated with GST genotypes and COPD or smoking history in our study subjects. Conclusions drawn from the study should be further supported and clarified by studies with larger sample sizes.
TL;DR: Comparison in vitro ciprofloxacin solubility and dissolution studies were performed in the reactive media containing aluminium hydroxide, calcium carbonate or zinc sulphate, indicating that small volume dissolution experiments can be useful for biorelevant dissolution tests.
Abstract: Ciprofloxacin bioavailability may be reduced when ciprofloxacin is co-administered with metallic ion containing preparations. In our previous study, physicochemical interaction between ciprofloxacin and ferrous sulphate was successfully simulated in vitro. In the present work, comparative in vitro ciprofloxacin solubility and dissolution studies were performed in the reactive media containing aluminium hydroxide, calcium carbonate or zinc sulphate. Solid phases collected from the dissolution vessel with aluminium hydroxide, calcium carbonate and zinc sulphate were investigated for their properties. The results obtained indicate that different types of adducts may form and retard ciprofloxacin solubility and dissolution. In the case of aluminium, no phase changes were observed. The solid phase generated in the presence of calcium carbonate was identified as hydrated ciprofloxacin base. Similarly to iron, a new complex consistent with Zn(SO4)2(Cl)2(ciprofloxacin)2 × nH2O stoichiometry was generated in the presence of relatively high concentrations of ciprofloxacin hydrochloride and zinc sulphate, indicating that small volume dissolution experiments can be useful for biorelevant dissolution tests.
TL;DR: The release pattern indicated strict control of drug release both under gastric and intestinal conditions, suggesting the potential advantage of using a solid dispersion of drug-Eudragit S 100 to overcome the problem of dose dumping after the rupture of the pH dependent alginate gels.
Abstract: Alginate vehicles are capable of forming a gel matrix in situ when they come into contact with gastric medium in the presence of calcium ions. However, the gel structure is pH dependent and can break after gastric emptying, leading to dose dumping. The aim of this work was to develop modified in situ gelling alginate formulations capable of sustaining dextromethorphan release throughout the gastrointestinal tract. Alginate solution (2 %, m/m) was used as a vehicle for the tested formulations. Solid matrix of the drug and Eudragit S 100 was prepared by dissolving the drug and polymer in acetone. The organic solvent was then evaporated and the deposited solid matrix was micronized, sieved and dispersed in alginate solution to obtain candidate formulations. The release behavior of dextromethorphan was monitored and evaluated in a medium simulating the gastric and intestinal pH. Drug-polymer compatibility and possible solid-state interactions suggested physical interaction through hydrogen bonding between the drug and the polymer. A significant decrease in the rate and extent of dextromethorphan release was observed with increasing Eudragit S 100 concentration in the prepared particles. Most formulations showed sustained release profiles similar to that of a commercial sustained-release liquid based on ion exchange resin. The release pattern indicated strict control of drug release both under gastric and intestinal conditions, suggesting the potential advantage of using a solid dispersion of drug-Eudragit S 100 to overcome the problem of dose dumping after the rupture of the pH dependent alginate gels.
TL;DR: Investigation of the effect of natural and synthetic substances on the expression level of genes encoding transporters present in the blood-brain barrier suggested that herbs can play an important role in overcoming the BBB and multidrug resistance to pharmacotherapy of brain cancer and mental disorders.
Abstract: There are a number of compounds that can modify the activity of ABC (ATP-binding cassette) and SLC (solute carrier) transporters in the blood-brain barrier (BBB). The aim of this study was to investigate the effect of natural and synthetic substances on the expression level of genes encoding transporters present in the BBB (mdr1a, mdr1b, mrp1, mrp2, oatp1a4, oatp1a5 and oatp1c1). Our results showed that verapamil caused the greatest reduction in the mRNA level while other synthetic (piracetam, phenobarbital) and natural (codeine, cyclosporine A, quercetin) substances showed a selective inhibitory effect. Further, the extract from the roots of Panax ginseng C. A. Meyer exhibited a decrease of transcription against selected transporters whereas the extract from Ginkgo biloba L. leaves resulted in an increase of the expression level of tested genes, except for mrp2. Extract from the aerial parts of Hypericum perforatum L. was the only one to cause an increased mRNA level for mdr1 and oatp1c1. These findings suggest that herbs can play an important role in overcoming the BBB and multidrug resistance to pharmacotherapy of brain cancer and mental disorders, based on the activity of selected drug-metabolizing enzymes and transporters located in the BBB.
TL;DR: Non-effervescent floating tablets were prepared with a combination of optimized solid dispersions and release retarding polymers/swellablepolymers such as xanthan gum and polyethylene oxide using swellable polymers.
Abstract: The objective of the study was to enhance the solubility of carvedilol phosphate and to formulate it into non-efferves cent floating tablets using swellable polymers. Solid disper sions (SD) of carvedilol were prepared with hydrophilic carriers such as polyvinylpyrrolidone and poloxamer to enhance solubility. Non-effervescent floating tablets were prepared with a combination of optimized solid dispersions and release retarding polymers/swellable polymers such as xanthan gum and polyethylene oxide. Tablets were evaluated for physicochemical properties such as hardness, thickness and buoyancy. SD prepared with the drug to poloxamer ratio of 1:4 by melt granulation showed a higher dissolution rate than all other dispersions. Formulations containing 40 mg of polyethylene oxide (C-P40) and 50 mg xanthan gum (C-X50) were found to be best, with the drug retardation up to 12 hours. Optimized formulations were characterized using FTIR and DSC and no drug and excipient interactions were detected.
TL;DR: It is demonstrated that administration of hydrophilic statin with sildenafil results in reduction of pulmonary vascular remodeling and right ventricular pressure, which may suggest that statins play a positive role in right ventricle function or the process of angiogenesis in pulmonary hypertension development.
Abstract: There is considerable interest in the pleiotropic effects of statins and their potential role in the treatment of pulmonary hypertension. Previous experimental findings indicate that a combination of lipophilic statins with phosphodiesterase type-5 inhibitor, sildenafil, can offer preventive effects on rat monocrotaline-induced pulmonary hypertension. The present study is aimed to assess whether therapeutic regimen provides any benefits. Seven days after pulmonary hypertension induction, hydrophilic rosuvastatin and sildenafil were given for 14 days to male Wistar outbred rats. Right ventricular pressure, right ventricle mass and three biomarkers were evaluated after 21 days: brain natriuretic peptide, high-density lipoprotein cholesterol and vascular endothelial growth factor. The present study demonstrates that administration of hydrophilic statin with sildenafil results in reduction of pulmonary vascular remodeling and right ventricular pressure. The results of biochemical measurements may suggest that statins play a positive role in right ventricle function or the process of angiogenesis in pulmonary hypertension development.
TL;DR: It was concluded that simple solutions of T in the presence of DMSO and TPGs were more promising systems for effective transdermal permeation compared to gel, emulsion or oleaginous systems.
Abstract: Tocopherol represents a big challenge for transdermal permeation owing to its extreme hydrophobicity and large mole cular mass. The aim of the present study was to develop alpha-tocopherol (T) topical formulations and evaluate their ex vivo and in vivo permeation. Franz diffusion cells were used for ex vivo permeation, and neonatal rats were used for in vivo permeation. Seven gel formulations and 21 liquid formulations were investigated for physical stability, viscosity and permeation of T. Analysis of T was performed by a validated HPLC method using a UV detector. The ex vivo permeation from gel and emulsion formulations was very poor (0.001–0.015 %). Highest permeation was observed from monophasic liquid formulations containing dimethyl sulfoxide (DMSO), tocopheryl polyethylene glycols (TPGs), propylene glycol, ethanol and 9.5 % T. The in vivo results demonstrated higher retention in the epidermis compared to subcutaneous tissues, 1377 and 1.13 µg g –1 , respectively. Increasing T concentration from 4.8 to 9.5 % did not increase the amount permeated or % of T retained. It was concluded that simple solutions of T in the presence of DMSO and TPGs were more promising systems for effec tive transdermal permeation compared to gel, emulsion or oleaginous systems.
TL;DR: The aim of this study was to formulate and evaluate the stability of syrups with candesartan cilexetil and valsartan extemporaneously prepared using commercial tablets (Diovan® and Atacand®).
Abstract: Available tablets or capsules for adults are often used to prepare extemporaneously formulated medicines appropriate for children. The most acceptable drug forms in pediatric population are oral liquids and pharmacists use commercial dispersing media to compound syrups from an active substance or from tablets available on the market. In many countries ready-to-use dispersing media are not available or refunded, but pharmacists can use other compounded media, providing their compatibility and stability are proven. The aim of this study was to formulate and evaluate the stability of syrups with candesartan cilexetil (1 mg mL-1) and valsartan (4 mg mL-1) extemporaneously prepared using commercial tablets (Diovan® and Atacand®). The following three different suspending media, which could be easily made in a pharmacy, were investigated: V1 - with xanthan gum (0.5 %), V2 - the USP/NF vehicle for oral solution and V3 - the medium based on a simple sucrose syrup. The stability of preparations was studied during 35 days of storage in a dark place at controlled temperature of 25 and 4 °C. During the study, microscopic observation was carried out and pH, viscosity, and concentration of candesartan cilexetil and valsartan were analyzed. Syrups with valsartan prepared with V2 and V3 media were stable for 3 or 4 weeks when stored at 25 °C, while syrups with candesartan were stable for as long as 35 days. For syrups prepared using V1 medium, the 14-day expiry date was not achieved because of microbial deterioration.
TL;DR: The development and validation of a new microwell-based spectrophotometric assay for determination of olmesartan medoxomil (OLM) in tablets offers a reduction in the exposure of analysts to the toxic effects of organic solvents, as well as a Reduction in the cost of analysis.
Abstract: The study describes the development and validation of anew microwell-based spectrophotometric assay for de-termination of olmesartan medoxomil (OLM) in tablets.The formation of a colored charge-transfer (CT) complexbetween OLM as an n-electron donor and 2,3-dichloro--5,6-dicyano-1,4-benzoquinone (DDQ) as a
TL;DR: Crystallization of the drug entacapone from binary solvent mixtures was monitored in situ using a Raman optical probe and results have shown that the presence of a particular polymorph is strongly dependent on the nature and portion of the solvent in the binary solvent mixture.
Abstract: Crystallization of the drug entacapone from binary solvent mixtures was monitored in situ using a Raman optical probe The recorded Raman spectra and statistical analysis, which included the principal components method and indirect hard modeling made it possible to estimate the starting point of crystallization, to assess crystallization temperatures and to provide information on the polymorphic content of the mixture It was established that crystallization temperatures were proportional to the volume content of the solvent in mixtures The samples were also evaluated off-line via Raman spectroscopy and SWAXS The collected data showed the presence of forms b and g in all solvent mixtures In a toluene/methanol 30:70 mixture, in addition to forms b and g, at least one of the forms A, D or a was also indicated by SWAXS The results have shown that the presence of a particular polymorph is strongly dependent on the nature and portion of the solvent in the binary solvent mixture