Resumo em Inglês:

Diacerein (DCN) was obtained by diacetylation of an anthraquinone derivative rhein and was approved by FDA in 2008, in the treatment of osteoarthritis due to its inhibitory effect on proinflammatory cytokines, including IL-6 and IL-1β. It was synthesized in 1980s and marketed as a tablet in some European Union and Asian countries from 1994. Along with its great potential in the treatment of osteoarthritis, its other applications are also being explored day by day, such as in the treatment of psoriasis, epidermolysis bullosa, breast cancer, type 2 diabetes and periodontitis. The main aim of this review is to explore mechanism of action, various applications and side effects associated with DCN. This has been reviewed that apart from the risk of diarrhea on long-term administration of DCN, various clinical studies has also shown its modest benefits in treatment of various pathological conditions. Hence, DCN is emerging as a new and potentially safe derivative with maximum therapeutic efficacies and minimum side effects which can results in improving the living status of patients suffering from various inflammatory diseases.

Resumo em Inglês:

The present study was aimed at preparation of transdermal patches of tizanidine HCl, evaluation of the effect of polymers on in vitro release pattern of the drug, and the effect of permeation enhancers on the penetration of the drug through the rabbit skin. Various proportions of hydrophilic (HPMC) and hydrophobic (Eudragit L-100) polymers were used with PEG 400 as film-forming agent, and Span 20 or DMSO as permeation enhancer. The formulations were assessed for physicochemical characteristics and in vitro drug release studies using USP paddle over disc method in phosphate buffered saline (pH 7.4) at 32.0±1°C. On the basis of in vitro studies and physicochemical evaluations, S03-A and S04-A were selected at Eudragit : HPMC ratios of 8 : 2 and 7 : 3, respectively, for further ex vivo analysis. The effects of different concentrations of Span 20 and DMSO were evaluated on excised rabbit skin using Franz diffusion cell. Cumulative drug permeation, flux, permeability coefficient, target flux, and enhancement ratio were calculated and compared with the control formulations. Kinetic models and Tukey’s multiple comparison test were applied to evaluate the drug release patterns. Formulation SB03-PE containing Eudragit L-100:HPMC (7:3) with Span 20 (15% w/w) produced the highest enhancement in drug permeation, and followed zero order kinetic model with super case-II drug release mechanism.

Resumo em Inglês:

Although dispensing of medication has been addressed by theoretical models, studies that confirm the impact of this service are still needed. The objective was to evaluate the impact of a new model of medicine dispensing system on patients’ medication knowledge, adherence to treatment and satisfaction. One hundred and four patients attending the dispensing service of a community pharmacy between 21 January 2013 and 20 April 2013 were included in this intervention study. The impact of the service on patients’ medication knowledge, adherence to treatment and satisfaction was assessed by using validated questionnaires at two time points: at the moment of medication dispensing and 30 days thereafter by telephone contact. Statistical analysis was performed by McNemar’s test, and a p<0.05 was set as statistically significant. The number of patients showing insufficient knowledge about medications decreased by 50% (p < 0.05), and the number of those showing sufficient knowledge was three times greater (p < 0.05) after medicine dispensing. A high level of satisfaction was observed. Improvement of medication adherence, however, was not observed. The proposed system model for drug dispensing improved patients’ knowledge about medication and satisfaction.

Resumo em Inglês:

Pyrimidine derivative 3 was afforded through the reaction of compound (1) with 5-ureidohydantion (2). Product 3 underwent a cyclization to produce fused pyrimidine derivative 7, although the latter product 7 was synthesized through one step via the reaction of compound (1) with 5-ureidohydantion (2) using another catalyst. Compound 3 was oriented to react with cyclic ketones 8a,b in the presence of elemental sulfur, salicylaldehyde (10), aryldiazonium chlorides 12a,b and ω-bromo-4-methoxy- acetophenone (14), which afforded, fused thiophene derivatives 9a,b, coumarin derivative 11, arylhdrazono derivatives 13a,b and 4-methoxyphenyl butenyl derivative 15, respectively. The latter product 15 was reacted with either potassium cyanide (16a) or potassium thiocyanide (16b) to form cyano and thiocyano derivatives 17a,b, respectively. Compound 17a underwent further cyclization to afford pyridopyrimidine derivative 19. Compound 15 was reacted with either hydrazine (20a) or phenylhydrazine (20b) to produce hydrazo derivatives 21a,b and these products were cyclize to produce pyrrole derivatives 23a,b. Finally, 5-ureidohydantion (2) was reacted with compounds 24a,b,c to afford pyrimidine derivatives 25a,b,c. The structures of the synthesized compounds were confirmed using IR, 1H NMR, 13C NMR and mass spectrometry techniques. Compounds 11 and 19 have promising as analgesic and antipyretic activities.

Resumo em Inglês:

Dextromethorphan hydrobromide (DM) sustained release matrix pellets containing 10% w/w drug were prepared by an extrusion/spheronization technique. The effect of mixing different concentrations of ethyl cellulose (EC), hydroxypropyl methylcellulpse (HPMC K10), and Carbopol 934 with Avicel PH101 on the rheological properties of pellet wet mass was evaluated using mixer torque rheometry (MTR). The prepared pellets were characterized for size, drug content, and in-vitro DM release rate. The results showed that increasing the concentration of the hydrophobic polymer (EC) with Avicel PH101 decreased wet mass consistency, represented by mass mean line torque. Lower binder ratio was required for optimum wet massing, while mixing with swellable polymers (HPMC and Carbopol) caused a noticeable increase in both mean line torque and binder ratio. Combinations of HPMC and Carbopol at higher concentrations resulted in controlled in vitro release of DM from the prepared pellets. Furthermore, mathematical treatment of the in vitro release data of DM from the prepared pellets showed that all formulations except those containing 5% Carbopol plus 5% HPMC (F10) follow first order release. n values of these formulation were in the range of 0.09-0.40, which support an anomalous non-Fickian release.

Resumo em Inglês:

Flurbiprofen belongs to Biopharmaceutical Classification System (BCS) class II drugs which are poorly soluble in water. The objective of present research work was to prepare fast dissolving tablets of Flurbiprofen using varying concentrations of three different sublimating agents to improve the dissolution rate. Seven formulations were prepared containing different concentrations of camphor, ammonium bicarbonate and thymol as sublimating agent along with primogel as a superdisintegrant. Tablets were manufactured by direct compression method. The prepared tablets were evaluated for pre-compression and post-compression parameters result, For all formulations result was within official limits. FTIR studies revealed that there were no interactions between the drug and the excipients used. From in vitro drug release studies it was concluded that the formulations F6 and F7 containing 10% and 15% of thymol showed fast drug release of 100.00% and 100.84% respectively in 30 minutes. Formulations containing camphor (F2 & F3) and ammonium bicarbonate (F4 & F5) as sublimating agents showed a drug release of less than 80%, while the control formulation F1 having no sublimating agent showed 49.14% of drug release in 30 minutes. Thus thymol can successfully be used to formulate fast dissolving tablets of flurbiprofen by sublimation method with much better dissolution profile.

Resumo em Inglês:

Generally, Plants have immense potential in the wounds management and treatment.In Chinese herbology, Hibiscus plant is a potent herb and have a good medicinal values but not scientifically approached. The present study aims to investigate the wound healing and antimicrobial activity of ethanolic extract of Hibiscus hirtus Linn.(HH). Wound healing activity was carried out by excision, incision and burn wound models. Antimicrobial activity was determined by cup plate method. Healing rate was assessed from the rate of wound contraction, epithelialization rate, tensile strength, hexosamine and hydroxyproline content. From the obtained results, it was indicated that the wound contraction and increased tensile strength of Hibiscus hirtus extract exhibits potent wound healing capacity. Hexosamine and hydroxyproline expression were also correlative with the pattern of healing observed. Histological observation indicates that the wounds treated with Hibiscus hirtus extract and povidone iodine have reduced scar formation and enhances fibroblast proliferation, angiogenesis, keratinization and epithelialization. The Hibiscus hirtus extract has excellent antimicrobial activity against the various organisms. Wound healing activity of our ethanolic extract of Hibiscus hirtus has shown the good effect which has proved by different physical, histological, biochemical parameters. Significant antimicrobial activity shown may be due to major active constituents present in plant.

Resumo em Inglês:

Multiparticulate systems have biopharmaceutical advantages when compared to the monolithic systems, once they allow different patterns of drug release and can be used in different treatments. The aim of the present work was to develop a biphasic controlled release delivery system, using propranolol hydrochloride (PROP) that can be used for the treatment of circadian diseases. This system was obtained by the combination of cellulosic polymers hydroxypropyl methylcellulose (HPMC) and ethylcellulose (EC) in a 2² factorial experimental design, which allowed the optimization of the development stage. The pellets produced and used in biphasic formulations were evaluated for physical and chemical characteristics and presented acceptable results. The immediate fraction obtained showed the complete release in 30 min while the others kept the release of the drug for 24 h. This study showed that the combination of beads with different releasing characteristics allowed to obtain different release profiles, which can be modulated according to the pathological needs, especially with regard to circadian diseases that suffer alterations throughout the day.

Resumo em Inglês:

Colonic carcinoma is one of the most common internal malignancies and is the second leading cause of deaths in United States. Methotrexate (MTX) is a drug of choice in the treatment of colon cancer. The aim of the present research work was to develop and characterize colon targeted pellets of MTX for treatment of colonic carcinoma. The product and process parameters were optimized by screening methods. Pellets were prepared by extrusion spheronization using microcrystalline cellulose (MCC) as spheronizing aid and ethyl cellulose (EC) as release retardant in different ratio. Based on the physical appearance, sphericity and % in vitro drug release, batch P17 containing EC: MCC (3:7) was optimized for core pellets. The site specificity was obtained by screening the coating polymers and by coating the core pellets with EudragitS100. The 32 full factorial design was applied in which airflow rate (X1) and coating time (X2) were the independent parameters and physical appearance (Y1) and time taken for 100% drug release (Y2) were selected as the dependent variables. From the results obtained, 6min of coating time and 60cm3/min airflow rate was optimized. The batch B5 showed appropriate physical appearance and % in vitro drug release upto 17hr indicating sustained release property. The ex-vivo studies performed on rat colon indicated a significant relation with the in vitro drug release. The drug release followed Higuchi’s model indicating the diffusion pattern of drug release from the matrix of pellets. Thus, the coated pellets can be a good candidate for site specific delivery of MTX to colon by decreasing the gastric irritation and thus to improve bioavailability.

Resumo em Inglês:

In the current work, a sustained drug delivery system of flutamide (FLT) was developed using Poly(D,L-lactide-co-glycolide) (PLGA) decorated bypoly(ethylene glycol) (PEG) grafted prazosin (PLGA-PEG-Praz) as a targeting moiety. In a multi-step reaction, PLGA was linked to PEG and prazosin. The structure of the synthesized polymers was confirmed by FTIR and 1H-NMR. Flutamide-loaded nanoparticles were prepared by quasi-emulsion solvent diffusion technique. The nanoparticles were evaluated for size, zeta potential, polydispersity index, drug crystallinity, loading efficiency, and release properties. Also, the physicochemical properties of the nanoparticles were analyzed using Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry, and Powder X-Ray Diffractometry (XRD). The particle size of nanoparticles was ranged between 191 and 249 nm. Loading efficiency of nanoparticles was about 43%-69%. Results showed a steady release rate for nanoparticles compared to that of a pure drug powder. SEM characterization confirmed that particles were in nanosize range. DSC and XRPD results verified a decrease in drug crystallinity in the prepared formulations. In conclusion, the results of this study showed that PLGA-PEG-Praz nanoparticles could be a good choice to improve the physicochemical properties of the drug and these formulations can increase Flutamide efficacy.

Resumo em Inglês:

A liquid chromatography method was developed and validated for the determination of gemifloxacin in human plasma using chloramphenicol as internal standard to achieve lower quantification limit. Acetonitrile was used to precipitated and extracted analyte and internal standard from plasma by Protein Precipitation. Analysis was performed isocratically on C18 column using 25% acetonitrile and 75% 0.02 M phosphate buffer as mobile phase. The method was demonstrated to be linear from 0.003 µg/mL to 5 µg/mL with the lower limit of quantitation of 0.003 µg/mL. The method was successfully applied for the bioequivalence study of gemifloxacin after a single oral administration of 320 mg gemifloxacin mesylate tablets to 12 healthy volunteers.

Resumo em Inglês:

The novel alkaloid, oleracimine, presented remarkable anti-inflammatory bioactivity, and therefore, its pharmacokinetics was investigated in rat plasma after intravenous and oral administration by using a rapid ultra-high-performance liquid chromatography (UHPLC) method with UV detection at 270 nm. The analysis was performed on a shim-pack ODS column (75 mm×2 mm, 1.6 µm particle size, Shimadzu, Japan) column using isocratic elution with a mobile phase consisting of methanol-water (62:38, v/v) within 3 min. The results indicated that oleracimine was rapidly distributed with Tmax for 11.7 min after oral administration, which presented the double-peak phenomenon in the pharmacokinetic profile with a higher oral absolute bioavailability of 55.1% ± 7.83%.

Resumo em Inglês:

A new group of hybrid nitric oxide-releasing anti-inflammatory drugs (NONO-coxibs), in which an O 2-acetoxymethyl-1-(N-ethyl-N-methylamino)diazen-1-ium-1,2-diolate NO-donor moiety is attached directly to the carboxylic acid group of 1-(4-aminosulfonylphenyl)-5-aryl-1H-pyrazol-3-carboxylic acids (6a-c), were synthesized. A low amount of NO was released from the diazen-1-ium-1,2-diolate compounds 6a-c upon incubation with phosphate buffer saline (PBS) at pH 7.4 (range: pH 7.97-8.51), whereas, the percentage of NO released was significantly higher (84.5%-85.05% of the theoretical maximal release of two molecules of NO/molecule of the parent hybrid ester prodrug) when the diazen-1-ium-1,2-diolate ester prodrugs were incubated in the presence of rat serum. These incubation studies demonstrated that both NO and the anti-inflammatory 1-(4-aminosulfonylphenyl)-5-(4-H, 4-F or 4-Me-phenyl)-1H-pyrazol-3-carboxylic acid (4a-c) would be released from the parent NONO-coxib upon in vivo cleavage by non-specific serum esterases. The parent compounds 4a-c displayed good anti-inflammatory effects (ID50=81.4-112.4 mg/kg p.o.) between those exhibited by the reference drugs, aspirin (ID50=114.3 mg/kg p.o.) and celecoxib (ID50=12.6 mg/kg p.o.). Hybrid ester anti-inflammatory/NO-donor prodrugs (NONO-coxibs) offer a potential drug-design concept directed toward the development of anti-inflammatory drugs that are lacking adverse ulcerogenic and/or cardiovascular effects.

Resumo em Inglês:

The aim of this study was to develop and evaluate a corrective and photoprotective makeup for patients with dyschromias. An emulsion was prepared and pigment mixtures were incorporated in the formulation, producing five shades of corrective makeup: BEIGE (I, II, III), BRONZE and TAN. The sun protection factor (SPF) and UVA/UVB ratio of the corrective makeup were determined using spectrophotometry with a Labsphere® analyser. The spreadability, occlusivity, stability, and photostability of the photoprotective formulations were also evaluated. For all formulations there was no statistical difference among them (p > 0.05) in terms of spreadability, occlusivity and SPF. They were considered to be photostable under solar radiation, with variations in SPF value and UVA/UVB ratio lower than 20%. The corrective makeup presented average-to-high UVB photoprotection and broad spectrum photoprotection. After 90 days, pH, density and SPF values showed no significant differences among formulations (p>0.05). All corrective makeup presented separation of the pigments, however, they returned to a homogeneous aspect and to the original color shade after shaking. The corrective makeup presented a fine texture, little brightness, and a homogeneous, dry-to-the-touch aspect. This work may benefit patients with dyschromias, improving their quality of life, besides promoting photoprotection and covering the skin blemishes.

Resumo em Inglês:

This study aims to assess the perceived practice and barriers towards the provision of asthma management services among urban community pharmacists in Selangor, Malaysia. The study also highlights both pharmacist and patient-related barriers in asthma counseling. One hundred fifty urban community pharmacists in Selangor, Malaysia, were randomly selected and recruited for the present cross sectional baseline study. Previous studies have explored pharmacists’ perception on their roles in asthma management in different parts of the world. The data was collected through self-explanatory questionnaires (containing 47 items). The extracted data from the completed questionnaires were analyzed descriptively and inferentially using Statistical Package for Social Science (SPSS) version 19. Results showed that pharmacists perceived their roles in asthma management along three major dimensions: ‘patient self-management’, ‘medication use’ and ‘asthma control’, mean (±SD) score of the perception towards asthma management was 99.29 ± 4.58 over a maximum possible score of 110 with 90.26%. There were significant differences between the pharmacy education level and perceived practice of asthma management while there were insignificant differences between age, gender, ethnicity, number of practicing year and perceived practice of asthma management among respondents. Most common barriers towards asthma counselling including lack of time, lack of asthma knowledge, lack of counselling space and cost of asthma drugs. Conclusively, urban community pharmacists in Selangor, Malaysia, demonstrate good perceived practice of better management of asthma with multidimensional dimensional role against in disease care.

Resumo em Inglês:

Psoriasis is a T-cell mediated disease that involves IL-23/Th17 and IL-12/Th1 axes. Ustekinumab, a fully human monoclonal antibody targeting the p40 subunit of both IL-12 and IL-23, has proven to be efficient and safe for treating patients with psoriasis. Yet, there have been no reports with human skin/blood samples that would elucidate the molecular mechanisms by which ustekinumab calms psoriasis skin lesions. To investigate the efficacy and molecular pathway (RORC, t-BOX and GATA) of ustekinumab in treating patients with psoriasis skin lesions. A total of 30 patients with psoriasis were randomized into placebo group and treatment group. PASI of each patient was calculated at 0, 12 and 24 weeks post-treatment. The mRNA levels of RORC, t-BOX and GATA in peripheral blood mononuclear cells separated from patients’ whole blood were analyzed using qPCR. Decreased mRNA of RORC, t-BOX and GATA were observed after continuous injections, indicating that ustekinumab exerts its effect by interacting with these molecules; while no significant difference in foxp3 mRNA levels were found between placebo group and treatment group.

Resumo em Inglês:

All-trans retinoic acid (ATRA) has been studied for the treatment of cancer, including leukemia and breast cancer. This work aims to develop nanoemulsions (NE) loaded with a hydrophobic ion pair (HIP) of all-trans retinoic acid (ATRA) and a lipophilic amine, stearylamine (SA), and coated with hyaluronic acid (HA) to enhance anticancer activity and reducing toxicity. Blank NE was prepared by spontaneous emulsification and optimized prior to HIP incorporation. NE-ATRA was electrostatically coated with different concentrations of HA. Incorporation of ATRA-SA led to monodisperse NE with small size (129 ± 2 nm; IP 0.18 ± 0.005) and positive zeta potential (35.7 ± 1.0 mV). After coating with 0.5 mg/mL HA solution, the mean diameter slightly increased to 158 ± 5 nm and zeta potential became negative (-19.7 ± 1.2 mV). As expected, high encapsulation efficiency (near 100%) was obtained, confirmed by polarized light microscopy and infrared analysis. Formulations remained stable over 60 days and release of ATRA from NE was delayed after the hydrophilic HA-coating. HA-coated NE-ATRA was more cytotoxic than free ATRA for MDA-MB-231 and MCF-7 breast cancer cell lines, especially in the CD44 overexpressing cells. Blank coated formulations showed no cytotoxicity. These findings suggest that this easily-made HA-coated NE-ATRA formulation is a promising alternative for parenteral administration, thus improving the breast cancer therapy with this drug.

Resumo em Inglês:

The aim of this study was to evaluate interruption of treatment with biological drugs and tofacitinib due to adverse events in patients with rheumatoid arthritis. A systematic review was performed in the electronic databases MEDLINE, Cochrane, Scopus, CRD, IPA, Lilacs and Scielo. Case reports addressing interruption of treatment due to any adverse event related to abatacept (ABA), adalimumab (ADA), anakinra (ANA), certolizumab pegol (CER), etanercept (ETA), golimumab (GOL), infliximab (IFX), rituximab (RTX), secukinumab (SEC), tocilizumab (TCZ), tofacitinib (TOF) or ustekinumab (UST) in rheumatoid arthritis patients were evaluated. Baseline data, patient profile, previous and current treatments, cause of discontinuation and information on reintroduction of treatment were extracted from the case reports. One hundred and fifty-four studies (154 patients) reported 162 discontinuations of rheumatoid arthritis treatment due to adverse events (ETA = 57; IFX = 46; ADA = 32; TCZ = 13; RTX = 5; ANA = 3; GOL = 2; ABA = 2; TOF = 1; CER = 1; SEC = 0 and UST = 0). The mean age of patients was 56 (± 12.1) years and 82% were female. Seventy-four adverse events were confirmed (related to used drug), and 138 were observed in patients using anti-TNF. The most common adverse events were infections (21%), skin disease (15%), autoimmune disease (13%) and hematological disorders (9%). Case reports are important in the detection of rare adverse events and should be considered in the choice of appropriate therapy for patients.

Resumo em Inglês:

The aim of the present study is to illustrate the effects of swertiamarin (STM), a natural iridoid from herbal medicines, on hepatic inflammation induced by carbon tetrachloride (CCl4) in rats. Male Sprague Dawley rats were exposed to CCl4 with or without STM co-administration for 8 weeks. Our results revealed that STM administration (100 and 200 mg/kg b.w.) significantly attenuated inflammation in livers of CCl4-treated rats. STM remarkably reduced the production of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein-1a (MIP-1α), and monocyte chemotactic protein-1 (MCP-1) in liver tissue of CCl4-treated rats. In addition, STM treatment downregulated connective tissue growth factor (CTGF) and ser307pIRS-1 expression, which was induced by CCl4 exposure. In the process of exploring the anti-inflammatory mechanisms of STM action, we demonstrated that STM significantly inhibited Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) p65 expression in the liver. In conclusion, these results suggested that the inhibition of CCl4-induced inflammation by STM was, at least in part, due to its regulation of the TLR4 /NF-κB signaling pathway.

Resumo em Inglês:

Present work is aimed to develop a simple, sensitive, robust and reliable HPLC method for routine quality control of epirubicin (EPI) in bulk drug, marketed injections and polymeric nanoparticles. Separation was carried out by C18 column. Isocratic elution was carried out using mobile phase A: 0.16% o-phosphoric acid solution, B: acetonitrile and methanol mixture (80:20, v/v) in the ratio of 60:40 (A: B) while the flow rate was maintained at 1mL/min. Analyses were performed at 233.5 nm using PDA detector. Excellent linear relationship was observed between peak-area versus drug concentration in the range of 1.0-100.0 μg/mL (r2, 0.999). Developed method was found to be sensitive (Limits of detection and quantification were found to be ~8 ng/mL and ~25 ng/mL, respectively), precise (RSD <1.0%, for repeatability and <2.0% for intermediate precision, within acceptable ranges of precision), accurate (recovery in different dosage form, 94.65 -100.26%, within acceptable range, 80-120%), specific and robust (% RSD <2, for system suitability parameters). Stress-induced degradation studies demonstrated that method can suitability be applied in the presence of degradants. Developed method has been successfully applied for the determination of entrapment efficiency, drug loading, in vitro release profile, in vitro permeation studies as well as stability assessment of polymeric nanoparticles.

Resumo em Inglês:

The discovery and development of novel inhibitors with activity against variants of human immunodeficiency virus type 1 (HIV-1) is pivotal for overcoming treatment failure. As our ongoing work on research of anti-HIV-1 inhibitors, 32 N-arylsulfonyl-3-acylindole benzoyl hydrazone derivatives were prepared by introduction of the hydrazone fragments on the N-arylsulfonyl-3-acylindolyl skeleton and preliminarily screened in vitro as HIV-1 inhibitors for the first time. Among of all the reported analogues, eight compounds exhibited significant anti-HIV-1 activity, especially N-(3-nitro)phenylsulfonyl-3-acetylindole benzoyl hydrazone (18) and N-(3-nitro)phenylsulfonyl-3-acetyl-6-methylindole benzoyl hydrazone (23) displayed the most potent anti-HIV-1 activity with EC50 values of 0.26 and 0.31 μg/mL, and TI values of >769.23 and >645.16, respectively. It is noteworthy that introduction of R3 as the methyl group and R2 as the hydrogen group could result in more potent compounds. This suggested that introduction of R3 as the methyl group could be taken into account for further preparation of these kinds of compounds as anti-HIV-1 agents.

Resumo em Inglês:

A simple and fast alternative methodology using capillary zone electrophoresis (CZE) to analyze linezolid and its cationic photodegradation products in tablets has been developed. The separation was carried out on fused silica capillary and conducted using 100 mM formic acid (pH 3.0) and by applying 30 KV voltage. Detection was performed at UV 254 nm. The optimized method was validated in terms of linearity, limits of detection and quantification, precision (repeatability), stability studies (selectivity) and accuracy. Good linearity (8-20 mg L-1) was obtained and the limit of detection was 0.95 mg L-1. The greatest advantages of the CZE method were the rapid set-up of instrumentation and capillary equilibration, short analysis time (12 min), low running cost and low waste generation. The method showed good stability in determining linezolid submitted to degradation by light and to a climatic chamber and can be used as an alternative for evaluation in stability studies of linezolid in tablets, as well as for the analysis of the drug in raw materials and finished products.

Resumo em Inglês:

The main objective of the present work was to enhance the solubility and dissolution rate of poorly water-soluble drug cefuroxime axetil (CA) by formulating it into solid dispersions (SDs) with water soluble carrier poloxamer 188. Different methods were employed to prepare the dispersion, such as: Solvent method (SM), Kneading method (KM), Melt evaporation method (MEM) and Physical mixture (PM) in different drug: carrier ratios 1:1, 1:2 and 1:3 (cefuroxime axetil: poloxamer 188). The physical mixture(s) and solid dispersion(s) were characterized for drug carrier interaction, drug content, solubility, dissolution rate, differential scanning calorimetry (DSC) and FT-IR study. The dissolution rate of the prepared solid dispersion systems was determined in phosphate buffer (pH 6.8) for 1 h. The solubility of drug from different systems was also determined in water. All SD formulations were found to have a higher dissolution rate comparatively to pure CA. The dissolution rate was enhanced in the following order SM > MEM > KM. The enhancement of dissolution rate may be caused by increase wettability, dispersibillity reduction in particle size or the formation of CA β crystalline. The FT-IR study probability revealed that there was no chemical interaction between drug and poloxamer 188.

Resumo em Inglês:

The stability of vitamins A, E, and C was determined in 12 brands of vitamin supplements over a 12-month storage period. The variations in concentrations of these vitamins across three different batches of five brands were measured. Vitamins A and E was determined by HPLC method, and vitamin C was measured by using potentiometric titration. All samples for stability studies were maintained at room temperature and protected from light. Measurements were carried out in the first semester of the expiration date and then every six months up to 12 months of storage. After this period, only one sample showed no significant decrease in vitamin A and E concentrations in relation to the concentrations measured at the beginning of the study. The concentration of vitamin C showed no significant decrease in 50% of the samples after 6 months of storage, although after 12 months, 92% had significant losses in concentration. The analysis of the different batches showed significant variations in the vitamin levels, which do not seem to be significant for inspection purposes considering the tolerance outlined in the legislation. Over-fortification of vitamin supplements during manufacture seems to be required, but the additional amount of supplementation will depend on each sample.

Resumo em Inglês:

The purpose of this study was to evaluate the safety of Kalanchoe brasiliensis extract, followed by the development of an oil in water emulsion containing the K. brasiliensis leaves extract and evaluating its clinical moisturizing efficacy. The formulations containing sodium acrylates/ Beheneth-25 methacrylate Crosspolymer (and) hydrogenated polydecene (and) lauryl glucoside and 0.5% of extract were prepared. The extract was considered as non-irritating through skin irritant tests. The stability testing was carried out in different conditions for 90 days. The skin hydration was measured by capacitance measurement and transepidermal water loss using biophysical techniques. The results indicate that the formulation containing 0.5% of extract increased the hydration of the stratum corneum up to 5 h after application on the forearm. The transepidermal water loss was reduced when compared to the untreated area and placebo area. Therefore, we can conclude that the increased skin hydration and protection of barrier function can be attributed to the K. brasiliensis extract. This research presents a new raw material from the Brazilian Caatinga biome and shows its possible application in the development of cosmetic products.

Resumo em Inglês:

As there are a lot of antibacterial and anti-fungal resistant pathogens, researchers attempt to substitute antimicrobial drugs with various medical plants and novel nanoparticles. The present study was conducted to characterize antimicrobial activities of Euphorbia prostrata and Pelargonium graveolens extract alone and in combination with Mn-Ni@Fe3O4-NPs & Mn: Fe (OH)3-NPs on the DNA cleavage of E. coli and also Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Aspergillus oryzae, and Candida albicans. The effects of antimicrobial activities on above scenarios were evaluated using disc diffusion, MIC, MBC, and E. coli DNA electrophoresis methods. The results showed that the effects of antibacterial assay values of Euphorbia prostrata & Mn: Fe(OH)3 was 21.00 mm for E. coli and while it was 19.5 mm for Euphorbia prostrata & Mn-Ni@Fe3O4 against Pseudomonas aeruginosa at a concentration of 100mg/mL. The highest level of DNA cleavage was seen in mixed of Euphorbia prostrata & Mn: Fe(OH)3 nanoparticles. In conclusion, the combination of Euphorbia prostrata and Pelargonium graveolens extracts with nanostructures showed synergic effects on eliminating the bacteria via DNA destruction and others mechanisms. Moreover, the synergistic effect of nanoparticles with plant extracts seems to bring about new choices for the treatment of infectious diseases.

Resumo em Inglês:

Oviductus ranae (OR) is a traditional Chinese medicine, which was first recorded in the Compendium of Materia Medica in the Ming Dynasty. OR contains high amounts of proteins and elicits therapeutic effects on neurasthenia, insomnia, and respiratory symptoms, which are related to oxidative stress and immunodeficiency. This study aimed to obtain the potential of OR for the development of functional food possessing antioxidant and immune-enhancement functions in the same dose. In antioxidant evaluation, OR can significantly decrease malondialdehyde and protein carbonyls (P < 0.05, P < 0.01) and significantly increase total superoxide dismutase and glutathione in a dose-dependent manner (P< 0.05, P < 0.01) against ethanol-induced oxidative stress in mice at 0.1, 1.0, and 3.0 g/kg BW. In immunomodulatory evaluation, OR could significantly enhance the phagocytosis of liver macrophages (P < 0.05, P < 0.01), delayed-type hypersensitivity response (P < 0.05, P < 0.01), hemolytic activity (P < 0.05), antibody-producing cells (P < 0.05), and natural killer cell activity (P < 0.05) in the same dose range described in antioxidant evaluation compared with those in the normal control. OR slightly influenced lymphocyte proliferation, peritoneal macrophage phagocytosis, and immune organ indices in mice. Thus, 3.0 g/kg BW OR showed potential for the development of functional food with antioxidant and immune-enhancement activities.

Resumo em Inglês:

The present study aimed to evaluate the effect of the adjuvant use of resveratrol with meloxicam on the clinical scores of knee OA patients. This was a double-blind placebo-controlled randomised trial involving 100 patients with knee osteoarthritis performed at the Shar Teaching Hospital, Sulaimani General Hospital and Specialised Rheumatology Center, Sulaimani City from December 2016 to September 2017. The efficacy of the treatment was evaluated by measuring the changes from baseline in the KOOS score, WOMAC index, and VAS-100 score after 90 days of treatment. Resveratrol significantly improves the knee OA pain and associated symptoms compared with placebo, and both clinical scores were found to be eligible for following treatment outcomes. In conclusion, resveratrol, when used in combination with meloxicam, improves pain and symptom scores in patients with mild-to-moderate knee OA compared with placebo. The intervention with a dietary supplement may significantly impact the pain and overall quality of life in patients with knee OA.

Resumo em Inglês:

Seaweeds constitutes an abundant marine reserve that can be harnessed as source of new pharmaceutical agents. Sargassum binderi Sonder ex J. Agardh is a brown seaweed that is predominantly available from December to March in the Red Sea, Jazan, Kingdom of Saudi Arabia (KSA). In this study, three extracts were isolated using three different techniques, and were subjected to antibacterial assay. The petroleum ether extract of Sargassum binderi was more effective against selected human pathogenic bacteria than the other extracts. Therefore, further studies were focused on developing oleic acid vesicles entrapped with the petroleum ether extract of Sargassum binderi, with the aim of enhancing its penetration property. Oleic acid vesicles were prepared by entrapping petroleum ether extract of Sargassum binderi using film hydration technique. The formulated vesicles were in nanoscale, and so were termed phyto-nanovesicles (PNVs). The spectrum of antibacterial activity of PNVs showed that it is a promising formulation against S. aureus, S. pyogenes, B. subtilis, E. coli, K. pneumoniae and P. aeruginosa. The microbial sensitivities to the PNVs was in the order E.coli > B. subtilis > S. aureus > S. pyogenes > K. pneumoniae > P. aeruginosa. Thus, the PNV formulation possesses promising and effective antimicrobial potential against human pathogenic bacteria.

Resumo em Inglês:

Risperidone is an atypical antipsychotic acting mainly as a dopamine D2 and serotonin 5-HT2 receptors antagonist prescribed in the treatment of schizophrenia and various affective disorders. Risperidone has been reported to be associated with weight gain, panreatitis and type 2 diabetes mellitus. Various mechanisms of risperidone-induced toxicities have been reported but the histology of tissues especially pancreas has never been studied. Therefore, the current study was designed to elucidate the toxic effects of chronic administration of risperidone on pancreas, liver and kidneys. Animals (rats) of either gender were divided into two groups, the risperidone and control groups. Risperidone was administered in a dose of 2.5 mg/kg/d for three weeks. The controls received acidified saline only. Both the groups received restricted diet (20 g/12 h). The body weight and level of random blood sugar (RBS) were measured on a weekly basis. The levels of lipase and amylase were determined at the conclusion of the experiment. At the end of the experiment, the tissues were dissected out for histopathological evaluation. Risperidone showed no weight gain, hyperglycemia or rise in the level of lipase (P> 0.05); however, the level of amylase was raised (***P<0.05). Histological examination under light microscope showed no hepatotoxicity, nephrotoxicity but did show damage to the pancreas. The findings of this study indicated that the incidence of adverse effects associated with risperidone could be prevented/alleviated/delayed by allowing restricted diet.

Resumo em Inglês:

From drug repurposing studies, this work aimed to evaluate the activity of different pyrazinoic acid (POA) derivatives against Sporothrix brasiliensis. The POA esters were prepared and characterized as previously reported by classical esterification reactions, with good to excellent yields. Sporothrix brasiliensis isolates from cats (n=6) and standard strains of S. brasiliensis and S. schenckii were used to assess the antifungal activity of the POA derivatives through broth microdilution assay (CLSI M38-A2). Among the tested compounds, molecules 3 and 4 showed fungistatic and fungicidal activities against all Sporothrix spp. strains, and the obtained MIC and MFC values ranged from 2.12 to 4.24 mg/mL and from 1.29 to 5.15 mg/mL, respectively. Compound 2 and 5 were active as in vitro inhibitors of fungal growth, but showed weak fungicidal activity, while molecules 1 and POA itself were inactive. The results suggest the activity of POA derivatives against Sporothrix spp. may be dependent on the lipophilicity. In addition, the antifungal susceptibility of the isolates to itraconazole was performed, showing that two Sporothrix isolates from cats were itraconazole-resistant. Compounds 3 and 4 were also active against these itraconazole-resistant isolates, indicating a possible alternative route to the standard mode of action of itraconazole.

Resumo em Inglês:

The objective of the study was to evaluate the use of human albumin in a Brazilian university hospital, in compliance with the institutional protocol and other clinical guidelines, taking into account the therapeutic indications and the dosage regimens. Data was obtained from the pharmacy dispensing records of human albumin, the requests for use it and, when available, the patient’s records between January and October 2017. After evaluation the therapeutic indications and the dosage regimens were classified as “appropriate” and “inappropriate”. The analysis of 98 requests showed that, when compared to the institutional protocol, 54 (55.1%) requests had an inappropriate therapeutic indication. However, when a comparison was made between 25 medical records (54 requests) and other clinical guidelines, it was observed that the therapeutic indication had none classified as inappropriate. In addition, 16 (29.7%) requests were considered inappropriate in relation to dosage regimens. From these results, it was possible to conclude that although the use of human albumin in the hospital was associated to a clinical protocol, it was outdated. Thus, it is possible to affirm that not only the adoption of a clinical protocol, but its periodical updating is an important strategy to promote the rational use of drugs.