Design and Optimization of a Novel Strategy for the Local Treatment of Helicobacter pylori Infections.

Infections with Helicobacter pylori are a global challenge. Currently, H. pylori infections are treated systemically, but the eradication rates of the different therapy regimens are declining due to the growing number of bacterial strains resistant to major antibiotics. Here, we present a strategy for the local eradication of H. pylori by the use of Penicillin G sodium (PGS). In vitro experiments revealed that PGS shows high antibiotic activity against resistant strains of Helicobacter pylori with a minimum inhibitory concentration (MIC) of 0.125 µg/ml. In order to provide luminal concentrations above the MIC for longer periods of time, an extended release tablet was developed. Alkalizers were included to prevent acidic degradation of PGS within the tablet matrix. Out of the tested alkalizers MgO, l-Lysine, NaHCO3, and Na2CO3 NaHCO3 provided the strongest rise in pH inside the hydrated matrix when tested in simulated gastric fluid. Better PGS stability can mainly reasoned from that, addition of MgO resulted in high pH values within the matrix, causing basic degradation of PGS. This work is a first step towards the use of extended release tablets containing PGS for the local treatment of H. pylori as a safe and cost-effective alternative to common systemic treatment regimens.

Compatibility of medications with intravenous lipid emulsions: Effects of simulated Y-site mixing.

PURPOSE: To determine the physical intravenous Y-site compatibility of 19 commonly used medications at pediatric concentrations with 3 different types of lipid emulsion. METHODS: Medications at commonly used pediatric concentrations were mixed in a 1:1 ratio with lipid emulsions (Intralipid, Nutrilipid, and Smoflipid) and incubated at room temperature for 4 hours to simulate Y-site administration. Each sample was then diluted with particle-free water and analyzed using the analytical technique of light obscuration recommended in United States Pharmacopeia (USP) general information chapter 729 (USP <729>). Physical compatibility was determined by measuring the percentage of fat residing in globules larger than 5 µm (PFAT5) per USP <729> recommendations. RESULTS: Most combinations tested were physically compatible based on USP <729> regulations. Incompatibilities differed for the different brands of lipid emulsion. The two combinations that met USP <729> criteria for physical incompatibility were cisatracurium 2 mg/mL with Intralipid and gentamicin 2 mg/mL with Smoflipid. CONCLUSION: Three different lipid emulsions were physically compatible at the Y site with the majority of medications tested. Data regarding Y-site compatibility for one lipid emulsion product cannot be safely extrapolated to another without additional testing.

Y-site physical compatibility of hydrocortisone continuous infusions with admixtures used in critically ill patients.

PURPOSE: Critically ill patients with septic shock often receive multiple intravenous medications, necessitating either the placement of separate lines for medication administration or administration of medications concurrently through a Y-site connector only where compatibility has been demonstrated. The purpose of this study was to examine the physical compatibility of hydrocortisone infusions and select intravenous medications through a simulated Y site. METHODS: The medications tested for simulated Y-site physical compatibility with hydrocortisone included acetaminophen, albumin, cefepime, ciprofloxacin, cisatracurium, doripenem, epinephrine, esomeprazole, ibuprofen, levofloxacin, levothyroxine, meropenem, and norepinephrine. Hydrocortisone in solution with 0.9% sodium chloride injection was combined with an equivalent volume of solutions of each test drug at maximum or commercially available concentrations used clinically in intensive care units, as appropriate. The samples were evaluated using turbidimetric measurements and examined visually against light and dark backgrounds to determine physical compatibility. Observations and analyses were completed over a one-hour period at 15-minute intervals beginning immediately after mixing. Each test was performed in triplicate. RESULTS: All study medications demonstrated visual and/or turbidimetric physical compatibility when combined with hydrocortisone in a simulated Y-site infusion. No medications demonstrated a visual physical incompatibility when combined with hydrocortisone. CONCLUSION: Acetaminophen, albumin, cefepime, ciprofloxacin, cisatracurium, doripenem, epinephrine, esomeprazole, ibuprofen, levofloxacin, levothyroxine, meropenem, and norepinephrine exhibited physical compatibility with hydrocortisone via Y-site infusion.

Aamar-e-Advia (shelf-lives) of drugs in Unani system of medicine: A conceptual review.

In an era of globalization and increased global demand for herbal medicines, it is essential to ensure the quality and consistency of drugs. Changes in the quality of an herbal product over time should be detectable. The assessments of chemical quality and therapeutic efficacy of herbal drugs are necessary to establish their shelf-lives. Thus, stability testing is needed to establish standards for herbal products. Unani medicine has its own conceptual framework for studying health and disease. The mode of treatment includes Ilaj bit Tadbeer (regimental therapy), Ilaj bil Ghiza (dietotherapy), Ilaj bil Dawa (pharmacotherapy) and Ilaj bil Yad/Jarahat (surgery) as a final option. Ilaj bil Dawa is the most used mode of treatment. The drugs include either crude drugs prepared from plant, animal and mineral sources, called Mufrad (single) drugs or various formulations prepared from these crude drugs, called Murakkab (compound) drugs. To date, stability studies have been carried out on compound drugs, whereas only a few single drugs had had their stability tested. These studies are needed to understand how the quality of an herbal drug varies over the time when it is prepared and consumed. This may also help to standardize procedures for manufacturing compound formulations ab initio. The present study reviews the concept of Aamar-e-Advia (shelf-lives) described in the literature of the Unani system of medicine. Further, various factors that are considered important to assess the shelf-life of Unani drugs are discussed in the context of contemporary protocols for shelf-life assessment.

The right blood collection tube for therapeutic drug monitoring and toxicology screening procedures: Standard tubes, gel or mechanical separator?

Stability data of toxics or drugs in gel-based or mechanical separation blood collection tubes are lacking, especially for therapeutic drug monitoring and clinical toxicology procedures. According to ISO 15189 accreditation standard, laboratories need to master the entire preanalytical process including the stability of analytes in a specific tube. Here we explored the impact of BD PST™ II and Barricor™ separator tubes on the stability of 167 therapeutic compounds and common drugs of abuse in plasma samples using LC-MS/MS. Forty drugs were significantly affected by the use of PST™ II tubes, including antidepressants (11/26), neuroleptics (9/13), cardiovascular drugs (5/26), anxiolytics and hypnotics (4/25) and some drugs of abuse (5/26). Six compounds exhibited significant reduction by the mechanical Barricor™ tubes. Ten drugs exhibited low (<85%) but non-significant recoveries due to inter-assay variability. Besides, a logP > 3.3 was determined as a cut-off value to predict a potential lack of stability in PST™ II gel tubes with an 86.4% sensitivity and a 61.4% specificity. As a consequence, determination of drugs with a logP > 3.3 should be carried out with caution in plasma samples withdrawn on PST™ II. The study showed the Barricor™ and non-gel tubes cause less drug interference and are recommended for the drugs studied.

Emulgel based on amphotericin B and bacuri butter (Platonia insignis Mart.) for the treatment of cutaneous leishmaniasis: characterization and in vitro assays.

OBJECTIVE: This work aimed to develop and characterize a topical emulgel of amphotericin B (AmB) with bacuri butter (Platonia insignis Mart.) and evaluate its antileishmanial activity using in vitro assays. SIGNIFICANCE: Leishmaniasis is considered an infectious disease, with high incidence and capacity to produce deformities. The first-line treatment recommended by WHO, with pentavalent antimonials, is aggressive and very toxic. Therefore, the development of topical treatments can emerge as a promising and less offensive alternative. METHODS: The developed formulations were evaluated for organoleptic characteristics, centrifugation resistance, globule size, pH, electrical conductivity, viscosity, spreadability, drug content, preliminary stability, in vitro release profile, evaluation of antileishmanial activity using promastigotes forms of Leishmania major as infecting agents, macrophage cytotoxicity and selectivity index (IS). RESULTS: Formulated emulsions presented organoleptic characteristics compatible with its constituents; pH values were suitable for topical application, ranging from 4.73 to 5.02; introduced non-Newtonian shear thinning system; drug content was within the established standards, and the most suitable kinetic model of release was the first order. Regarding the in vitro assays, formulations containing both 1% and 3% of AmB presented similar outcomes, indicating a synergism between the bacuri butter and the drug, possibly showing a reduction on cytotoxicity to host cells. CONCLUSIONS: It was concluded that the formulations developed showed promising antileishmanial action and high potential for topical use.

Mixed surfactant (altering chain length and head group) aggregates as an effective carrier for tuberculosis drug.

Surface properties and aggregation behavior of cationic-cationic and cationic-non-ionic mixed surfactant systems viz. Dodecylethyldimethylammonium bromide (DDAB) with a series of double chain cationic surfactants (DiDDAB, DMDTAB, and DODAB) and non-ionic surfactants (Brij 96, Tyloxapol and Tween 80) were analysed using surface tension and transmission electron microscopy (TEM). The effect of chain length of cationic surfactant and hydrophilic-lypophilic balance (HLB) prominently observed in critical aggregation (cac) value. The aqueous solubility of anti-tuberculosis drug: rifampicin (RIF) was comparatively studied by UV-vis spectroscopy in presence of formulated micelles and vesicles. RIF was significantly solubilised in aqueous medium using all the formulated aggregates. RIF is very unstable in basic medium (above pH-7) and in oxidizing media. Therefore, stability at pH-13 as well as in strong oxidising environment was monitored using UV-vis spectroscopy. To trace the locus of the drug encapsulation in the micelles/vesicles, fluorescence spectroscopy and TEM studies were carried out. Both the techniques stemmed in complimentary results and confirmed that, RIF is majorly populated at polar medium in cationic-cationic vesicles and favour to reside at hydrophobic medium of the nonionic-cationic micelles.

Stability of compounded trilostane suspension in cod liver oil.

Trilostane is a synthetic steroid analog used to treat canine hyperadrenocorticism. For small dogs, the dose found in commercially available dosage forms of trilostane is sometimes too high. Compounding trilostane in a liquid diluent provides an option for more precise dosing and adjustments, and can be easier to administer, versus a tablet or capsule. Trilostane suspends well in cod liver oil, which is generally palatable to dogs. The stability of a compounded trilostane suspension in cod liver oil stored at room temperature was investigated for 90 days. Compounded trilostane retained stability, defined as maintaining 90-105% labeled value, for 60 days when stored in amber glass bottles. However, drug potency fell >10% below the labeled value when stored in amber plastic bottles after 7 days.

Compatibility: drugs and parenteral nutrition / Compatibilidade: medicamentos e nutrição parenteral

ABSTRACT Objective Standardization and systematization of data to provide quick access to compatibility of leading injectable drugs used in hospitals for parenteral nutrition. Methods We selected 55 injectable drugs analyzed individually with two types of parenteral nutrition: 2-in-1 and 3-in-1. The following variables were considered: active ingredient, compatibility of drugs with the parenteral nutrition with or without lipids, and maximum drug concentration after dilution for the drugs compatible with parenteral nutrition. Drugs were classified as compatible, incompatible and untested. Results After analysis, relevant information to the product’s compatibility with parental nutrition was summarized in a table. Conclusion Systematization of compatibility data provided quick and easy access, and enabled standardizing pharmacists work.

RESUMO Objetivo Padronizar e sistematizar informações, proporcionando um acesso rápido à compatibilidade dos principais medicamentos injetáveis utilizados no âmbito hospitalar para a nutrição parenteral. Métodos Foram selecionados 55 medicamentos injetáveis, os quais foram analisados individualmente com dois tipos de nutrição parenteral: dois em um, e três em um. Foram consideradas as seguintes variáveis: princípio ativo, compatibilidade dos medicamentos com a nutrição parenteral com e sem lipídios, e respectiva concentração máxima do medicamento após diluição, para os medicamentos compatíveis com a nutrição parenteral. Os fármacos foram classificados como compatível, incompatíveis e não testado. Resultados Após a análise, as informações pertinentes à compatibilidade do medicamento com a nutrição parenteral foram sintetizadas uma tabela. Conclusão A sistematização das informações de compatibilidade proporcionou um acesso rápido e fácil, viabilizando e padronizando o trabalho do farmacêutico.

Potencial hidrogeniônico de soluções de cloridrato de dobutamina expostas a condições ambientais de unidades de cuidados intensivos neonatais / Hydrogen-ion potential of dobutamine hydrochloride solutions exposed to environmental conditions of neonatal intensive care units

OBJETIVO: Verificar o potencial hidrogeniônico (pH) de soluções de cloridrato de dobutamina sob condições ambientais que mimetizam unidades de cuidados intensivos neonatais. MÉTODOS: Analisou-se pH do fármaco em solução glicosada 5 por cento ou NaCl 0,9 por cento segundo temperatura (22 e 37 °C), luz (escuro, lâmpadas fluorescentes ambiente e equipamento de fototerapia) e equipos (incolor e âmbar) em intervalos de tempo (0, 1, 24, 48, 72 e 96 horas). RESULTADOS: Evidenciaram-se valores próximos de pH do fármaco na apresentação comercial e diluído. Obteve-se média de pH de 3,45±0,19 a 22 °C e de 3,55±0,20 a 37 °C. A média de pH das soluções mantidas no escuro foi de 3,62±0,09, na luz ambiente, de 3,63±0,07, e sob fototerapia, de 3,31±0,16. Soluções em equipos incolores tiveram média menor (3,41±0,24) do que em âmbares (3,52±0,15). Obtiveram-se menores valores de pH nas soluções sob fototerapia em equipos incolores (3,17±0,03) do que em âmbares (3,55±0,03). CONCLUSÃO: Sob a luz da fototerapia houve maior variação do pH das soluções, e o emprego de equipos âmbares minimizou tal efeito.

OBJECTIVE: To verify the hydrogen-ion potential (pH) of dobutamine hydrochloride solutions under environmental conditions similar to those of neonatal intensive care units. METHODS: We analyzed the pH of the drug diluted in 5 percent dextrose in water or 0.9 percent NaCl under different conditions of temperature (22 and 37 °C) and light (dark, fluorescent light bulbs, and phototherapy equipment), using colorless and amber intravenous sets at time intervals of 0, 1, 24, 48, 72, and 96 hours. RESULTS: The pH values of the marketed form of the drug and the diluted drug were similar. The pH means were 3.45±0.19 at 22 °C and 3.55±0.20 at 37 °C. The average of the pH according to light conditions were as follows: in the dark = 3.62±0.09, under room light = 3.63±0.07, and exposed to phototherapy = 3.31±0.16. Solutions stored in colorless intravenous sets had a lower mean (3.41±0.24) than those kept in amber intravenous sets (3.52±0.15). We found lower pH values in the solutions exposed to phototherapy using colorless intravenous sets (3.17±0.03) than in those using amber intravenous sets (3.55±0.03). CONCLUSION: There was higher variation in the pH of the solutions exposed to phototherapy, and the use of amber intravenous sets reduced such effect.

Incompatibilidade entre fármacos e materiais de cateteres e acessórios da terapia intravenosa / Incompatibility among drugs and the materials of intravenous therapy catheters and disposable accessories. Descriptive study

Descriptive research whose objective was to identify the occurrence of incompatibility among drugs and the materials of intravenous therapy catheters and disposable accessories in hospitalized children, in four pediatric wards of a university hospital. The data collection was realized through the structured observation of nursing staff practice during the intravenous therapy execution. A total of 519 executions of intravenous therapy were observed in 178 children. The drugs were infused by 209 catheters, made of vialonâ, Teflonâ, stainless steel and polyurethane, being incompatibles 3.1% of the associations and in 96.9% no data was available in the literature regarding this issue. The polyvinyl chloride was the material verified in all (601) disposable accessories and 60.7% associations were compatibles, 19.8% incompatibles and for 19.5% of the associations, scientific evidences were not identified to support this nursing practice.

Pesquisa descritiva cujo objetivo foi identificar a ocorrência de incompatibilidade entre fármacos e materiais de confecção de cateteres e acessórios da terapia intravenosa administrada em crianças hospitalizadas, em quatro unidades pediátricas de um hospital universitário. A coleta dos dados foi realizada por meio de observação estruturada das execuções de terapia intravenosa desenvolvidas pelos membros da equipe. Foram identificadas 519 execuções de terapia intravenosa em 178 crianças. Os fármacos foram administrados por 209 cateteres, confeccionados em vialonâ, Teflonâ, aço inoxidável e poliuretano, sendo 3,1% das associações incompatíveis com o material e em 96,9% não se identificou referência na literatura sobre incompatibilidade. O polivinil cloreto foi material de confecção de todos (601) os acessórios utilizados para infusão de fármacos, sendo 60,7% associações compatíveis, 19,8% incompatíveis e para 19,5% observou-se a falta de evidências científicas que respaldem esta prática da enfermagem.