RESUMEN
The division of tablets and adequate methods of splitting them are a complex problem in all sectors of health care. Although tablet-splitting is often required, this procedure can be difficult for patients. Four tablets were investigated with different external features (shape, score-line, film-coat and size). The influencing effect of these features and the splitting methods was investigated according to the precision and "weight loss" of splitting techniques. All four types of tablets were halved by four methods: by hand, with a kitchen knife, with an original manufactured splitting device and with a modified tablet splitter based on a self-developed mechanical model. The mechanical parameters (harness and friability) of the products were measured during the study. The "weight loss" and precision of splitting methods were determined and compared by statistical analysis. On the basis of the results, the external features (geometry), the mechanical parameters of tablets and the mechanical structure of splitting devices can influence the "weight loss" and precision of tablet-splitting. Accordingly, a new decision-making scheme was developed for the selection of splitting methods. In addition, the skills of patients and the specialties of therapy should be considered so that pharmaceutical counselling can be more effective regarding tablet-splitting.
Asunto(s)
Composición de Medicamentos/métodos , Comprimidos , Bisoprolol , DipironaRESUMEN
Hydrogen-bonded interpolymer complexes are prepared using special polymers interactions between relatively weak hydrogen bonds and other components when they are numerous with consecutive configurations. Drug molecules possessing hydrogen donor or acceptor groups or both intercalate into the complex and show different release patterns. While numerous studies have investigated polymer component behaviours in different media and the resulting drug release profiles, few have focused on the specific drug molecule state. Desloratadine was incorporated into a Carbopol(®)-polyvinylpyrrolidone (PVP) complex using a novel method and the dissolution and release profiles as well as the mediating interactions were investigated at different pH values. Our results indicate that the drug showed an immediate release pattern at an acidic pH, and therefore, the polymer complex likely had no dissolution retarding effect on the developed system. Furthermore, the protonated state of the drug enhanced its detachment from the polymer and subsequent dissolution in the medium. Contrastingly, higher pH values around the pKa of pyridine nitrogen strongly suppressed the dissolution in an exponential-like manner. This suggests that in addition to dissociating both linked polymers or dissolving one polymer group, active groups that facilitate hydrogen bonding can also play an important role in the release mechanism.
Asunto(s)
Resinas Acrílicas/química , Loratadina/análogos & derivados , Polímeros/química , Povidona/química , Portadores de Fármacos/química , Enlace de Hidrógeno , Concentración de Iones de Hidrógeno , Loratadina/química , SolubilidadRESUMEN
Although the non-conventional dosage forms (e.g. modified release per oral systems or transdermal patches) have more significant advantages than other conventional dosage forms, the pa- tients have to apply them correctly in their home medicine using to reach the effective and safe therapy. A guideline of relevant application instructions contribute to development of an effective pharmaceutical counseling in community pharmacies. The counseling and advices can improve the patients' knowledge concerning application rules of different new dosage forms (health- literacy) with patient adherence. Finally it will result more effective and safer therapies. The aim of our Hungarian questionnaire surveys was to explore the patients' drug application habits or application errors and improve special verbal counseling of mentioned non-conventional dosage forms in community pharmacies. Understandable patient information leaflets were developed about application rules and besides the levels of patients' reading comprehension was evaluated in case of the leaflet of medicinal patches. The results show that a properly developed text is useful for the majority of patients but they need the verbal explanation as well, moreover there is a demand for the verbal counseling in community pharmacies. The most common application errors were explored and the most effective instructions or application rules were collected for the pharmacists and patients concerning the modified release tablets or capsules and transdermal patches.
Asunto(s)
Servicios Comunitarios de Farmacia , Consejo , Alfabetización en Salud , Cumplimiento de la Medicación , Educación del Paciente como Asunto , Preparaciones Farmacéuticas/administración & dosificación , Farmacéuticos , Rol Profesional , Comprensión , Formas de Dosificación , Humanos , Hungría , Folletos , Preparaciones Farmacéuticas/química , Encuestas y CuestionariosRESUMEN
During the last decade, the formulation of nanofibrous materials loaded with different drugs for biomedical applications has evoked considerable interest. The large specific surface area, the special micro- and macrostructure of fiber mats, the possibility for gradual release and site-specific local delivery of the active compounds lead to cytotoxicity decrease and enhancement of the therapeutic effect of drugs and implants. The present review details the different spinning techniques applied for the design of micro- and nanofibrous drug delivery systems. It furthermore deals with the use of various polymers that are capable for the formation of fiber scaffolds of various biomedical applications.
Asunto(s)
Polímeros/química , Ingeniería de Tejidos/métodos , Sistemas de Liberación de Medicamentos , Humanos , Medicina RegenerativaRESUMEN
One of the promising approaches to predict in vivo disintegration time of orally disintegrating tablets (ODT) is the use of texture analyzer instrument. Once the method is able to provide good in vitro in vivo correlation (IVIVC) in the case of different tablets, it might be able to predict the oral disintegration time of similar products. However, there are many tablet parameters that influence the in vivo and the in vitro disintegration time of ODT products. Therefore, the measured in vitro and in vivo disintegration times can occasionally differ, even if they coincide in most cases of the investigated products and the in vivo disintegration times may also change if the aimed patient group is suffering from a special illness. If the method is no longer able to provide good IVIVC, then the modification of a single instrumental parameter may not be successful and the in vitro method must be re-set in a complex manner in order to provide satisfactory results. In the present experiment, an optimization process was developed based on texture analysis measurements using five different tablets in order to predict their in vivo disintegration times, and the optimized texture analysis method was evaluated using independent tablets.
Asunto(s)
Química Farmacéutica/métodos , Composición de Medicamentos/métodos , Preparaciones Farmacéuticas/química , Administración Oral , Química Farmacéutica/instrumentación , Composición de Medicamentos/instrumentación , Excipientes/química , Preparaciones Farmacéuticas/administración & dosificación , Comprimidos , Factores de TiempoRESUMEN
Water contents of superdisintegrant pharmaceutical excipients were determined by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy using simple linear regression. Water contents of the investigated three common superdisintegrants (crospovidone, croscarmellose sodium, sodium starch glycolate) varied over a wide range (0-24%, w/w). In the case of crospovidone three different samples from two manufacturers were examined in order to study the effects of different grades on the calibration curves. Water content determinations were based on strong absorption of water between 3700 and 2800 cm⻹, other spectral changes associated with the different compaction of samples on the ATR crystal using the same pressure were followed by the infrared region between 1510 and 1050 cm⻹. The calibration curves were constructed using the ratio of absorbance intensities in the two investigated regions. Using appropriate baseline correction the linearity of the calibration curves was maintained over the entire investigated water content regions and the effect of particle size on the calibration was not significant in the case of crospovidones from the same manufacturer. The described method enables the water content determination of powdered hygroscopic materials containing homogeneously distributed water.
Asunto(s)
Excipientes/química , Higroscópicos/química , Espectroscopía Infrarroja por Transformada de Fourier , Tecnología Farmacéutica/métodos , Agua/análisis , Calibración , Carboximetilcelulosa de Sodio/química , Química Farmacéutica , Modelos Lineales , Tamaño de la Partícula , Povidona/química , Polvos , Espectroscopía Infrarroja por Transformada de Fourier/normas , Almidón/análogos & derivados , Almidón/químicaRESUMEN
The purpose of the present study was to examine how the colloid stability features of o/w parenteral nutrition emulsions made with SMOFlipid (lipid emulsion based on soybean oil, medium chain triglycerides, olive oil and fish oil) will change in the presence of high concentration of calcium and glucose if usual micronutrients are also present, according to the needs of the clinical nutrition patient. Particle size analysis, zeta potential, dynamic surface tension measurements and light microscopic screening were carried out to evaluate the possible changes in the kinetic stability of the emulsions. Our results indicate that the higher glucose concentration of 15 or 20% could not compensate the emulsion-destabilizing effect of higher (5 mM) calcium concentration even in the presence of a modern fat emulsion. Therefore calcium demand of undernourished patient requiring 5 mM or higher final Ca²âº content in nutrient solution should be supplemented in another way.
Asunto(s)
Gluconato de Calcio/química , Glucosa/química , Aceites/química , Soluciones para Nutrición Parenteral/química , Agua/química , Química Farmacéutica , Coloides , Composición de Medicamentos , Estabilidad de Medicamentos , Cinética , Tamaño de la Partícula , Tensión Superficial , Tensoactivos/química , Tecnología Farmacéutica/métodosRESUMEN
OBJECTIVE: We analyzed the predictability of the United States Food and Drug Administration's Medwatch safety alerts on monoclonal antibodies with the aim of assessing the adequacy of their pre-approval safety evaluation. METHODS: An alert was considered observed when increased frequency, severity, or other new properties were reported for previously identified suspected adverse reactions. RESULTS: Up until January 2010, 36 safety alerts to mAbs were issued containing 61 alert terms. Just above a half (32) of the alert terms were assessed as observed. DISCUSSION: In addition to the observed reactions, a large proportion of unobserved reactions could have been predicted based on the mechanism of action and antibody target. Although retrospective assessment necessarily implies an element of subjectivity, there appears to be room for improvement in predicting adverse reactions to mAbs. CONCLUSIONS: Adverse reaction risk management and pharmaceutical care must focus on the observed reactions, but all effort should be made to extrapolate from the observed reactions to predict further safety issues. This should be taken into account by marketing authorization holders, prescribers, clinical trial sponsors, investigators and regulators.
Asunto(s)
Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Anticuerpos Monoclonales/efectos adversos , Gestión de Riesgos/métodos , Humanos , Índice de Severidad de la Enfermedad , Estados Unidos , United States Food and Drug AdministrationRESUMEN
AIM: This study is aimed at conducting a program for two different anesthetic methods used during a spinal fusion surgery to ensure better intra-operative hemodynamic stability and post-operative pain control. METHODS: A prospective, randomized, double blind study in patients scheduled for spinal fusion surgery, who were randomly allocated to two groups, G1 and G2, (n = 15 per group), class I-II ASA, was carried out. Both groups received pre-operatively midazolam, followed intra-operatively by propofol, sevoflurane, atracurium, and either remifentanil infusion 0.2 microg/kg/min (G1), or the same dose of remifentanil infusion and low doses of ketamine infusion 1 microg/kg/min (G2) anesthetics, antidote medication and post-operative morphine doses. HR, MAP, vital signs, surgical bleeding, urine output, duration of surgery and duration of anesthesia were recorded. In a 24-h recovery period in a post-anesthesia care unit (PACU) the recovery time, the first pain score and analgesic requirements were measured. RESULTS: Intra-operative HR and arterial BP were significantly less (p < 0.05) in G1 as compared to G2. In the PACU the first pain scores were significantly less (p < 0.05) in G2 than in G1. The time for the first patient analgesia demand dose was greater in G2, as also morphine consumption which was greater in G1 than G2 (p < 0.05). Other results were the same. None of the patients had any adverse drug reaction. CONCLUSIONS: Adding low doses of ketamine hydrochloride could be a routine therapy to improve the hemodynamic stability and reduce the post-operative morphine consumption during spinal fusion surgery.
Asunto(s)
Anestésicos Combinados/uso terapéutico , Ketamina/uso terapéutico , Piperidinas/uso terapéutico , Fusión Vertebral/métodos , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Periodo de Recuperación de la Anestesia , Anestésicos Disociativos/uso terapéutico , Anestésicos Intravenosos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Método Doble Ciego , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Morfina/administración & dosificación , Morfina/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Estudios Prospectivos , RemifentaniloRESUMEN
The physical stability of two types of MCT-emulsions made by different technologies - physical mixture vs. structured lipids - was studied as a function of storage time and temperature. Particle size analysis, zeta potential and dynamic surface tension measurements were carried out to evaluate the possible changes in the kinetic stability of the emulsions. Our results indicate that the physical mixture technology of MCT-emulsions resulted in impaired physicochemical stability compared to the ones containing structured triglycerides. In the case of structured lipids, both medium and long chain fatty acids can be found in one triglyceride molecule, leading to a favorable interfacial location of structured triglycerides. Besides the advantageous metabolic effects of structured triglycerides, their application is recommended to improve the physical stability of TPN admixtures.
Asunto(s)
Fenómenos Químicos , Emulsiones/química , Lípidos/química , Fosfolípidos/química , Sorbitol/química , Análisis de Varianza , Combinación de Medicamentos , Tamaño de la Partícula , Tensión SuperficialRESUMEN
The purpose of the present study was to formulate a novel thermoresponsive membrane controlled therapeutic system from Metolose for possible transdermal application. Metolose gel shows thermal gelation property, which can be characterized by two (T(1), T(2)) temperatures. A sharp decrease of viscosity can be measured at T(1), but gelation can be observed at T(2). Different types of Metolose polymers were compared considering their thermoresponsive behaviour. Only thermal gelation was observed in the case of Metolose SM, while Metolose SH showed a sudden decrease of viscosity at T(1). Since this temperature is above the body temperature, so it should be shifted to the skin temperature in case of possible transdermal application. Modulation of thermoresponsibility was followed by rheological method, and the thermoresponsive drug release from Metolose gel was studied by static liberation test. Our results demonstrated that the effect of different salts (NaCl, NaHCO(3), KCl) of various concentrations in Metolose SH gel reduced T(1) to the skin temperature, which enabled enhanced drug release.
Asunto(s)
Sistemas de Liberación de Medicamentos , Metilcelulosa/administración & dosificación , Piel/metabolismo , Administración Cutánea , Geles , Metilcelulosa/química , Solubilidad , Temperatura , ViscosidadRESUMEN
Transdermal therapeutic systems (TTSs) were studied applying different sucrose fatty acid esters (SEs) as drug delivery agents. Matrix and membrane controlled TTSs were prepared and compared. Membrane was made from a methacrylic polymer (Eudragit NE) of pH independent permeability which can achieve diffusion controlled drug liberation. Model drug was a water soluble beta-blocker, metoprolol, which has short biological half-life, so applying it in a TTS, the duration of its action could be prolonged. Sucrose fatty acid esters of different fatty acid chain lengths and consequently different hydrophilic-lipophilic balance (HLB) values were studied considering their effect on the metoprolol release from TTSs. Different mathematical models were applied for the evaluation of the release process. The results of the in vitro studies indicated that SEs of shorter fatty acid chain length and higher HLB value increased the amount of released drug about 10 times. SEs could be promising agents in transdermal therapeutic systems to control the drug release and cutaneous absorption.
Asunto(s)
Administración Cutánea , Ácidos Grasos/química , Sacarosa/química , Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas Adrenérgicos beta/química , Antagonistas Adrenérgicos beta/farmacocinética , Ésteres , Ácidos Grasos/farmacología , Semivida , Membranas Artificiales , Metoprolol/administración & dosificación , Metoprolol/química , Metoprolol/farmacocinética , Modelos Estadísticos , Ácidos Polimetacrílicos , Absorción Cutánea/efectos de los fármacos , Espectrofotometría Ultravioleta , Relación Estructura-Actividad , Sacarosa/farmacologíaRESUMEN
The plasticizing effects of poly(ethylene glycol) (PEG 400) on methylcellulose (Metolose) cast films were studied by conventional physicochemical methods and positron annihilation spectroscopy. The PEG concentrations relative to the total polymer content were varied within the range 0-75% (w/w). At low concentrations (below 33.3%, w/w), the plasticizer was found to build in into the methylcellulose structure. On the other hand, at higher concentrations (above 50%, w/w), it formed small separate phases in the films. Positron annihilation spectroscopy (PALS) was applied to track the Metolose-PEG interaction. Controlled ageing of Metolose-PEG films at room temperature and at 75% RH revealed a significant difference between the ageing processes of the monophase and those of the separate phase films. The ageing involves two steps in both cases: a fast and a slow one. The PALS measurements demonstrated that the slow process is hindered in the phase-separated samples.
Asunto(s)
Metilcelulosa/química , Plastificantes/química , Polietilenglicoles/química , Polímeros/química , Elasticidad , Estructura Molecular , Análisis Espectral/métodos , TemperaturaRESUMEN
Molar refraction as well as refractive index has many uses. Beyond confirming the identity and purity of a compound, determination of molecular structure and molecular weight, molar refraction is also used in other estimation schemes, such as in critical properties, surface tension, solubility parameter, molecular polarizability, dipole moment, etc. In the present study molar refraction values of polymer dispersions were determined for the quantitative estimation of film forming polymer-plasticizer interactions. Information can be obtained concerning the extent of interaction between the polymer and the plasticizer from the calculation of molar refraction values of film forming polymer dispersions containing plasticizer.
Asunto(s)
Plastificantes/química , Polímeros/química , Refractometría , Química Farmacéutica , Ácidos Dicarboxílicos/química , Modelos Químicos , Polietilenglicoles/química , Ácidos Polimetacrílicos/química , Triacetina/químicaRESUMEN
Previous studies have confirmed that the phase transition of vesicular gels of hydrogenated phospholipids to the less ordered fluid vesicular state was induced by the increase of the beta-sitosterol ratio in the whole gel system and consequently in the lipid bilayer. The purpose of the present study was to evaluate the influence of the beta-sitosterol portion in the lipid bilayer and the effect of high pressure homogenization on the structural characteristics of the prepared gel systems. In addition the influence of beta-sitosterol on the consequent chlorhexidine release from the obtained vesicles and liposomes was also examined. Lipid mixtures were prepared from different molar ratios of lecithin:sterol components (90:10-65:35 mol%). The obtained mixtures were hydrated with the aqueous solution of chlorhexidine digluconate in order to achieve a 30% (w/w) final concentration of the lipid mixtures and a 4% (w/w) concentration of the drug. One portion of the resultant multilamellar vesicles was homogenized by using high pressure. To characterize the homogenized and non-homogenized systems, transmission electron microscopy of the freeze-fractured samples and differential scanning calorimetry (DSC) were carried out. A vertical type diffusion cell was applied to determine the amount of released chlorhexidine digluconate. Along with the increase in beta-sitosterol concentration, the fluidity of the membrane as well as its permeability also increased. The increased permeability--caused by the higher beta-sitosterol concentration--and the high pressure homogenization, which increased the dispersity and therefore the surface area, enabled a higher amount of chlorhexidine to be released. The increase of drug release was more pronounced in the case of samples prepared with high pressure homogenization.
Asunto(s)
Antiinfecciosos Locales/química , Clorhexidina/química , Composición de Medicamentos/métodos , Hipolipemiantes/química , Liposomas , Sitoesteroles/química , Rastreo Diferencial de Calorimetría , Preparaciones de Acción Retardada , Geles , Membrana Dobles de Lípidos/química , Microscopía Electrónica de TransmisiónRESUMEN
The rate and extent of drug release from the most controlled release wax matrices are influenced by the drug loading/embedding excipient ratio of the systems. In the present study hydrophobic wax - zinc sulphate matrices with different drug loadings were prepared for the therapy of Wilson's disease. The drug release was tested by the paddle method of USP and the dissolution data were analysed. Both the dissolution rate and kinetic profile can be controlled by alteration in the quantity of embedding material. Matrices of 75% zinc sulphate loadings showed steady state diffusion-controlled matrix release with good correlation in vitro. Good absorption of zinc sulphate from the gastrointestinal tract was proven by significant elevation of serum zinc level in patients with Wilson's disease.
Asunto(s)
Degeneración Hepatolenticular/tratamiento farmacológico , Sulfato de Zinc/administración & dosificación , Sulfato de Zinc/uso terapéutico , Absorción , Algoritmos , Cápsulas , Química Farmacéutica , Excipientes , Cinética , Lípidos/química , Modelos Químicos , Porosidad , Solubilidad , Ceras , Sulfato de Zinc/químicaRESUMEN
Migration of plasticizers from film coating polymers towards the core and to the storage medium could result in serious changes in the mechanical properties and permeability of coatings thus greatly influencing rate and extent of drug release. The purpose of the present study was to follow the migration of water soluble triethyl citrate applied as a plasticizer in Acryl-Eze coating by Gas Chromatography/Mass Spectrometry (GC/MS). 20%w/w Acryl-Eze dispersions containing triethyl citrate of different concentrations were prepared. Placebo tablets were compressed and coated with the prepared dispersions. The coated tablets were stored under different relative humidity conditions for different time intervals. Considerable migration of triethyl citrate towards the tablet cores was found. The extent of the triethyl citrate migration was influenced by the relative humidity of the storage medium.
Asunto(s)
Citratos/química , Plastificantes/química , Polímeros/química , Composición de Medicamentos , Humedad , Comprimidos RecubiertosRESUMEN
Hydrophobic zinc sulphate wax matrices with different drug loadings were prepared for the individual hospital therapy of Wilson's disease. The drug release parameters, scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) of the samples were analysed. The release mechanisms from matrices of 75% and 80% w/w zinc sulphate loadings were described with good correlation by the semi-empirical Fikkian diffusion based release model. Besides the zinc sulphate diffusion through the pores of the wax matrices, the parallel diffusion of zinc sulphate from the matrix surface is dominant in the case of samples of 83% and 90%w/w drug loadings. The combination of SEM and EDS analysis visualizes the morphology of the matrices and the related composition thus explaining the differences in the release characteristics.
Asunto(s)
Degeneración Hepatolenticular/tratamiento farmacológico , Sulfato de Zinc/administración & dosificación , Sulfato de Zinc/uso terapéutico , Algoritmos , Preparaciones de Acción Retardada , Excipientes , Microscopía Electrónica de Rastreo , Espectrometría por Rayos X , CerasRESUMEN
Previous studies confirm that beta-sitosterol is very effective in altering the molecular packing of soybean lecithin bilayers even more than the cholesterol. The primary aim of the present study was to evaluate the influence of the beta-sitosterol portion in the lipid bilayer on the physical-chemical characteristics of the prepared gel systems, and its influence on the consequent drug release from the liposomes obtained from vesicular phospholipid gels (VPG-s) by redispersion. VPG-s were prepared of different molar ratios of lecithin:sterol components (10:90-35:65 mol%). The mixture was hydrated with the aqueous solution of chlorhexidin digluconate in order to achieve 30% (w/w) final concentration of the lipid mixtures and 4% (w/w) concentration of the drug in each homogenized VPG sample. To characterize the obtained VPG systems optical microscopic examinations using polarized light, differential scanning calorimetry (DSC), photon correlation spectroscopy (PCS), and dynamic surface tension measurements were carried out. Vertical type diffusion cell was applied to determine the amount of released chlorhexidine digluconate. As a result of the surface tension-decreasing effect of beta-sitosterol, the membrane deformability and the dispersity of the system increased. The increased dispersity and fluidity significantly increased the extent of released chlorhexidine from the vesicles.