[Pharmaceutical counseling of non-conventional dosage forms concerning the health-literacy and the patient adherence in public medication dispensing -Questionnaire surveys in Hungarian community pharmacies.] / Not available.

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.

Predictability of serious adverse reaction alerts for monoclonal antibodies.

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.

Remifentanil in combination with ketamine versus remifentanil in spinal fusion surgery--a double blind study.

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.

Application of sucrose fatty acid esters in transdermal therapeutic systems.

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.

Potential application of Metolose in a thermoresponsive transdermal therapeutic system.

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.

Pharmaceutical counselling about different types of tablet-splitting methods based on the results of weighing tests and mechanical development of splitting devices.

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.

Effect of beta-sitosterol concentration and high pressure homogenization on the chlorhexidine release from vesicular gels.

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.

Quantitative estimation of film forming polymer-plasticizer interactions by the Lorentz-Lorenz Law.

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.

Metolose-PEG interaction as seen by positron annihilation spectroscopy.

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.

Carbopol®-crospovidone interpolymer complex for pH-dependent desloratadine release.

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.

Kinetic study of zinc sulphate release from lipophilic matrices prepared for the therapy of Wilson's disease.

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.

Polymers and formulation strategies of nanofibrous systems for drug delivery application and tissue engineering.

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.

Fractures of the base of the fifth metatarsal distal to the tuberosity. Classification and guidelines for non-surgical and surgical management.

Between 1973 and 1982 forty-six fractures of the base of the fifth metatarsal, distal to the tuberosity, were treated and followed for a mean of forty months (range, six to 108 months). Roentgenographic criteria were used to define three types of fractures: acute fractures characterized by a narrow fracture line and absence of intramedullary sclerosis; those with delayed union, with widening of the fracture line and evidence of intramedullary sclerosis; and those with non-union and complete obliteration of the medullary canal by sclerotic bone. Of the twenty-five acute fractures in this series, fifteen were treated with a non-weight-bearing toe-to-knee cast, and fourteen of them healed in a mean of seven weeks. Only four of the other ten, which were treated with various weight-bearing methods, progressed to union. Of the twelve patients with delayed union, one refused treatment, one was treated with a bone graft, and ten were treated initially by immobilization of the limb in a plaster cast and weight-bearing. Of these ten fractures, seven healed in a mean of 15.1 months and three eventually required grafting for non-union. Of the nine non-unions in the series, which were treated primarily with medullary curettage and bone-grafting, eight healed in a mean of three months. In all, twenty fractures were treated surgically with an autogenous corticocancellous graft that was inlaid after thorough curettage and drilling of the sclerotic bone that obliterated the intramedullary cavity. Of these twenty fractures, nineteen progressed to complete healing and one, to asymptomatic non-union.(ABSTRACT TRUNCATED AT 250 WORDS)

Proximal diaphyseal fractures of the fifth metatarsal--treatment of the fractures and their complications in athletes.

Twenty-one patients (age range, 15 to 26; 18 patients 15 to 20 years old) had proximal diaphyseal fractures of the fifth metatarsal. Clinical records and radiographs for all patients were available for review. Patient treatment had been individualized and included several methods, including rest, plaster immobilization, and bone grafting. Twenty of the 21 patients were boys or men participating in athletics. Nine of the 21 fractures and 8 of the reinjuries were sustained while playing basketball. Healing required a minimum of 3 months (with bone graft) and some fractures were not radiographically healed at 20 months, although the patients were clinically asymptomatic. The fracture of the proximal shaft of the fifth metatarsal, particularly the 1.5-cm segment distal to the tuberosity, is a troublesome injury in the active athlete. The clinical course does not appear to be influenced by the usual initial conservative treatment modalities, although many of these fractures will heal if the athlete is willing to restrict activities for a prolonged period of time. In this series, bone grafting with a tibial corticocancellous graft after thorough curettage of sclerotic bone obliterating the medullary canal was the most effective treatment modality for delayed union.

Effect of beta-sitosterol on the characteristics of vesicular gels containing chlorhexidine.

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.

Influence of chlorhexidine species on the liquid crystalline structure of vehicle.

The aim of this study was to investigate the influence of three chlorhexidine species, chlorhexidine base and its salts (diacetate and digluconate), on the physico-chemical features of liquid crystalline systems and on drug transport through lipophilic membranes. Nonionic surfactant, Synperonic A7 (PEG(7)-C(13--15)) was selected for the preparation of the liquid crystalline systems. Mixtures of different ratios of Synperonic A7 and water were prepared. The liquid crystalline systems were characterized using polarizing microscopy, small-angle neutron scattering and transmission electron microscopy. Membrane transport was also examined. The addition of chlorhexidine species to the liquid crystalline system modified the structure of the liquid crystalline system. As a result of liquid crystal--drug interaction, the solubility of chlorhexidine base and its diffusion through lipophilic membranes increased in comparison with those of the chlorhexidine salts.

The effect of liquid crystalline structure on chlorhexidine diacetate release.

The aim of this study was to examine different liquid crystalline preparations containing chlorhexidine diacetate and to find connection between their structure and the kinetic of drug release. Nonionic surfactant, Synperonic A7 (PEG(7)-C(13-15)) was selected for the preparation of the examined liquid crystalline systems. Mixtures of different ratios of Synperonic A7 and water were produced. By increasing the water content of the systems, lamellar and hexagonal liquid crystal structures were observed. For the analysis of the prepared liquid crystalline systems polarising microscopy, rheology study, differential scanning calorimetry and dynamic swelling tests were carried out. The chlorhexidine diacetate release was examined by Franz-type vertical diffusion cell apparatus. The chlorhexidine diacetate release from hexagonal liquid crystalline preparations was characterised by zero-order release kinetics, while the drug release from lamellar liquid crystalline systems was described by anomalous (non-Fickian) transport. The results indicate that the drug release kinetic is strongly dependent on the liquid crystalline structure.

Effect of particle size and coating level on the diffuse reflectance of wax matrices.

The aim of this study was to examine the influence of particle size and extent of coating on the diffuse-reflectance spectra of wax matrices containing embedded potassium chloride. Near-infrared spectroscopy was used to analyse the diffuse-reflectance characteristics of the prepared multi-particulate matrices without destructive sample preparation. A 2-factor, 3-level face-centred central composite design was selected to construct a second-order polynomial model which described the effect of particle size and amount of coating on the intensity of the diffusely reflected light. A non-linear model was used to demonstrate the effect of the selected parameters on the intensity of the reflected light; good correlation was obtained between experimental and predicted results. The results indicated that the extent of coating and the particle size of the examined systems in the selected particle size-range modified the intensity of the reflected light. It can be concluded that near-infrared spectroscopy is a sensitive means of measuring not only the particle size of powders (substrates and their mixtures), but also that of coated multi-particulate systems.

The effect of surfactant and suspending agent concentration on the effective particle size of metered-dose inhalers.

The aim of this study was to examine the influence of the concentrations of surfactant and suspending agent on the quantity of effective particles (size < 10 microm) delivered by metered-dose inhalers. A 2-factor, 3-level, face-centred central composite design was used to construct a second-order polynomial model which describes the effect of formulation factors (suspending agent, surface-active ingredient) on the therapeutically important characteristic (effective particle size) delivered by metered-dose inhalers. Oleic acid was selected as the surface-active ingredient, and the suspending agent was anhydrous alcohol. A non-linear model demonstrated with good correlation the effect of the amounts of surfactant and suspending agent on the quantity of particles of effective size. The results obtained enable determination of the correct amount of surface-active ingredient and the optimum quantity of the suspending agent, thus enabling formulation of a therapeutically effective formulation.

Study of triethyl citrate migration from coating polymers to tablet cores.

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.