Dissolution parameters for sodium diclofenac-containing hypromellose matrix tablet

Sodium diclofenac (SD) release from dosage forms has been studied under different conditions. However, no dissolution method that is discriminatory enough to reflect slight changes in formulation or manufacturing process, and which could be effectively correlated with the biological properties of the dosage form, has been reported. This study sought to develop three different formulae of SD-containing matrix tablets and to determine the effect of agitation speed in its dissolution profiles. F1, F2 and F3 formulations were developed using hypromellose (10, 20 and 30%, respectively for F1, F2 and F3) and other conventional excipients. Dissolution tests were carried out in phosphate buffer pH 6.8 at 37 degrees C using apparatus 11 at 50, 75 or 100 rpm. Dissolution efficiency (DE), T(50) and T(90) were determined and plotted as functions of the variables agitation speed and hypromellose concentration. Regarding DE, F2 showed more sensitivity to variations in agitation speed than F1 and F3. Increasing hypromellose concentration reduced DE values, independent of agitation speed. Analysis of T(50) and T(90) suggests that F1 is less sensitive to variations in agitation speed than F2 and F3. Most discriminatory dissolution conditions were observed at 50 rpm. Results suggest that the comparison of dissolution performance of SD matrix tablets should take into account polymer concentration and agitation conditions. (C) 2009 Published by Elsevier B.V.

Simultaneous determination of econazole nitrate, main impurities and preservatives in cream formulation by high performance liquid chromatography

A reversed-phase high performance liquid chromatographic (RP-HPLC) method for determination of econazole nitrate, preservatives (methylparaben and propylparaben) and its main impurities (4-chlorobenzl alcohol and alpha-(2,4-dicholorophenyl)-1H-imidazole-1-ethanol) in cream formulations, has been developed and validated. Separation was achieved on a column Bondclone (R) C18 (300 mm x 3.9 mm i.d., 10 mu m) using a gradient method with mobile phase composed of methanol and water. The flow rate was 1.4 mL min(-1), temperature of the column was 25 C and the detection was made at 220 nm. Miconazole nitrate was used as an internal standard. The total run time was less than 15 min, The analytical curves presented coefficient of correlation upper to 0.99 and detection and quantitation limits were calculated for all molecules. Excellent accuracy and precision were obtained for econazole nitrate. Recoveries varied from 97.9 to 102.3% and intra- and inter-day precisions, calculated as relative standard deviation (R.S.D), were lower than 2.2%. Specificity, robustness and assay for econazole nitrate were also determined. The method allowed the quantitative determination of econazole nitrate, its impurities and preservatives and could be applied as a stability-indicating method for econazole nitrate in cream formulations. (C) 2008 Elsevier B.V. All rights reserved.

Spectrophotometric determination of fenoterol hydrobromide in pharmaceutical preparations

A simple spectrophotometric method has been developed,for the determination of fenoterol hydrobromide (FH) in tablets, drops and syrup, as the only active principle and associated with ibuprofen. The method is based on the oxidative coupling reaction of the FH with 3-methyl-2-benzothiazolinone hydrazone (MBTH) and ceric sulphate as oxidant reagent. The mixture of the drug, MBTH and ceric sulfate, in acid medium, produces a red brown color compound, with absorption maximum at 475 nm. The calibration curve was linear over a concentration range from 3.0 to 12.0 mu g/mL, with correlation coefficient of 0.9998. The different experimental parameters affecting the development and stability of the color compound were carefully studied and optimized. The method was applied successfully to assay FH in dosage forms and simulated samples. The coefficient of variation was from 0.25 % to 0.82 % and average recoveries of the standard from 98 % to 102 %. The excipients (tablets and drops) did not interfere in the analysis and the results showed that method can be used for determination of the FH isolated or associated with ibuprofen with precision, accuracy and specificity. In case of syrup, the interference in the analysis suggests a possible reaction between vehicle components with MBTH.

A new approach to the granulation of beta-cyclodextrin inclusion complexes

Cyclodextrins (CDs) are annular oligosaccharides containing 6-12 glucose unities joined together by alpha-1,4 bonds. They have a conical-truncated shape with a lipophilic cavity in which different molecules can be included resulting in a stable inclusion complex. The cyclodextrins have been widely applied in pharmaceutical technology with the objective of increasing the solubility, stability and bioavailability of drugs in different pharmaceutical dosage forms, such as tablets. In order to obtain beta-CD tablets, liquid dispersions of drug/beta-CD are usually submitted to different drying processes, like spray-drying, freeze-drying or slow evaporation, being this dry material added to a number of excipients. However, such drying processes can generate particulate materials showing problems of flow and compressibility, needing their conversion into granulates by means of wetting with granulation liquid followed by additional drying. In this work, the main objective was to evaluate the preparation of tablets without the need of this additional drying step. For this purpose an aqueous dispersion containing acetaminophen/beta-CD complex and cornstarch was dried using a spouted bed and the obtained granules were compressed in tablets. Acetaminophen was used as model drug due to its low water solubility and the inexpensive and widely available cornstarch was chosen as excipient. Acetaminophen powder was added into a beta-cyclodextrin solution prepared in distilled water at 70 degrees C. Stirring was kept until this dispersion cooled to room temperature. Then cornstarch was added and the resulting dispersion was dried in spouted bed equipment. This material was compressed into tablets using an Erweka Korsh EKO tablet machine. This innovative approach allowed the tablets preparation process to be carried out with fewer steps and represents a technological reliable strategy to produce beta-cyclodextrin inclusion complexes tablets. (C) 2010 Elsevier By. All rights reserved.

Determination of pharmocotherapeutical complexity in institutionalized elderly

The phenomenon of aging is nowadays society as acquired the status of a social problem, with growing attention and concern, leading to an increase number of studies dedicated to the elderly. The lack of domestic, familiar or social support often lead elderly to nursing homes. Institutionalization is in many cases the only opportunity to have access to health care and life quality. Aging is also associated with a higher prevalence of chronic diseases that require long term medication sometimes for life. Frequently the onset of multiple pathologies at the same time require different therapies and the phenomenon of polypharmacy (five ou more drugs daily) can occur. Even more, the slow down of physiological and cognitives mechanisms associated with these chronic diseases can interphere, in one hand, with the pharmacocinetic of many medications and, on the other hand, with the facility to accomplish the therapeutical regimen. All of these realities contribute to an increase of pharmacotherapeutical complexity, decreasing the adherence and effectiveness of treatment. The pharmacotherapeutical complexity of an individual is characterized by the conciliator element of different characteristics of their drug therapy, such as: the number of medications used; dosage forms; dosing frequency and additional indications. It can be measured by the Medication Regimen Complexity Index (MRCI), originally validated in English.

Flow injection electrochemical determination of apomorphine

Few analytical methods are currently available for determination of apomorphine, the active substance of a new oral formulation used in the treatment of erectile dysfunction. In this way a flow injection electrochemical method (FIA-EC) was developed for its quantification and applied to pharmaceutical dosage forms. Based in previous findings regarding the stability of apomorphine in borate buffer and after optimization of several analytical parameters a single channel flow injection manifold was set up that enables the determination of this drug over the concentration range of 3 to 16 µmol L-1 with a detection limit of 0.5 µmol L-1 at a sampling rateof 90 h-1. The simplicity and rapidity of the FIA-EC method used, its reproducibility and sensitivity make it suitable for quality control of pharmaceutical preparations of apomorphine intended for clinical use and research.

Strategies for price reduction of HIV medicines under a monopoly situation in Brazil

ABSTRACT OBJECTIVE To analyze Government strategies for reducing prices of antiretroviral medicines for HIV in Brazil. METHODS Analysis of Ministry of Health purchases of antiretroviral medicines, from 2005 to 2013. Expenditures and costs of the treatment per year were analyzed and compared to international prices of atazanavir. Price reductions were estimated based on the terms of a voluntary license of patent rights and technology transfer in the Partnership for Productive Development Agreement for atazanavir. RESULTS Atazanavir, a patented medicine, represented a significant share of the expenditures on antiretrovirals purchased from the private sector. Prices in Brazil were higher than international references, and no evidence was found of a relationship between purchase volume and price paid by the Ministry of Health. Concerning the latest strategy to reduce prices, involving local production of the 200 mg capsule, the price reduction was greater than the estimated reduction. As for the 300 mg capsule, the amounts paid in the first two years after the Partnership for Productive Development Agreement were close to the estimated values. Prices in nominal values for both dosage forms remained virtually constant between 2011 (the signature of the Partnership for Productive Development Agreement), 2012 and 2013 (after the establishment of the Partnership). CONCLUSIONS Price reduction of medicines is complex in limited-competition environments. The use of a Partnership for Productive Development Agreement as a strategy to increase the capacity of local production and to reduce prices raises issues regarding its effectiveness in reducing prices and to overcome patent barriers. Investments in research and development that can stimulate technological accumulation should be considered by the Government to strengthen its bargaining power to negotiate medicines prices under a monopoly situation.

Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus SEMICYUC-SENPE: Septic patient

Nutritional metabolic management, together with other treatment and support measures used, is one of the mainstays of the treatment of septic patients. Nutritional support should be started early, after initial life support measures, to avoid the consequences of malnutrition, to provide adequate nutritional intake and to prevent the development of secondary complications such as superinfection or multiorgan failure. As in other critically-ill patients, when the enteral route cannot be used to ensure calorie-protein requirements, the association of parenteral nutrition has been shown to be safe in this subgroup of patients. Studies evaluating the effect of specific pharmaconutrients in septic patients are scarce and are insufficient to allow recommendations to be made. To date, enteral diets with a mixture of substrates with distinct pharmaconutrient properties do not seem to be superior to standard diets in altering the course of sepsis, although equally there is no evidence that these diets are harmful. There is insufficient evidence to recommend the use of glutamine in septic patients receiving parenteral nutrition. However, given the good results and absence of glutamine-related adverse effects in the various studies performed in the general population of critically-ill patients, these patients could benefit from the use of this substance. Routine use of omega-3 fatty acids cannot be recommended until further evidence has been gathered, although the use of lipid emulsions with a high omega-6 fatty acid content should be avoided. Septic patients should receive an adequate supply of essential trace elements and vitamins. Further studies are required before the use of high-dose selenium can be recommended.

Historia de la alimentación parenteral; primera lección Jesús Culebras

Artículo histórico. Texto de la “Primera lección Jesús Culebras” dictada en el XXV Congreso Nacional de SENPE, Badajoz, 11-14 de mayo de 2010.

Listado de verificación de procedimientos invasivos en nefrología: catéter peritoneal, catéter venoso central temporal para hemodiálisis y biopsia renal percutánea

Sección "Buenas prácticas en gestión clínica"

Enhanced antitumor activity of doxorubicin in breast cancer through the use of poly(butylcyanoacrylate) nanoparticles.

The use of doxorubicin (DOX), one of the most effective antitumor molecules in the treatment of metastatic breast cancer, is limited by its low tumor selectivity and its severe side effects. Colloidal carriers based on biodegradable poly(butylcyanoacrylate) nanoparticles (PBCA NPs) may enhance DOX antitumor activity against breast cancer cells, thus allowing a reduction of the effective dose required for antitumor activity and consequently the level of associated toxicity. DOX loading onto PBCA NPs was investigated in this work via both drug entrapment and surface adsorption. Cytotoxicity assays with DOX-loaded NPs were performed in vitro using breast tumor cell lines (MCF-7 human and E0771 mouse cancer cells), and in vivo evaluating antitumor activity in immunocompetent C57BL/6 mice. The entrapment method yielded greater drug loading values and a controlled drug release profile. Neither in vitro nor in vivo cytotoxicity was observed for blank NPs. The 50% inhibitory concentration (IC50) of DOX-loaded PBCA NPs was significantly lower for MCF-7 and E0771 cancer cells (4 and 15 times, respectively) compared with free DOX. Furthermore, DOX-loaded PBCA NPs produced a tumor growth inhibition that was 40% greater than that observed with free DOX, thus reducing DOX toxicity during treatment. These results suggest that DOX-loaded PBCA NPs have great potential for improving the efficacy of DOX therapy against advanced breast cancers.

Immune cell impact of three differently coated lipid nanocapsules: pluronic, chitosan and polyethylene glycol.

Lipid nanocapsules (NCs) represent promising tools in clinical practice for diagnosis and therapy applications. However, the NC appropriate functionalization is essential to guarantee high biocompatibility and molecule loading ability. In any medical application, the immune system-impact of differently functionalized NCs still remains to be fully understood. A comprehensive study on the action exerted on human peripheral blood mononuclear cells (PBMCs) and major immune subpopulations by three different NC coatings: pluronic, chitosan and polyethylene glycol-polylactic acid (PEG) is reported. After a deep particle characterization, the uptake was assessed by flow-cytometry and confocal microscopy, focusing then on apoptosis, necrosis and proliferation impact in T cells and monocytes. Cell functionality by cell diameter variations, different activation marker analysis and cytokine assays were performed. We demonstrated that the NCs impact on the immune cell response is strongly correlated to their coating. Pluronic-NCs were able to induce immunomodulation of innate immunity inducing monocyte activations. Immunomodulation was observed in monocytes and T lymphocytes treated with Chitosan-NCs. Conversely, PEG-NCs were completely inert. These findings are of particular value towards a pre-selection of specific NC coatings depending on biomedical purposes for pre-clinical investigations; i.e. the immune-specific action of particular NC coating can be excellent for immunotherapy applications.

Le zinc viendra-t-il à bout du rhume?: revue Cochrane pour le praticien.

Cet article présente les résultats de la revue systématique: Singh M, Das RR. Zinc for the common cold. Cochrane Database of Systematic Reviews 2011, Issue 2, Art. No.: CD001364. DOI: 10.1002/14651858.CD001364.pub3. PMID: 21328251.

Nanoparticle Labels in Bioaffinity Assays

Nanoparticles offer adjustable and expandable reactive surface area compared to the more traditional solid phase forms utilized in bioaffinity assays due to the high surface to-volume ratio. The versatility of nanoparticles is further improved by the ability to incorporate various molecular complexes such as luminophores into the core. Nanoparticle labels composed of polystyrene, silica, inorganic crystals doped with high number of luminophores, preferably lanthanide(III) complexes, are employed in bioaffinity assays. Other label species such as semiconductor crystals (quantum dots) or colloidal gold clusters are also utilized. The surface derivatization of such particles with biomolecules is crucial for the applicability to bioaffinity assays. The effectiveness of a coating is reliant on the biomolecule and particle surface characteristics and the selected coupling technique. The most critical aspects of the particle labels in bioaffinity assays are their size-dependent features. For polystyrene, silica and inorganic phosphor particles, these include the kinetics, specific activity and colloidal stability. For quantum dots and gold colloids, the spectral properties are also dependent on particle size. This study reports the utilization of europium(III)-chelate-embedded nanoparticle labels in the development of bioaffinity assays. The experimental covers both the heterogeneous and homogeneous assay formats elucidating the wide applicability of the nanoparticles. It was revealed that the employment of europium(III) nanoparticles in heterogeneous assays for viral antigens, adenovirus hexon and hepatitis B surface antigen (HBsAg), resulted in sensitivity improvement of 10-1000 fold compared to the reference methods. This improvement was attributed to the extreme specific activity and enhanced monovalent affinity of the nanoparticles conjugates. The applicability of europium(III)-chelate-doped nanoparticles to homogeneous assay formats were proved in two completely different experimental settings; assays based on immunological recognition or proteolytic activity. It was shown that in addition to small molecule acceptors, particulate acceptors may also be employed due to the high specific activity of the particles promoting proximity-induced reabsorptive energy transfer in addition to non-radiative energy transfer. The principle of proteolytic activity assay relied on a novel dual-step FRET concept, wherein the streptavidin-derivatized europium(III)-chelate-doped nanoparticles were used as donors for peptide substrates modified with biotin and terminal europium emission compliant primary acceptor and a secondary quencher acceptor. The recorded sensitized emission was proportional to the enzyme activity, and the assay response to various inhibitor doses was in agreement with those found in literature showing the feasibility of the technique. Experiments regarding the impact of donor particle size on the extent of direct donor fluorescence and reabsorptive excitation interference in a FRET-based application was conducted with differently sized europium(III)-chelate-doped nanoparticles. It was shown that the size effect was minimal

Determinação de fármacos diuréticos em associação por cromatografia em camada delgada e espectrofotometria

A rapid, sensitive and reliable thin-layer chromatography/spectrophotometry screening procedure was developed for quantitative determination of diuretics associated in pharmaceutical dosage forms. The chromatographic method employed microcrystalline cellulose and butanol : acetic acid : water (4:1:1) or amilic alcohol : ammonium hydroxide 25% (9:1) as mobile phases and detection by U.V. light. The drugs were extracted using a simple procedure and were quantified by U.V. spectrophotometry. Results varied from 97.5 to 102.5% and are similar to those obtained by conventional methods. This method of quantification of diuretics is promising for quality control of drugs.