[Therapeutic education for cardiac failure patients: the I-care programme]. / Education thérapeutique des patients insuffisants cardiaques: le programme I-care.

Therapeutic education is becoming increasingly important in the management of chronic diseases including cardiac failure. The I-CARE programme consists of an evaluation of the role of therapeutic education in France, creating standardised tools and setting up training sessions for therapeutic education in the context of cardiac failure. Approximately two thirds of the French centres contacted perform therapeutic education with their available means. The lack of personnel, space, and training tools represent obstacles to the development of therapeutic education. The tools developed in the programme fall into 5 areas: diagnosis education, understanding the illness, diet, physical activity/daily life, and treatment. Training sessions were organised for the teams, consisting of at least one cardiologist and nurse. The I-CARE programme should allow the expansion of therapeutic education for cardiac failure and improve the multidisciplinary management of this disease which increasingly affects often elderly subjects.

[Educating patients about heart failure in community hospitals: it is possible...]. / Education des patients concernant l'insuffisance cardiaque en centre hospitalier général: c'est possible....

Prognosis for heart failure is linked to patient's compliance. Compliance is also dependent from patient education about his disease and treatment. Therapeutic education could be done in a community hospital but needs a lot of time. However, therapeutic education for heart failure patients becomes more and more essential in clinical practice and improves patient knowledge and implication and hospitalization duration.

Fine-Particle ethylcellulose as a tablet binder in direct compression, immediate-release tablets.

Ethylcellullose has traditionally been used in tablets as a binder in an alcohol solution form. In the present study, fine-particle ethylcellulose (FPEC) was used as a binder to manufacture immediate-release tablets by the direct compression technique. The binding potential of FPEC is compared to that of commercially available coarse-particle ethylcellulose at the same viscosity grade and to that of hydrophilic binders. The compression force setting was kept constant for all batches. The concentration of the binder was varied from 5% to 25%. Acetaminophen was used as a model drug because capping is a problem frequently observed during high-speed compaction and further processing of acetaminophen tablets. In this study, there would be an increase in the contact area with FPEC and hence greater bond formation. This greater bond formation should be able to reduce the problem of capping in tablets containing highly elastic materials such as acetaminophen. Tablets were evaluated based on the following tests: weight variation, extent of capping, hardness, friability, disintegration, and dissolution. Based on the results of these tests, FPEC proved to be an effective binder for directly compressed acetaminophen tablets. The 10% and 15% formulations of FPEC passed all the tests and also produced the hardest tablets.

In vitro degradation of chitosan by a commercial enzyme preparation: effect of molecular weight and degree of deacetylation.

A commercially available almond emulsin beta-glucosidase preparation has been reported to have chitobiose activity, and can hydrolyze chitin substrates due to a chitinase present in the enzyme preparation. This beta-glucosidase preparation was used to investigate hydrolytic activity on five chitosan samples with different molecular weight and degree of deacetylation. The degree of deacetylation and molecular weight of the chitosan samples were determined using a circular dichroism and a viscometric method, respectively. The hydrolytic activity of this beta-glucosidase preparation on chitosan was monitored viscometrically as the most convenient means of screening. Solutions of chitosan in pH 5.0 acetate buffer were prepared using the different viscosity grades of chitosan. The specific viscosity, measured after addition of beta-glucosidase to the above solutions, decreased dramatically over time in comparison to that of the respective control mixture without enzyme. Eadie-Hofstee plots established that hydrolysis of chitosan by this enzyme preparation obeyed Michaelis-Menten kinetics. Apparent Michaelis-Menten parameters and initial degradation rates were calculated and compared to determine the influences of the degree of deacetylation and molecular weight on the hydrolysis. The results show that higher molecular weight and higher degree of deacetylation chitosans possessed a lower affinity for the enzyme and a slower degradation rate. Faster degradation rates, then, are expected with lower molecular weight and low degree of deacetylation chitosans. Hydrolysis of these chitosan samples confirms the existence of a chitinase in the almond emulsin beta-glucosidase preparation, and further studies are warranted.

Evaluation of quantitative structure property relationships necessary for enantioresolution with lambda- and sulfobutylether lambda-carrageenan in capillary electrophoresis.

Lambda-carrageenan, a linear, high molecular weight sulfated polysaccharide, was successfully employed in both its native and sulfobutyl derivatized form as a chiral selector in capillary electrophoresis for the separation of enantiomers of basic pharmaceutical compounds. In order to characterize the chiral selectivity properties of this chiral selector, various structurally related racemic compounds were analyzed for enantiomeric interactions using capillary electrophoresis. The results of these studies were then rationalized and analyzed utilizing a general quantitative structure-property relationship (QSPR) evaluation in order to predict critical analyte structural requirements for successful enantiomeric separation. Important structural components of the analytes were found to include the aromatic content, the type of substitution on the aromatic ring, presence of a primary or secondary protonated amine, and an overall positive charge to the molecule.

Optimization of lambda-carrageenan as a chiral selector in capillary electrophoresis separations.

Lambda-carrageenan, a linear high molecular weight sulfated polysaccharide, was employed as a chiral selector in capillary electrophoresis for the separation of enantiomers of weakly basic pharmaceutical compounds. In order to improve the utility of the chiral selector, the purity and concentration of the lambda-carrageenan and other important capillary electrophoresis method parameters were investigated. The results indicated that the purity and concentration of the lambda-carrageenan, ionic strength of the buffer, and temperature were critical to successful enantioseparation. These new method conditions were then applied to previously investigated beta-blockers (such as propranolol HCl and pindolol) and racemic tryptophan derivatives. These studies were successful in identifying important method conditions for the improved enantioselectivity with lambda-carrageenan.

Formulation and process considerations for beads containing Carbopol 974P, NF resin made by extrusion-spheronization.

Preliminary studies revealed that Carbopol 974P, NF resin could be incorporated into beads manufactured by extrusion and spheronization, and can slow the release of a highly water soluble drug if calcium chloride was included in the granulating fluid to reduce the tack of the wetted polymer. In this study, the same approach was used to produce high quality chlorpheniramine maleate beads with a prolonged release duration. Because of the complex nature of the extrusion and spheronization process and the various components in the bead formulations, a statistically sound factorial experiment was considered for this study. A one-half fraction of a two level factorial design with three center points was employed to estimate the effects of simultaneously modifying multiple process and formulation variables, including the Carbopol concentration, calcium chloride concentration, water content, and the spheronization speed and time. Product yield, average bead roundness, and the drug release profile were selected as responses. Increasing the Carbopol content across the experimental range resulted in a significant (P<0.05) reduction in the percentage drug released at 25, 40, and 60 min. Results suggest that combining the conditions of high Carbopol, high water, and low calcium chloride levels with low spheronization speeds at long spheronization times produce the highest quality bead with the longest drug release duration.

The effect of the aqueous solubility of xanthine derivatives on the release mechanism from ethylcellulose matrix tablets.

Release data from ethylcellulose (EC) matrix tablets was analyzed to determine which release equation provides the best fit to the data and to observe the effect of drug solubility on the release mechanism(s). Tablets were prepared by direct compression of drug, EC, and lubricant in an appropriate mass ratio to achieve a high and a low drug loading. Theophylline, caffeine, and dyphylline were selected as non-electrolyte xanthine derivatives with solubilities from 8.3 to 330 mg/ml at 25 degrees C. Drug release studies were conducted in 37 degrees C water with UV detection at 272 nm. Several equations to characterize release mechanisms were tested with respect to the release data. Drug diffusion, polymer relaxation, and tablet erosion were the mechanisms considered. Parameters were generated and ANOVA data presented by WinNonlin Pro(R) software. The Akaike Information Criterion was also considered to ascertain the best fit equation. At high drug loading, drug was released by a diffusion mechanism with a rate constant that increased with an increase in aqueous solubility. At low drug loading, polymer relaxation also became a component of the release mechanism. However, its contribution to drug release was less pronounced as solubility decreases, becoming negligible in the case of theophylline.

The antimicrobial activity of vancomycin in the presence and absence of sodium carboxymethyl starch.

The purpose of this work was to determine any effects the presence of sodium carboxymethyl starch may have on the antimicrobial activity of vancomycin given a previously described interaction between vancomycin and sodium carboxymethyl starch. In particular, the in-vitro activity of vancomycin against two clinically relevant bacteria, Staphylococcus aureus and Enterococcus faecalis, was studied in the presence of varying concentrations of sodium carboxymethyl starch. From two independent studies conducted using an agar dilution method, it appeared that the binding of vancomycin to sodium carboxymethyl starch had no effect on the in-vitro antimicrobial activity of vancomycin. The minimum inhibitory concentration of vancomycin against S. aureus in the presence of as much as 1 mg mL(-1) sodium carboxymethyl starch was similar to that of the control where no sodium carboxymethyl starch was added (1-4 microg mL(-1) vs 1-2 microg mL(-1), respectively). Likewise, the minimum inhibitory concentration of vancomycin against E. faecalis in the presence of 1 mg mL(-1) sodium carboxymethyl starch was also similar to that of the control where no sodium carboxymethyl starch was added (1-4 microg mL(-1) vs 1-4 microg mL(-1), respectively). However, there may be factors in the in-vitro method, such as high ionic strength, that could disrupt the interaction between vancomycin and sodium carboxymethyl starch. Therefore, the possibility of diminished vancomycin activity in-vivo cannot be ruled out. A small percentage (8-10%) of vancomycin was determined to be bound to sodium carboxymethyl starch in broth media. Given these results, the impact of sodium carboxymethyl starch on the in-vitro antimicrobial activity of vancomycin is expected to be minimal. Binding studies could not be conducted with gelled agar due to its semi-solid state.

Differential molar heat capacities to test ideal solubility estimations.

PURPOSE: Calculation of the ideal solubility of a crystalline solute in a liquid solvent requires knowledge of the difference in the molar heat capacity at constant pressure of the solid and the supercooled liquid forms of the solute, delta Cp. Since this parameter is not usually known, two assumptions have been used to simplify the expression. The first is that delta Cp can be considered equal to zero; the alternate assumption is that the molar entropy of fusion, delta Sf, is an estimate of delta Cp. Reports claiming the superiority of one assumption over the other, on the basis of calculations done using experimentally determined parameters, have appeared in the literature. The validity of the assumptions in predicting the ideal solubility of five structurally unrelated compounds of pharmaceutical interest, with melting points in the range 420 to 470 K, was evaluated in this study. METHODS: Solid and liquid heat capacities of each compound near its melting point were determined using differential scanning calorimetry. Linear equations describing the heat capacities were extrapolated to the melting point to generate the differential molar heat capacity. RESULTS: Linear data were obtained for both crystal and liquid heat capacities of sample and test compounds. For each sample, ideal solubility at 298 K was calculated and compared to the two estimates generated using literature equations based on the differential molar heat capacity assumptions. CONCLUSIONS: For the compounds studied, delta Cp was not negligible and was closer to delta Sf than to zero. However, neither of the two assumptions was valid for accurately estimating the ideal solubility as given by the full equation.

Drug solubility effects on predicting optimum conditions for extrusion and spheronization of pellets.

This paper explores the utility of aqueous solubility of structurally similar drugs in predicting optimum conditions for extrusion and spheronization of pellets using response surface methodology. Pharmacologically active xanthine derivatives exhibiting widely varying aqueous solubility were used to determine optimum conditions for pelletization. The amount of water added to the formulation, wet mixing time, and spheronizing time were explored in a series of central composite experimental designs to exhaustively explore and mathematically model the response surfaces for each drug. Using a marketed microcrystalline cellulose excipient, optimum extrusion and spheronization conditions for less soluble drugs required more water, a longer wet mixing time, and prolonged spheronizing times. Results were similar when a new microcrystalline cellulose was substituted, except that more water was required. When comparing results for different drugs, a strong linear relationship was observed between the aqueous solubility of the drug and the water content required for optimum pellet production. The water content range over which quality pellets could be produced was much broader for poorly soluble drugs. Aqueous solubility of the active component appears to be a good predictor for the water requirements for optimum extrusion and spheronization of pellets for pharmaceutical applications.

Lambda-carrageenan: a novel chiral selector for capillary electrophoresis.

Lambda-carrageenan, a linear high molecular weight sulfated polysaccharide, has been employed as a chiral selector in capillary electrophoresis for the separation of enantiomers of weakly basic pharmaceutical compounds. The racemic compounds that were enantioresolved included propranolol, pindolol, tryptophanol, laudanosine and laudanosoline. In addition, the diastereomeric pair of cinchonine and cinchonidine were also resolved. Method conditions such as buffer pH, electrolyte concentration, column temperature, and chiral selector concentration were found to be important for improvement of enantioselectivity.

A comparison of two quality assessment methods for emulsions.

A common method of assessing the quality of emulsions is to evaluate the size distribution of the globules of the internal phase. The primary aim of this work is to compare the sensitivity of this test to an alternative method. The sizes of the globules of two emulsions, an oral emulsion and a total parenteral nutrition (TPN) emulsion, were determined using a light microscope. Globule size analyses were performed upon preparation and during storage of the emulsions. Using a computer program specially developed for this study, the recorded diameters were placed into size groups and the volumes of each of the measured globules was determined. For each size group, the total volume of all the globules within the group and the volume percentage of the oil phase represented by the group were calculated. The volume distribution of the internal phase across the size groups was found to predict emulsion instability better than the globule number distribution and thus is a better determinant of emulsion quality. This technique may have general application in the evaluation of TPN emulsions and other spheres, such as liposomes.

An enzymatic assay for the MAO-B inhibitor selegiline in plasma.

A sensitive fluorimetric assay based on inhibition of rat brain monoamine oxidase-B (MAO-B) in vitro has been described. The procedure measures the inhibition of MAO activity produced by the addition of selegiline extracted from human plasma. This method uses the substrate kynuramine which is converted by MAO to the product 4-hydroxyquinoline which fluoresces in alkaline solution. Human plasma (500 microliters) containing different concentrations of selegiline was deproteinized and extracted with ethyl acetate-butyl chloride. After reconstitution with 200 microliters phosphate buffer, 50 microliters of rat brain homogenate was added to study the MAO-B inhibition. Selegiline metabolites, amphetamine and methamphetamine (50 ng ml-1), and desmethylselegiline (20 ng ml-1), showed no inhibitory effect on MAO-B inhibition. Selegiline concentrations as low as 0.25 ng ml-1 can be detected. The standard curve was linear from 125 pg (0.25 ng ml-1) to 4000 pg (8.0 ng ml-1) in the incubation tube. This method should be helpful to determine pharmacokinetic parameters of selegiline after i.v. or oral dosing.

Oestrone loaded poly(l-lactic acid) microspheres: preparation, evaluation and in vitro release kinetics.

Poly(l-lactic acid) microspheres containing oestrone were prepared by the solvent evaporation method using methylene chloride as the casting solvent and poly(vinyl alcohol) as the emulsifier. Non-agglomerated microspheres with average diameters of 125-160 microns, containing 3-18 per cent oestrone were prepared successfully using a stirring rate of 650 rpm and a poly(vinyl alcohol) concentration as low as 0.15%. Drug loading decreased with an increase in the relative amounts of methylene chloride or emulsifier. Microspheres with 9 per cent loading released approximately 50 per cent of the drug in the first 12 h and the remainder at a much slower rate over several days. Initial examination revealed that the kinetic data followed both a first-order release pattern and the Higuchi matrix model. Differential rate treatment confirmed the Higuchi matrix model and the release mechanism was determined to be diffusion-controlled.

Solid and liquid heat capacities of n-alkyl para-aminobenzoates near the melting point.

The expression that relates the ideal mole fraction solubility of a crystalline compound to physicochemical properties of the compound includes a term involving the difference in the heat capacities of the solid and liquid forms of the solute, delta Cp. There are two alternate conventions which are employed to eliminate this term. The first assumes that the term involving delta Cp, or delta Cp itself, is zero. The alternate assumption assigns the value of the entropy of fusion to the differential heat capacity. The relative validity of these two assumptions was evaluated using the straight-chain alkyl para-aminobenzoates as test compounds. The heat capacities of the solid and liquid forms of each of the para-aminobenzoates, near the respective melting point, were determined by differential scanning calorimetry. The data lead one to conclude that the assumption that the differential heat capacity is not usually negligible and is better approximated by the entropy of fusion.