Use of a capillary rheometer to evaluate the rheological properties of microcrystalline cellulose and silicified microcrystalline cellulose wet masses

The influence of microcrystalline cellulose (MCC) type and water content on the rheological properties of the wet powder masses were studied using two different MCC grades (Avicel and Emcocel) and silicified microcrystalline cellulose (SMCC, Prosolv). A ram extruder was used as a capillary rheometer and unique flow curves for each cellulose grade and moisture content were derived. In addition, the elastic parameters of recoverable shear and compliance were determined. From different flow curve models evaluated, it was not possible to obtain clear evidence, which model best described the rheological properties of each cellulose grade at each water level. Furthermore, the residuals were shear rate dependent, which indicates that the models do not perfectly agree with physical properties of the wet masses. The elastic properties of wet masses increased with increasing water content and decreased with increasing shear stresses. SMCC grade proved to be more elastic than the simple MCC grades at each moisture content. Thus, the rheological properties of MCC and SMCC wet masses were different and changed with water content. Consequently, it was not possible to achieve similar rheological properties between different grades of cellulose by altering the water content of the wet mass.     

The influence of type and quantity of model drug on the extrusion/spheronization of mixtures with microcrystalline cellulose. I. Extrusion parameters

Five model drugs, (methyl, propyl and butyl paraben, 4-hydroxybenzoic acid and propyl gallate), similar in their chemical structure were mixed with microcrystalline cellulose and water in different proportions and forced through a ram extruder. The overall water movement was measured by the difference between the initial water in the formulation and the water content in the plug remaining after extrusion was completed. The differences in theoretical and practical volume occupancy of the materials inside the barrel were calculated to look for trapped air inside the barrel. The steady-state extrusion force for each formulation was recorded. All five materials demonstrated differences in behaviour during extrusion. The relationship between each of the three properties measured and both the drug-load and initial water content was examined, to establish the potential relationship that existed between the differences due to the drug models. The five drug models were divided into two sub-groups, when examining the way that they underwent extrusion. Methyl, propyl and butyl paraben formed one group while 4-hydroxybenzoic acid and propyl gallate formed the other group. Within the former group the relationship between steady-state extrusion force and the percentage of drug and water present tended to be lower than those in the latter group. For the former group these relationships were non-linear.     

The development of an instrumented tamp-filling capsule machine I: Instrumentation of a Bosch GKF 400S machine and feasibility study

The instrumentation of capsule filling machines operating by the tamp-filling principle has been described only once, using strain gauges. In the present paper the instrumentation of a Bosch GKF 400S tamp-filling machine has been described using a prototype of a pneumatic tamping head equipped with a piezoelectric force transducer. The pneumatic system replaces the conventional springs situated between tamping pins and upper part of the tamping head. Via a feedback switch valve, the air pressure inside the pneumatic chamber can be regulated. This provides a potential mechanism for feedback control of capsule fill weight during continuous capsule filling. It was found that the use of the pneumatic tamping head is limited to the control of fill weight during tamping. Major adjustments of fill weight at the set-up stage of the machine should be made by alteration of the tamping pin and powder bed height settings. The principles of capsule fill weight control by continuous monitoring of tamping forces have been established, but the transfer of the system to full industrial use requires further development of the prototype by the machine manufacturer.     

Powder and capsule filling properties of lubricated granulated cellulose powder

Granulated powdered cellulose was studied in terms of powder bulk properties and capsule filling performance on a tamp-filling machine with and without the addition of various concentrations of magnesium stearate. Carr's compressibility reached its minimum value at 0.4% magnesium stearate suggesting an improvement of powder flow compared to the unlubricated material. However, shear cell measurements and the use of a powder rheometer indicated that the addition of 0.2% magnesium stearate and more impairs powder flow and does not reduce interparticulate friction. When capsules were filled into hard gelatine capsules at a zero-compression setting, the fill weight and plug density could be predicted from Carr's compressibility index and from the maximum bulk density. The decrease in one and simultaneous increase in the other bulk property with increasing magnesium stearate concentration caused both fill weight and plug density to go through a minimum at a lubricant concentration of 0.4%. When the capsules were filled at maximum compression, however, the addition of lubricant increased the coefficient of fill weight variation significantly, and the plug density remained constant for any added concentration of magnesium stearate. These findings were in agreement with the shear cell and powder rheometer results. However, the optimum lubricant concentration in terms of ease of machine function, which was identified from tamping pressure measurements, was found to be 0.8% magnesium stearate, which was not an optimal concentration for the powder bulk properties.     

Transvenous high frequency current ablation of atrioventricular conduction in therapy refractory tachycardic atrial fibrillation

We present a case of radiofrequency ablation of the atrioventricular conduction system by means of intravenous catheter technique in a patient with drug-refractory paroxysmal atrial fibrillation. Total AV block was produced. Since the ablation and implantation of a pacemaker this female has had no recurrences. The advantages of this method compared with electrical fulguration are better control of delivered energy and reduction of complications (catheter perforation, thromboembolism). The disadvantage of radiofrequency ablation is the difficulty in positioning the catheter so as to give the most precise contact with the tissue, which is a very time-consuming procedure.     

Acute oral poisoning with lindane-solvent mixtures

Six cases of oral intoxication with lindane-solvent mixtures are reviewed. The ingested doses of lindane (mean dosage 120 mg/kg +/- 86 mg/kg) and benzene (mean dosage 366 mg/kg +/- 93 mg/kg) exceeded the toxic level. Symptoms (vomiting, dizziness and hyperreflexia) occurred within 30 min and all patients had epileptiform seizures. Two patients suffered from pulmonary edema and one of them had a severe rhabdomyolysis. Diazepam was sufficient to control convulsions in five cases. Gastric lavage was performed in five patients and activated charcoal, liquid paraffin with saline cathartic, and cholestyramine were used as adsorbents. Recovery was complete in all patients.     

Diagnostic value of electrocardiographic variables to predict the presence of ventricular late potentials

To test the hypothesis that the presence of ventricular late potentials in the highly amplified, averaged and filtered surface electrocardiogram (ECG) can be predicted from the conventional surface ECG, 211 patients with and without previously documented sustained ventricular tachycardia outside the acute phase of myocardial infarction were studied. The presence of left ventricular akinesia or aneurysm was significantly correlated with the ECG score (based on Q wave duration, R wave duration and amplitude ratio). The mean ECG score in patients without ventricular tachycardia was 3.4 +/- 3.5 points compared with 5.5 +/- 3.9 points (p less than 0.001) in patients with ventricular tachycardia. The presence of late potentials was positively correlated with the ECG score in the whole cohort of patients. This was also the case in the subgroup of patients without a history of sustained ventricular tachycardia. In contrast, in patients with ventricular tachycardia, the presence of late potentials was independent of their ECG score. Using linear discriminant function analyses to predict the presence of late potentials, a history of ventricular tachycardia alone and the ECG score alone had a high predictive power (high standardized coefficients). If combinations of variables were analyzed including estimates of left ventricular function (presence of aneurysm or akinesia; ejection fraction), the ECG score and a history of ventricular tachycardia still ranked highest. The influence of ejection fraction if used in combination with other variables for the prediction of late potentials was relatively small (standardized coefficient of 0.4). In conclusion, the surface ECG can be used in patients previously free of sustained ventricular tachycardia to predict the presence of ventricular late potentials.(ABSTRACT TRUNCATED AT 250 WORDS)     

Measuring the water retention capacities (MRC) of different microcrystalline cellulose grades.

The ability of various types of microcrystalline cellulose (MCC) to hold water when subjected to an applied force has been assessed by a centrifuge technique. By considering the final percent of water retained after a standard centrifugation, as a function of the initial water content, a moisture retention capacity (MRC) can be determined. Statistical analysis of the results identified that it was possible to divide the nine samples of MCC into six sub-sets in terms of final moisture content retained. Those types which contained added polymer had by far the highest water level remaining. In terms of the MRC value, statistical analysis again sub-divided the celluloses into six sub-sets, although different from those for the final water content. Again those types containing added polymer gave much higher MRC values. As experiments were carried out with initial water/MCC ratios of different levels, statistical analysis of the influence of initial water content on the MRC values was undertaken with each type of MCC. The results showed a varying dependence on initial water level with the different types of cellulose. To provide a value of MRC which characterised the cellulose, the maximum value of MRC at the lowest initial water level was identified. Samples of MCC with low values of MRC have been shown previously to require less water for processing by extrusion/spheronization, while celluloses with a high MRC value appear better for the limitation of water movement during the process of extrusion/spheronization. The water retention must, however, also be considered in association with the rheological properties of the wet powder mass. Thus, while the Avicel RC591 had the highest MRC value, its rheological properties are so that the production of pellets with such a type can be less effective than with other types of MCC.