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Biomedical subjects

F Podczeck

Publications and source records attributed to F Podczeck.

49 records · Page 3Linked to original sources
PubMed1999

Determination of the gastric emptying of solid dosage forms using gamma-scintigraphy: a problem of image timing and mathematical analysis.

This work was designed to identify the maximum time interval of image acquisition by gamma-scintigraphy for monitoring the emptying of a dosage form such as a tablet. Appropriate statistical parameters to describe this process were sought, including a statistical procedure for group comparisons of such data. Gamma-scintigraphy was employed in seven healthy male volunteers, who swallowed a light and a dense tablet, each 12 mm in diameter, formulated to contain different isotopes to allow identification. Images were taken sequentially at 30-s intervals to provide images of each tablet in 1-min spacing until emptying of both tablets was reported. In selecting images, it was also possible to simulate image acquisition intervals of 2, 3, 5, 10, 15, 20 and 30 min. The values derived are discrete random variables. The maximum time interval between image acquisitions that permitted reliable results to be obtained was found to be 3 min for light and 2 min for dense tablets. Consideration of the emptying of a tablet as a Bernoulli random event provided a suitable statistical approach to the analysis of such data, giving a median and an interquartile range. While the commonly applied method, which is based on parametric procedures deriving arithmetic means and standard deviations, failed to detect a difference in the emptying times of the two types of tablets, the use of non-parametric statistics (Wilcoxon test) provided a clear distinction between them in this respect. The assessment of gastric emptying by gamma-scintigraphy studies can be improved by using short image intervals and application of appropriate statistical analysis.

Adult↗
PubMed1999

The influence of water content and drug solubility on the formulation of pellets by extrusion and spheronisation.

The influence of drug solubility in the range 14.3-1000 gl-1 on the formation of pellets by extrusion and spheronisation has been investigated by evaluating the performance of a series of model drugs mixed with an equal part by weight of microcrystalline cellulose. The optimum formulation in terms of pellet roundness and the maximum quantity within a limited size range was established by preparing samples with a range of water levels. The range of water levels over which pellets could be formed was found to be dependent on the model drug and its particle size. In general the force necessary to extrude the wet mass through the ram extruder was found to decrease as the quantity of water added increased. The optimum water level required to form the best quality pellets was found to decrease as a linear function of the natural logarithm of the water solubility of the drug. If allowance is made for the loss of solid by dissolution of the drug, there is an increase in the apparent water content necessary to form good spheres above a critical solubility between 350 and 400 gl-1.

Cellulose↗
PubMed1998

The effect of an increase in chain length on the mechanical properties of polyethylene glycols.

The mechanical properties of different molecular weights of polyethylene glycol (PEG) have been determined by formation of compacted tablets and beams, which were subjected to diametral compression and 3-point bending, respectively. From diametral compression, the tensile strength for the different grades of PEG was determined. Flat beams made from powder by compaction were used to determine Young's modulus of elasticity. Beams into which a notch had been introduced after formation allowed the fracture mechanical parameters of critical stress intensity factor, K(IC), and fracture toughness, R, to be determined. Evaluation of these parameters as a function of compact porosity allowed extrapolation to values at zero porosity, providing an estimate of the material properties. The increase in chain length of the PEG was found to have a non-linear effect on tensile strength and Young's modulus. The ductility of the polymer increased proportionally to the increase in chain length, reflected by the linear relationship between K(IC) and the molecular weight. Young's modulus and critical stress intensity factor allowed the estimation of the strain energy release rate, G(IC), which is the driving force in crack propagation. Consequently, the tensile strength at zero porosity was found to be predictable from the values of G(IC) and the molecular weight of the different grades of PEG.

Chemistry, Pharmaceutical↗
PubMed1998

Compaction of, and drug release from, coated drug pellets mixed with other pellets.

Tablets have been prepared at known compaction force from three types of pellets in different proportions: (1) pellets containing 80% theophylline as a model drug coated with different thicknesses of a polymer film coat, (2) pellets containing glyceryl monostearate as a deformable material, and (3) pellets containing a disintegrant. The breaking load, friability, disintegration and drug release properties were evaluated, the latter as a mean dissolution time (MDT) and its variance (VDT). The mechanism of dissolution was assessed from the value of the relative dispersion (RD) of the mean dissolution time. The possible relationship between the properties of the pellets and those of the tablets was evaluated by canonical analysis followed by multiple regression analysis. It was found that only about 51% of the tablet properties could be predicted from the properties of the pellets. The quantitative relationship between pellet properties and tablet properties was found to vary in type and level of quality. Reduction of breaking load, friability and disintegration was less predictable than that of dissolution represented as the MDT. The values of RD for the different preparations clearly identified those preparations where the film coat still retained control of the dissolution process. Such formulations contained at least 40% of soft pellets and coated pellets with at least a weight gain of 8%.

Chemistry, Pharmaceutical↗
PubMed1998

The characterization of the mechanical strength of chewable tablets.

The purpose of this research was to identify possible test procedures for the evaluation of the strength of chewable tablets with respect to prevention of damage to teeth or mandibular joints when tablets are consumed. Diametral compression and flexure tests were employed to evaluate the strength of commercial samples from five manufacturers of chewable vitamin C tablets. Weibull analysis was used to assess the brittleness of these tablets. The tablets had a lower tensile strength value when determined by the diametral compression test compared to the flexure test ratio which ranged from 0.27 to 0.4. The value for the Weibull modulus ranged from 5 to 16, indicating an appreciable degree of brittleness of the samples. Relating the values for the mechanical strength to suggested practical values for the prevention of damage to the teeth or the mandibular joints indicated that most tablets exceeded these values. The flexure test reflects the practical situation closest, and a limiting tensile strength value of 2 MPa should not be exceeded for chewable tablets. The tablet batches tested were also characterized by a large batch-to-batch variability, suggesting uncontrolled manufacturing procedures. Commercially distributed chewable vitamin C tablets could provide a possible health hazard to teeth and mandibular joints. This hazard could be limited by a mechanical strength test specification.

Mastication↗
PubMed1997

Influence of Relative Humidity of Storage Air on the Adhesion and Autoadhesion of Micronized Particles to Particulate and Compacted Powder Surfaces

The influence of the relative humidity of storage air on the median adhesion force at the interface of lactose monohydrate and salmeterol xinafoate has been investigated by the centrifuge technique using particle-on-particle and particle-on-surface experiments. The relative humidity of storage air can strongly affect the median adhesion force. Condensed moisture was found to result in strong irreversible solid bridge bonds or in weak solid bridge bonds that are of comparable strength to Lifshitz-van der Waals forces obtained under conditions of low relative humidity up to 35%. The effect was dependent on the structure of the substrate surface, the solubility of the particles adhered, and the solubility of the surface material. The use of different substrate surfaces such as particles and compacted powder disks of identical materials led to different results. Hence, if the influence of relative humidity of storage air on the adhesion between particles in, for example, an interactive mixture is to be predicted, the adhesion measurements have to be performed using particle-on-particle adhesion force measurements. Relative humidity of the air greater than 75% results in irreversible, strong forces acting at the interface of the particles. Below this humidity level, capillary forces can be removed by storing the mixtures at a very low relative humidity of about 5% for at least 72 h.

Journal Article↗
PubMed1997

The development of a cascade impactor simulator based on adhesion force measurements to aid the development of dry powder inhalations.

Adhesion and friction forces are the main physical factors determining the re-suspension of a micronized drug from carrier particles during inhalation. Hence, it appears useful to link adhesion and friction force measurements to the in vitro testing of dry powder inhalations, namely the assessment of the mass median aerodynamic diameter (MMAD) using an eight-stage Andersen cascade impactor. Interactive mixtures of micronized Salmeterol Xinafoate adhered to irrespirable lactose monohydrate carrier particles were used as model dosage forms. The adhesion force between the drug and carrier particles was assessed using a centrifuge technique, and the MMAD was determined under standardized working conditions using the Andersen-Cascade impactor (Mark II). A cascade impactor simulator (CIS), which is a computer program containing a re-suspension model to assess the amount of drug detached from the carrier particles during inhalation, was developed and validated using the experimental data. It could be shown, that the CIS provided a good estimate of the loss of drug due to adhesion to the carrier particles and the loss of drug on the cascade impactor walls. Small deviations between the theoretical and experimental mass median aerodynamic particle diameters however were found. These deviations were shown to be mainly due to the experimental error introduced by the cascade impactor, and that the error due to the experimental adhesion measurements is negligibly small. Hence, the CIS developed could be a useful tool in early development stages of dry powder inhalations to predict the in vitro aerodynamic performance of drug particles.

Adhesiveness↗
PubMed1996

Evaluation, by a statistically designed experiment, of an experimental grade of microcrystalline cellulose, Avicel 955, as a technology to aid the production of pellets with high drug loading.

A statistically designed experiment has been undertaken to evaluate an experimental grade of microcrystalline cellulose (Avicel 955) as a technology to aid the production of pellets by extrusion spheronization of formulations with high drug load. An attempt has been made to relate the properties of the drugs to the ability to produce spherical pellets which have a narrow size distribution and are round, as assessed by a 2-dimensional shape factor by the process of extrusion/spheronization. Twenty drugs were tested at a level of 80%, and in all cases pellets could be produced. In some cases in terms of either size distribution or shape they were not of the highest quality. Nevertheless, a best level of water was identified for each drug. Principal component analysis did allow structuring of the data characterizing the process and the pellets, identifying a relationship between the water content and the steady state extrusion force as one component with the median pellet size and its interquartile range as the other. When multivariate analysis was used with the whole data set, it was not possible to relate the drug properties of pKa, freezing point depression, or solubility to the water content, steady state extrusion force, median pellet diameter, its interquartile range, and its shape satisfactorily. Thus other properties of the drug must be involved in the extrusion/spheronization process. Prediction of the best water content to use in a formulation was possible for 50% of the formulations by using a nonlinear model to relate the above drug properties to the water content.

Cellulose↗
PubMed1996

Investigations into the relationship between drug properties, filling, and the release of drugs from hard gelatin capsules using multivariate statistical analysis.

PURPOSE: The aim of the present work is to identify complex relationships between formulation variables and dosage form properties to aid the development of hard gelatin capsules. METHODS: Multivariate statistical analysis was employed based on a statistical design, which considered drug solubility, particle size and concentration, type and concentration of filler and disintegrant, and concentration of standard lubricant and glidant as the main influence factors. Both the filling properties of the formulations and the disintegration/dissolution properties of the capsule content were studied. RESULTS: From the two multivariate statistical methods used, nonparametric canonical analysis proved to be the superior method to deal with the complex information included in the data. While the filling performance of the formulation could clearly be attributed to the formulation variables such as drug particle size, type of filler, concentration of drug and glidant, the disintegration of the capsules and the dissolution of the drugs was not strongly related to the formulation variables chosen. In this respect as a trend, the drug solubility, and the type of disintegrant and filler appear to be more important factors. CONCLUSIONS: Based on an appropriate number of experiments, organised in a statistical design, nonparametric canonical analysis can be used to identify relationships in a set of data that is grouped in influence and response variables to aid the development of a dosage form.

Capsules↗
PubMed1995

Development of an ultracentrifuge technique to determine the adhesion and friction properties between particles and surfaces.

The extension of a centrifuge technique to measure adhesion and friction forces to an ultracentrifuge has been described. The equipment and procedure provide many experimental possibilities of which the adhesion of single particles to flat compacted powder surfaces has been used to measure the adhesion and friction force of starch microspheres to microcrystalline cellulose. The equipment used allows the positioning of the adhesion samples in the rotor in such a way that any angle between the centrifugal force vector and the flat sample surface can be obtained, and hence both adhesion and friction forces can be measured. The adhesion strength between starch microspheres and microcrystalline cellulose could initially be increased by applying a higher press-on force. However, a maximum plastic deformation and hence maximum contact area between the spheres and the surfaces was eventually reached, and any further application of press-on force appeared to lead only to more elastic deformation and hence not to an increase in adhesion strength. The friction between the starch microspheres and the compacted microcrystalline cellulose surfaces at a maximum deformation of the spheres is still very low, so that starch microspheres could be used as excipient in mixtures including microcrystalline cellulose for example in tabletting.

Adhesiveness↗
PubMed1995

The description of the gastrointestinal transit of pellets assessed by gamma scintigraphy using statistical moments.

The gastrointestinal transit of multiple units (e.g., pellets), as determined by gamma scintigraphy, has been characterized by the application of statistical moments. Stomach emptying profiles can be described comprehensively by Mean Gastric Residence Time (MGRT) and Variance of Gastric Residence Time (VGRT) and caecum arrival data by Mean Caecum Arrival Time (MCAT) and Variance of Caecal Arrival Time (VCAT). This maximizes the data available, which is not the case when only described as 50% values. The statistical moments provide different information about the data observed compared to the classical descriptors, as there was only limited correlation between these two sets of parameters. Statistical moments therefore provide an important quantification of the process studied, and they can be used in any statistical test, where it is required to compare different experimental conditions.

Data Collection↗
PubMed1994

A shape factor to characterize the quality of spheroids.

A shape factor eR has been devised to describe how the form of spherical particles approaches that of a true spheroid, based on a two-dimensional image analysis. Both the deviation of shape from a circle towards an ellipse and surface irregularities influence the value of eR. Using a set of model figures such as squares, triangles, diamonds and stars, it could be shown that eR clearly differentiates between different polygonally symmetric figures, even in the case where common shape descriptors such as the aspect ratio provide equal values. The value of eR is 1.0 in the case of a perfect spheroid, while ellipticity and surface roughness lead to a significant change in the value.

Drug Design↗