Biomedical subjects

Jouko Yliruusi

Publications and source records attributed to Jouko Yliruusi.

At least 37 records · Page 2Linked to original sources

PubMed2004

The characterization of fluidization behavior using a novel multichamber microscale fluid bed.

In the preformulation stage, there is a special need to determine the process behavior of materials with smaller amounts of samples. The purpose of this study was to assemble a novel automated multichamber microscale fluid bed module with a process air control unit for the characterization of fluidization behavior in variable conditions. The results were evaluated on the basis of two common computational methods, the minimum fluidization velocity, and the Geldart classification. The materials studied were different particle sizes of glass beads, microcrystalline cellulose, and silicified microcrystalline cellulose. During processing, the different characteristic fluidization phases (e.g., plugging, bubbling, slugging, and turbulent fluidization) of the materials were observed by the pressure difference over the bed. When the moisture content of the process air was increased, the amount of free charge carriers increased and the fine glass beads fluidized on the limited range of velocity. The silicification was demonstrated to improve the fluidization behavior with two different particle sizes of cellulose powders. Due to the interparticle (e.g., electrostatic) forces of the fine solids, the utilization of the computational predictions was restricted. The presented setup is a novel approach for studying process behavior with only a few grams of materials.

Cellulose↗

PubMed2004

Comparison of torque measurements and near-infrared spectroscopy in characterization of a wet granulation process.

The purpose of this study was to compare impeller torque measurements and near-infrared (NIR) spectroscopy in the characterization of the water addition phase of a wet granulation process. Additionally, the effect of hydrate formation during granulation on the impeller torque was investigated. Anhydrous theophylline, alpha-lactose monohydrate, and microcrystalline cellulose (MCC) were used as materials for the study. The materials and mixtures of them were granulated using purified water in a small-scale high-shear mixer. The impeller torque was registered and NIR spectra of wet samples were recorded at-line. The torque and the NIR baseline-corrected water absorbances increased with increasing water content. A plateau in the NIR baseline-corrected water absorbances was observed for wet masses containing MCC. This was at the region of optimal water amount for granulation according to the torque results. In the case of anhydrous theophylline, the slope of baseline-corrected water absorbance values increased at the same water amount as the impeller torque started to increase. The hydrate formation of theophylline during granulation was observed as a slight decrease in the impeller torque. In addition, the hydrate formation during granulation affected the granulation liquid requirement. The liquid requirement was different for monohydrate formed during granulation compared to one formed in high relative humidity before the granulation. The results suggest that NIR spectroscopy may be applicable to process monitoring of wet granulation, also in cases where monitoring of impeller torque is difficult to apply.

Spectroscopy, Near-Infrared↗

PubMed2004

Physical stability and moisture sorption of aqueous chitosan-amylose starch films plasticized with polyols.

The short-term stability and the water sorption of films prepared from binary mixtures of chitosan and native amylose maize starch (Hylon VII) were evaluated using free films. The aqueous polymer solutions of the free films contained 2% (w/w) film formers, glycerol, or erythritol as a plasticizer, as well as acetic acid (1%) and purified water. Characterization of the present fresh and conditioned film formers and free films was done using X-ray diffraction analysis, determination of moisture sorption isotherms, and near infrared spectroscopy. The results indicated that clear changes in the crystallinity of the films are evident within a 3-month period of storage, and the changes in the solid state are dependent on the plasticizer and storage conditions. When stored at ambient conditions for 3 months, the aqueous chitosan-amylose starch films plasticized with erythritol exhibited a partly crystalline structure. This was as a result of sugar recrystallisation due to the high hydrogen bonding. The respective films plasticized with glycerol and stored at 25 degrees C/60% relative humidity (RH) or at 40 degrees C/75% RH remained flexible and amorphous for at least 3 months. The water sorption of the free films greatly increased as a function of storage time at 75 and 95% RH. The second derivative spectra of starting material and free films were capable of distinguishing the internal water from the free water after storage at different relative humidities. Free water resulted in a separate band at a lower wavelength (1903 nm) in comparison to the structured absorbed water band at 1920 nm, in the case of films the free water resulted in a band around 1900 nm.

Amylose↗

PubMed2004

Role of excipients in hydrate formation kinetics of theophylline in wet masses studied by near-infrared spectroscopy.

Hydrate formation is a phase transition, which can occur during wet granulation. This kind of processing-induced transformation (PIT) can influence the quality of a finished product. The aim of the study was to investigate the effect of excipients on the kinetics of hydrate formation in wet masses. Anhydrous theophylline was chosen as the hydrate-forming model drug compound and two excipients, silicified microcrystalline cellulose (SMCC) and alpha-lactose monohydrate, with different water absorbing properties, were used in formulation. An early stage of wet massing was studied with anhydrous theophylline and its 1:1 (w/w) mixtures with alpha-lactose monohydrate and SMCC with 0.1g/g of purified water. The changes in the state of water were monitored using near-infrared spectroscopy, and the conversion of the crystal structure was verified using X-ray powder diffraction (XRPD). SMCC decreased the hydrate formation rate by absorbing water, but did not inhibit it. The results suggest that alpha-lactose monohydrate slightly increased the hydrate formation rate in comparison with a mass comprising only anhydrous theophylline.

Bronchodilator Agents↗

PubMed2003

A new method to predict flowability using a microscale fluid bed.

The purpose of this research was to develop a new method to predict the flow behavior of pharmaceutical powders using a multichamber microscale fluid bed. Different amounts of poorly flowing paracetamol were added to various grades of microcrystalline celluloses and silicified microcrystalline cellulose powders. Magnesium stearate was used as a lubricant. Experimental minimum fluidization velocities (u(mf)) were defined using 2 to 4 g (equal to 10 mL) of material (Video 1). The reference flowability of the powders was determined using a specific flow meter. Also, the weight variation of the compressed powders, using a single-punch press, was measured. When the amount of paracetamol in the excipients was increased, the experimental umf increased and the fluidization behavior grew worse (Video 2). Principal component analysis (PCA) established that the pressure difference over the bed as a function of fluidization velocity could be used to characterize the behavior of powders. The increase in poor fluidization behavior of the powders was in accordance with the increasing amount of paracetamol and with the increasing weight variation of the tablets. Furthermore, the angle of repose and the flow rate of silicified microcrystalline cellulose powders were predicted using a partial least squares (PLS) model. The developed method to predict flowability is a promising approach for use in the preformulation and formulation stages of new drug candidates, for example.

Acetaminophen↗

PubMed2003

Characterization of particle sizes in bulk pharmaceutical solids using digital image information.

The purpose of this study was to demonstrate a novel method of extracting relevant information from undispersed bulk powder surfaces to be used in particle size analysis. A new surface imaging approach for undispersed powders combined with multivariate modeling was used. Digital surface images of various granule batches were captured using an inventive optical setup in controlled illumination conditions. A descriptor, the gray scale difference matrix (GSDM), which describes the particle size of granular material was generated and extracted from the powder surface image information. Partial least squares (PLS) modeling was used to create a model between the GSDM and the particle size distribution of granules measured with sieving. The use of lateral illumination and the combining of information from 2 surface images strengthened the shading effects on the powder surfaces. The shading effects exposed the topography or the visual texture of the powder surfaces. This textural information was efficiently extracted using the GSDM descriptor. The goodness-of-fit (R2) for the created PLS model was 0.91 and the predicted variation (Q2) was 0.87, indicating a good model. The model covered granule sizes in the size range of approximately 20 to 2500 microm. The extracted descriptor was effectively used in particle size measurement. This study confirms that digital images taken from undispersed bulk powder surfaces contain substantial information needed for particle size distribution analysis. The use of the GSDM enabled the utilization of bulk powder surface information and provided a fast method for particle size measurement.

Chemistry, Pharmaceutical↗

PubMed2003

Prediction of physicochemical properties based on neural network modelling.

The literature describing neural network modelling to predict physicochemical properties of organic compounds from the molecular structure is reviewed from the perspective of pharmaceutical research. The standard three-layer, feed-forward neural network is the technique most frequently used, although the use of other techniques is increasing. Various approaches to describe the molecular structure have been successfully used, including molecular fragments, topological indices, and descriptors calculated by semi-empirical quantum chemical methods. Some physicochemical properties, such as octanol-water partition coefficient, water solubility, boiling point and vapour pressure, have been modelled by several research groups over the years using different approaches and structurally diverse large training sets. The prediction accuracy of most models seems to be rather close to the performance of the experimental measurements, when the accuracy is assessed with a test set from the working database. Results with independent test sets have been less satisfactory. Implications of this problem are discussed.

Chemical Phenomena↗

PubMed2003

Tablet surface characterisation by various imaging techniques.

The aim of this study was to characterise tablet surfaces using different imaging and roughness analytical techniques including optical microscopy, scanning electron microscopy (SEM), laser profilometry and atomic force microscopy (AFM). The test materials compressed were potassium chloride (KCl) and sodium chloride (NaCl). It was found that all methods used suggested that the KCl tablets were smoother than the NaCl tablets and higher compression pressure made the tablets smoother. Imaging methods like optical microscopy and SEM can give useful information about the roughness of the sample surface, but they do not provide quantitative information about surface roughness. Laser profilometry and AFM on the other hand provide quantitative roughness data from two different scales, laser profilometer from 1 mm and atomic force microscope from 90 microm scale. AFM is a powerful technique but other imaging and roughness measuring methods like SEM, optical microscopy and laser profilometry give valuable additional information.

Compressive Strength↗

PubMed2003

Determining the compression behaviour of pharmaceutical powders from the force-distance compression profile.

The force-displacement curves obtained from an eccentric tablet machine were examined in a new way. The tendency of the material for plastic deformation, fragmentation and elasticity is expressed as numerical values, which are comparable between different materials. The dependence of these numerical values on the compression pressure was modelled. The accuracy of the displacement measurement was improved by filtering out noise from the measurement data by a novel method. The plastic deformation of the material near the force maximum of the compression cycle could be seen accurately from this precise displacement data. The elastic deformation of the tablet machine was also defined very precisely from the running machine. Tablets were made with an eccentric tablet machine using fixed lower and upper punch adjustments. This ensured that the speed of the upper punch and the theoretical height of the tablets were the same for all compactions. Therefore, only the properties of the materials determined the differences in the shape of the compression curves. The test materials used were alpha-lactose monohydrate, two grades of microcrystalline cellulose, maize starch and dicalcium phosphate dihydrate. The results showed that the use of accurate displacement measurement is essential in order, to see the small variations in the shape of the force-displacement curve near the force maximum of the compression cycle, and it made it possible to dynamically calibrate the elastic deformation of the eccentric tablet machine during compression. It turned out that the numerical values obtained with the new method described the plastic, brittle and elastic properties of the tested materials satisfactorily in a wide compression pressure range.

Compressive Strength↗

PubMed2003

Effects of excipients on hydrate formation in wet masses containing theophylline.

Transformations between solid phases in dosage forms can lead to instability in drug release. Thus, it is important to understand mechanisms and kinetics of phase transformations and factors that may influence them. During wet granulation theophylline shows pseudopolymorphic changes that may alter its dissolution rate. The aim of this study was to investigate whether excipients, such as alpha-lactose monohydrate or the highly water absorbing silicified microcrystalline cellulose (SMCC) can influence the hydrate formation of theophylline. In particular, the aim was to study if SMCC offers protection against the formation of theophylline monohydrate relative to alpha-lactose monohydrate in wet masses after an overnight equilibration and the stability of final granules during controlled storage. In addition, the aim was to study the use of spectroscopic methods to identify hydrate formation in the formulations containing excipients. Off-line evaluation of materials was performed using X-ray powder diffractometry, near infrared and Raman spectroscopy. alpha-Lactose monohydrate with minimal water absorbing potential was not able to prevent but enhanced hydrate formation of theophylline. Even though SMCC is able to take large amounts of water into its internal structure, it was able to inhibit the formation of theophylline monohydrate only at low moisture contents, not at the amounts of water needed to form granules. Both the spectroscopic methods used could identify the hydrate formation even though there were excipients in the formulation.

Absorption↗

PubMed2003

Dehydration studies using a novel multichamber microscale fluid bed dryer with in-line near-infrared measurement.

The purpose of this research was to study the effect of two process parameters (temperature and moisture content) on dehydration behavior of different materials using a novel multichamber microscale fluid bed dryer with a process air control unit and in-line near-infrared (NIR) spectroscopy. The materials studied were disodium hydrogen phosphates with three different levels of hydrate water and wet theophylline granules. Measured process parameters of fluid bed drying were logged, including in-line NIR signals. Off-line analyses consisted of X-ray powder diffraction patterns, Fourier transform NIR spectra and moisture contents of studied materials. During fluid bed drying, the stepwise dehydration of materials was observed by the water content difference of inlet and outlet air, the pressure difference over the bed, and the in-line NIR spectroscopy. The off-line analysis confirmed the state of solid materials. The temperature and the moisture content of the process air were demonstrated to be significant factors for the solid-state stability of theophylline. The presented setup is a material and cost-saving approach for studying the influence of different process parameters on dehydration behavior during pharmaceutical processing.

Desiccation↗

PubMed2003

Physical stability of a microcrystalline beta-sitosterol suspension in oil.

Sterols have been shown to reduce plasma cholesterol by blocking the absorption of cholesterol from the gut. The physical properties of crystalline plant sterols limit their use in foods. A coarse-grained structure can be avoided by recrystallisation, a method that affords a reduction in the particle size. A previous work described how to produce a microcrystalline beta-sitosterol suspension. The present study deals with the stability of that suspension. Recrystallisation was carried out by two different methods; one based on rapid the other based on slow cooling, whereby six different compositions were made containing 5-30% of beta-sitosterol and secondly either 5 or 20% water was added. The particle size and habit were evaluated during a 16 weeks storage period (+4 or -19 degrees C) by way of optical microscopy. The crystal structure and degree of crystallinity was analysed by X-ray diffraction. Suspensions can, in most cases, be stored for 16 weeks without any changes to the size and habit. The only evidence of crystal growth came from a suspension with a low sterol concentration at a temperature of +4 degrees C. This is due to the dissolution-diffusion process which is affected by temperature and viscosity. Suspensions containing higher amounts of sterol remained stable, if stored at +4 or -19 degrees C, for 16 weeks. The suspensions included both hemihydrous and monohydrous beta-sitosterol crystals. Suspensions containing less sterol showed greater amounts of monohydrated crystals. This illustrates more water penetration into the crystals. A higher sterol concentration led to a larger number of smaller crystals creating reflections similar to hemihydrated crystals.

Cholesterol↗

PubMed2003

A novel technique for imaging film coating defects in the film-core interface and surface of coated tablets.

Confocal laser scanning microscopy (CLSM) was introduced and examined as a novel technique for imaging film-core interface and surface defects of film-coated tablets. Tablets of acetylsalicylic acid, microcrystalline cellulose (MCC) and lactose monohydrate were film-coated with aqueous hydroxypropyl methylcellulose using an instrumented side-vented pan coater. The film coatings were applied using 100- and 500-kPa spraying air pressures. The CLSM images of the coating surface were compared with surface roughness measurements using a laser profilometer and an optical roughness analyzer. The spraying air pressure affected the film-core interface and the occurrence of coating defects. With the lower spraying pressure the aqueous coating solution penetrated into the tablet core, the core components migrated to the coating layer, and the film coating surface was clearly rougher compared to the higher spraying pressure. Storage at 25 degrees C/60% RH or 40 degrees C/75% RH for 3 months expanded the MCC-containing tablet core impaired the film structure and increased the film roughness. Based on the present results, CLSM is an effective tool for imaging film-core interface and surface defects of film-coated tablets. The CLSM images are supported by the results obtained with the other surface roughness measuring techniques.

Microscopy, Confocal↗

PubMed2003

A novel amylose corn-starch dispersion as an aqueous film coating for tablets.

A novel aqueous coating dispersion of amylose-rich corn starch (Hylon VII) was evaluated in an aqueous film-coating process of tablets using an instrumented laboratory-scale pan-coating apparatus. The influence of two independent process variables, the coating temperature and the atomizing air pressure, on the properties of the coated tablets were investigated. The preuse stability of aqueous coating dispersion (i.e., amylose corn-starch precipitate) was studied using a powder X-ray diffraction (XRD) technique. The crystallinity of amylose starch in the coating dispersion was found to increase slightly during 9 months of storage (in a refrigerator 6 +/- 2 degrees C). The film coatings of an aqueous amylose-rich starch dispersion were successfully applied onto tablets without any significant drawbacks, such as nozzle blockage or related problems. It was found that the temperature in the coating pan had a significant influence on the film surface roughness, mechanical strength, and drug release in vitro. When the lowest coating temperature (30 degrees C) was used, rougher film coatings were obtained due to overwetting. At higher temperatures (up to 50-60 degrees C), lower surface roughness and higher mechanical strength values for the coated tablets were obtained. With the present amylose starch dispersion, the atomizing air pressure had a minor influence on the quality of the coating. Under appropriate coating conditions, a smooth tablet film coating was produced with this new, natural, and inexpensive amylose starch dispersion.

Amylose↗

PubMed2003

Influence of the aqueous film coating process on the properties and stability of tablets containing a moisture-labile drug.

The effects of an aqueous film coating process on the morphology and storage stability of hydroxypropyl methylcellulose-coated tablets containing a moisture-labile model drug (acetylsalicylic acid, ASA) were evaluated using an instrumented side-vented tablet pan coater. Coating parameters studied were inlet air absolute humidity 5 g/m3 and 12 g/m3, spraying air pressure 100 kPa and 500 kPa, pan air temperature 35 degrees C and 55 degrees C, and coating solution flow rate 2.2 g/min and 7.8 g/min. The surface roughness of the coatings was measured with a laser profilometer and the chemical hydrolysis of the model drug ASA with an UV-spectrophotometer. The film-coated tablets were stored at 25 degrees C/60% RH and 40 degrees C/75% RH for three months. The high absolute humidity of the inlet air increased the residual water content and surface roughness of the coated tablets. Using a lower coating solution flow rate, higher spraying air pressure and pan temperature the coatings were smooth and homogeneous. In both ambient and accelerated storage conditions, the roughness of the coatings and the hydrolysis of ASA increased, but this was independent of the film coating process. Uniform and smooth hydroxypropyl methylcellulose coatings can be achieved by improved control of process parameters related to the application of the coating solution and water evaporation of the tablet surface.

Air Movements↗

PubMed2003

Influence of solvents on the variety of crystalline forms of erythromycin.

The influence of the organic solvents widely used in the pharmaceutical industry (acetone, methylethylketone, ethanol, and isopropanol) both in the presence and in the absence of water on the crystallization behavior of erythromycin (Em), a clinically relevant antibiotic of the macrolide group, was investigated. It was observed that despite a high preference for water as a guest molecule, Em rather easily forms solvates with the organic solvents studied. Consequently, 4 distinct solvates of Em have been isolated by recrystallization: acetonate, methylethylketonate, ethanolate, and isopropanolate. It was established that in a pure organic solvent, or 1:9 or 1:1 water-organic solvent mixtures, the corresponding solvate is always crystallized. However, the recrystallization of erythromycin from 2:1 water-organic solvent (excluding methylethylketone) mixture results in the formation of a crystal hydrate form. X-ray powder diffraction revealed the isostructurality of the solvates with acetone and methylethylketone. Thermogravimetric analysis showed that the loss of volatiles by all of the solvated crystals is nonstoichiometric. The desolvation behavior of the solvates with the organic solvents studied by means of variable-temperature x-ray powder diffraction indicates that in contrast to erythromycin dihydrate, they belong to a different class of solvates--those that produce an amorphous material upon desolvation.

Anti-Bacterial Agents↗

PubMed2003

Optimizing the crystal size and habit of beta-sitosterol in suspension.

The aim of this work was to survey how processing parameters affect the crystal growth of beta-sitosterol in suspension. The process variables studied were the cooling temperature, stirring time and stirring rate during recrystallization. In addition, we investigated the effect a commonly used surfactant, polysorbate 80, has on crystal size distribution and the polymorphic form. This study describes the optimization of the crystallization process, with the object of preparing crystals as small as possible. Particle size distribution and habit were analyzed using optical microscopy, and the crystal structure was analyzed using X-ray diffractometry. The cooling temperature had a remarkable influence on the crystal size. Crystals with a median crystal length of approximately 23 microm were achieved with a low cooling temperature (<10 degrees C); however, a fairly large number of crystals over 50 microm appeared. Higher cooling temperatures (>30 degrees C) caused notable crystal growth both in length and width. Rapid (250 rpm), continuous stirring until the suspensions had cooled to room temperature created small, less than 50 micro m long (median <20 microm), needle-shaped crystals. The addition of surfactant slightly reduced the size of the initially large crystals. Both hemihydrate and monohydrate crystal forms occurred throughout, regardless of the processing parameters. By using an optimized process, it was possible to obtain a microcrystalline suspension, with a smooth texture.

Chemistry, Pharmaceutical↗

PubMed2003

Effects of microcrystalline plant sterol suspension and a powdered plant sterol supplement on hypercholesterolemia in genetically obese Zucker rats.

Because dietary fat appears to be an effective vehicle for dispensing plant sterols into the diet, a special plant-sterol-containing ingredient has recently been developed. This ingredient is a plant sterol suspension in oil in which the sterols are in microcrystalline form. The objective of the present study was to analyse the cholesterol-lowering effects and safety of two different plant sterol preparations, an orally administered microcrystalline plant sterol suspension (MPS) in rapeseed oil and a powdered plant sterol supplement, in obese Zucker rats. Dietary plant sterol supplements (0.5%, w/w) were given concurrently with a high cholesterol diet (HCD, 1% cholesterol and 18% fat, w/w). No significant changes in serum triglyceride, blood glucose, serum glutamate oxaloacetic transaminase and glutamic pyruvic transaminase values or body and liver weights were observed. The powdered plant sterol supplement lowered the serum cholesterol by 25% (P < 0.05) and the MPS diet by 35% (P < 0.001) compared with HCD by the end of the 12-week experiment. Interestingly, the plant sterol supplements also produced a marked reduction in serum ubiquinone levels, suggesting a possible effect on isoprene synthesis. Unlike the powdered plant sterol, both MPS and plain rapeseed oil decreased the serum baseline diene conjugation values, suggesting that they protect against oxidative stress-induced lipid peroxidation in rats. This lipid peroxidation diminishing effect is probably due to some antioxidative components in rapeseed oil. These findings indicate that an unesterified plant sterol, such as the microcrystalline suspension in oil, effectively prevents cholesterol absorption in obese Zucker rats.

Administration, Oral↗