Biomedical subjects

Peter Kleinebudde

Publications and source records attributed to Peter Kleinebudde.

At least 19 recordsLinked to original sources

PubMed2006

Influence of scale-up on the abrasion of tablets in a pan coater.

The purpose of this study was to examine the influence of batch size during scale-up on the abrasion and edge splitting of flat faced lactose tablets. The weight loss of white tracer tablets in a batch of blue coated tablets was investigated in a laboratory scale pan coater and a pilot scale pan coater as a function of different pan speeds and mixing times. It was observed that increasing batch size resulted in a decreased weight loss due to less edge damaging. The higher number of tablet impacts at the pan wall in the laboratory scale compared to the pilot scale might be the reason for this phenomenon. The common assertion that an increase in batch size in scale-up leads to a higher abrasion or tablet damaging was not supported in the current study.

Chemistry, Pharmaceutical↗

PubMed2006

Mathematical modeling of an aqueous film coating process in a Bohle Lab-Coater, part 1: development of the model.

The purpose of this study was to develop a model to predict (1) air and product temperatures, (2) product moisture, and (3) air humidity during an aqueous coating process using a Bohle Lab-Coater. Because of the geometrical properties and the airflow, the drum of the Bohle Lab-Coater can in principle be divided into 2 zones of equal size-the drying and the spraying zones. For each zone, 4 balance equations could be set up describing the change of the air humidity, the product moisture, the enthalpy of the air, and the enthalpy of the product in each zone. For this purpose, knowledge regarding heat and mass transfer and also the motion of the tablets in drums was used. Based on the considerations of the heat and mass transfer, a set of first-order coupled ordinary differential equations (ODEs) was developed. This set of ODEs can be solved numerically. In this part, the development of the model is described in detail, whereas the application of the model can be found in part 2.

Chemistry, Pharmaceutical↗

PubMed2006

Mathematical modeling of an aqueous film coating process in a Bohle Lab-Coater: part 2: application of the model.

For the prediction of the air and product temperatures, the product moisture, and the air humidity during a coating process in a Bohle Lab-Coater, a model was developed. The purpose of this work was to determine the limit moisture, the critical moisture, and the constant for the exchange rate between both zones and to use these values for other sets of experiments to test the model. The adaptation of the 3 parameters (limit moisture, critical moisture, and exchange rate constant) was done by calculation of the product temperature in both zones for several sets of parameters in order to minimize the sum of square deviation between the calculated and the measured product temperatures. This set of parameters was used to test the validity of the model. By applying the model, the product temperature could be predicted based on the product, process, and equipment-related parameters. Hence, the model can be used to theoretically investigate the influence of different process parameters. The mean difference between the predicted and measured product temperatures in the steady state is approximately 2 up to 3 K using the determined parameter set for the limit moisture, the critical moisture, and the exchange rate constant. The model is useful for the prediction of the air and product temperatures, the product moisture, and air humidity during a coating process in the Bohle Lab-Coater using round, biconvex tablets.

Chemistry, Pharmaceutical↗

PubMed2006

Comparison study of laboratory and production spray guns in film coating: effect of pattern air and nozzle diameter.

An optimal atomization air/pattern air ratio is necessary for a good coating process. The influences of variations in pattern air and nozzle diameter on the spray characteristics, such as droplet size, droplet velocity, and spray density, are investigated by using laboratory and production Schlick spray guns, both equipped with a new antibearding cap (ABC). An increase in the pattern air results in a wider spray accompanied with a decrease in droplet size in the spray center for both spray guns. Furthermore, an increase in the pattern air leads to a reduction in spray density in the spray center and, simultaneously, to an increase in spray density at the spray rim. A variation in nozzle diameter does not influence the spray characteristics for both spray guns.

Chemistry, Pharmaceutical↗

PubMed2005

Use of kappa-carrageenan as alternative pelletisation aid to microcrystalline cellulose in extrusion/spheronisation. I. Influence of type and fraction of filler.

Microcrystalline cellulose (MCC) is commonly used as an excipient in extrusion/spheronisation process. However, MCC has several disadvantages as lack of disintegration and drug adsorption. Therefore, kappa-carrageenan was investigated to substitute MCC in pelletising processes. Formulations with 20% of pelletisation aid (kappa-carrageenan or MCC) and acetaminophen as a model drug have been produced. Different fillers (lactose, mannitol, maize starch and dicalciumphosphate dihydrate) at fractions of 0, 20, 40 and 80% were evaluated and the properties of the resulted pellets were determined (e.g. yield, aspect ratio, mean Feret diameter, 10% interval fraction, tensile strength and release profile). kappa-Carrageenan has proven to be a suitable substitute as pellets with sufficient quality were produced. The pellet batches of different formulations were characterised by high yield, spherical pellet shape and narrow pellet size distribution. The distinguished behaviour between kappa-carrageenan and MCC pellets was the lower tensile strength and the faster release of kappa-carrageenan pellets. For the various types and fractions of fillers only minor effects to the pelletisation process and pellet properties were noticed. From the practical view these effects are neglectable indicating a robust formulation and process.

Acetaminophen↗

PubMed2005

Use of kappa-carrageenan as alternative pelletisation aid to microcrystalline cellulose in extrusion/spheronisation. II. Influence of drug and filler type.

The extrusion/spheronisation process is an established technique to produce pellets for pharmaceutical applications. Microcrystalline cellulose (MCC) is being usually used as a pelletisation excipient in the extrusion process. However, MCC has some disadvantages, e.g. lack of disintegration and prolonged drug dissolution. Therefore, kappa-carrageenan was investigated as a substitute for MCC to overcome such disadvantages. A fixed ratio of kappa-carrageenan (20%) was combined with different fillers (lactose, mannitol, maize starch and dicalciumphosphate dihydrate) and different drugs (acetaminophen, theophylline, mesalamine and hydrochlorothiazide) in several formulations. Some pellet properties (yield, aspect ratio, mean Feret diameter, 10% interval fraction, tensile strength and dissolution profile) were determined. Most formulations resulted in pellets of a sufficient quality with respect to size, size distribution and shape independent of the incorporated fillers and drugs. In contrast to MCC pellets, the release profile of kappa-carrageenan pellets was much less affected by the solubility of the drug. Generally, kappa-carrageenan pellets owned fast disintegration and fast drug release in contrast to MCC pellets.

Acetaminophen↗

PubMed2005

Studies of the retrogradation process for various starch gels using Raman spectroscopy.

The retrogradation of untreated wild-type starches (potato, maize, and wheat), waxy maize starches, and one pregelatinized, modified amylose-rich starch was investigated continuously using Raman spectroscopy. The method detects conformational changes due to the multi-stage retrogradation, the rate of which differs between the starches. The pregelatinized, modified amylose-rich starch shows all stages of retrogradation in the course of its Raman spectra. In comparison to amylose, the retrogradation of amylopectin is faster at the beginning of the measurements and slower in the later stages. The untreated starches can be ranked in the order of their rate of retrogradation as follows: potato>maize>wheat.

Amylopectin↗

PubMed2005

Preliminary assessment of carrageenan as excipient for extrusion/spheronisation.

The current study pursues the suitability of different types of carrageenan as a novel extrusion aid. The aim was to find out a suitable substitution to the commonly used microcrystalline cellulose (MCC). The types of kappa-carrageenan were found to be the most appropriate material and the required fraction to produce acceptable pellets in the formulation was determined. The investigation showed that 5% of kappa-carageenan was necessary to produce pellets without MCC. Similar formulations produced with MCC or kappa-carrageenan were compared with respect to size and shape of the pellets. kappa-Carrageenan required higher water content for the formation of pellets, but the formulation was more robust as the optimal range of water content was much broader. Hence, kappa-Carrageenan seems to be a suitable and promising extrusion aid. The study showed that the substitution of MCC by kappa-carrageenan in formulations is possible and the produced pellets were of high quality.

Carrageenan↗

PubMed2005

Coprocessing of powdered cellulose and magnesium carbonate: direct tableting versus tableting after roll compaction/dry granulation.

Mixtures of magnesium carbonate (MC) with three types of powdered cellulose (M80, P290, A300) were tableted directly or after roll compaction/dry granulation. The fraction of powdered cellulose in the mixture was varied from 0% to 25% (w/w). The properties of the granules, blends, and their corresponding tablets were analyzed. Granules with a low amount of A300 showed the best flow properties, whereas the fibrous shape of the binding agents M80 and P290 impaired the free flow. Heckel plots showed clearly the different behavior of powdered cellulose in blends and granules during the tableting process. The Heckel-Plots for pure MC powder and granulated MC (MCgr) were similar. Increasing the fraction of powdered cellulose resulted in a fan-shaped set of curves, which is a reflection of an increased densification. Physical mixtures of all three powdered celluloses and granulated mixtures of M80 resulted in a higher densification compared with pure MC. In contrast, the granulated mixtures of P290 and A300 resulted in a diminished densification during tableting, which means that the coprocessed mixtures behaved differently during tableting compared with the physical mixtures. The curves were lower than those of pure MC and MCgr most pronounced at a fraction of 5% powdered cellulose. The tablet pore structure was evaluated by mercury porosimetry. The addition of P290 and A300 to the dry granules resulted in tablets with a higher fraction of smaller pores. Comparably high values for tablet tensile strength and low friability resulted from this special tablet structure. Roll compacted/dry granulated MC, coprocessed with 5% of P290 or A300, seems to be a promising excipient for direct compression. This coprocessed product combines good flow and tablet properties, and is superior to pure MC or a physical mixture of MC and PC.

Cellulose↗

PubMed2004

Roll compaction/dry granulation: pharmaceutical applications.

Roll compaction/dry granulation (RCDG) is an agglomeration process of growing importance. New machine generations and improvements in instrumentation and process control have resulted in an increasing number of pharmaceutical applications of RCDG. This literature review illustrates the progress and the use of RCDG in the production of directly compressible excipients, the compaction of drugs and drug formulations, the granulation of inorganic materials, the granulation of dry herbal material and the production of immediate/sustained release formulations.

Chemistry, Pharmaceutical↗

PubMed2004

How do roll compaction/dry granulation affect the tableting behaviour of inorganic materials? Microhardness of ribbons and mercury porosimetry measurements of tablets.

The effect of roll compaction/dry granulation on the ribbon and tablet properties produced using different magnesium carbonates was evaluated. The ribbon microhardness and the pore size distribution of tablets were used as evaluation factors. Increasing the specific compaction force resulted in higher microhardness for ribbons prepared with all four magnesium carbonates accompanied with decreased part of fine. Consequently, the corresponding produced tablets displayed a lower tensile strength. A possible correlation between the particle shape, surface area and the resulting pore structure of tablets produced with the four different types of magnesium carbonate was observed. The tensile strength of tablets prepared using granules was lower than tensile strength of tablets produced using starting materials. The partial loss of compactibility resulted in a demand of low loads during roll compaction. However, the impact of changes in the material properties during the roll compaction depended greatly on the type of magnesium carbonate, the specific compaction force and the tableting pressure applied.

Chemistry, Pharmaceutical↗

PubMed2003

Properties of microcrystalline cellulose and powder cellulose after extrusion/spheronization as studied by fourier transform Raman spectroscopy and environmental scanning electron microscopy.

In this study, the effect of powder cellulose (PC) and 2 types of microcrystalline cellulose (MCC 101 and MCC 301) on pellet properties produced by an extrusion/spheronization process was investigated. The different investigated types of cellulose displayed different behavior during the extrusion/spheronization process. Pure PC was unsuitable for extrusion, because too much water was required and the added water was partly squeezed during the extrusion process. In contrast, MCC 101 and MCC 301 were extrudable at a wide range of water content, but the quality of the resulting products varied. In the extrusion/spheronization process, MCC 101 was the best substance, with easy handling and acceptable product properties. The properties of the extrudates and pellets were determined by Fourier transform (FT) Raman spectroscopy and environmental scanning electron microscopy (ESEM). FT-Raman spectroscopy was able to distinguish between the original substances and also between the wet and dried extrudates. The particle sizes of the raw material and of the extrudates were determined by ESEM without additional preparation. For MCC, the size of the resulting particles within the extrudate or pellet was smaller. However, in the extrudates of PC, changes in particle size could not be observed.

Cellulose↗

PubMed2003

How do roll compaction/dry granulation affect the tableting behaviour of inorganic materials? Comparison of four magnesium carbonates.

The effect of roll compaction/dry granulation on the particle and bulk material characteristics of different magnesium carbonates was evaluated. The flowability of all materials could be improved, even by the application of low specific compaction forces. The tablet properties made of powder and dry granulated magnesium carbonate were compared. Roll compaction/dry granulation resulted in a modified compactibility of the material and, consequently, tablets with reduced tensile strength. The higher relative tap density of the compacted material does not allow a densification to the same extent as the uncompacted powder. The degree of densification during tableting can be expressed as the ratio of the relative tablet density to the relative tap density of the feed material. Increasing the specific compaction forces resulted in higher apparent mean yield pressure, gained from Heckel plots, of all materials analysed. The partial loss of compactibility leads to the demand of low loads during roll compaction. Comparing the tablet properties of different magnesium carbonates reveals an obvious capping disposition. However, it depends on the type of magnesium carbonate, the specific compaction force and also on the tableting force applied.

Chemistry, Pharmaceutical↗

PubMed2003

Coating uniformity and coating efficiency in a Bohle Lab-Coater using oval tablets.

The aim of this study was the examination of the influence of tablet size (two different sized oval tablets), batch size, pan speed and inclination of the rotation axis on the coating uniformity and efficiency in a Bohle Lab-Coater BLC 5. The coating uniformity was appraised using the mass variance, the dissolved amount of acetaminophen after 2 h in hydrochloric acid pH 1.0 at a polymer loading of 3 mg/cm(2) and the minimum amount of polymer for an enteric coating. The mass variance of the final tablets decreased with increasing pan speed. There was a linear and quadratic effect in the case of small oval tablets and a linear effect for the large tablets. The minimum amount of polymer required for gastric resistance depends on the pan speed for both tablet sizes. The dissolved amount of acetaminophen after 2 h in simulated gastric fluid was influenced linearly by the batch size for both kind of tablets. In the case of the large oval tablets it was also influenced by the pan speed, the batch size and the inclination of the rotation axis. The dissolved amount of acetaminophen increased with increasing pan speed and batch size. A relation between the coating process efficiency and the investigated influence variables could not be established.

Acetaminophen↗

PubMed2003

Disintegrating pellets from a water-insoluble pectin derivative produced by extrusion/spheronisation.

Pectinic acid (PA) and microcrystalline cellulose (MCC) as extrusion aiding excipients have been compared. Three different drugs were selected as models: Riboflavin with a very low water solubility, paracetamol and theophylline as drugs with high water-solubility. The drug load was varied from 1 to 80% wt. The low-soluble pectin derivative, PA (degree of methoxylation <10%) was found to be well suited as an extrusion aiding excipient in pellet preparation by extrusion/spheronisation. The substance has a high drug loading capacity and produces disintegrating pellets that are well suited for fast delivery of drugs with a low water-solubility. The pellets are also mechanically stable. Compared to MCC, PA was found to require less water for pellet formation and was more sensitive against changes in the water content. In order to achieve optimal shape of the pellets, spheronisation was carried out at 45 degrees C. PA is more sensitive to type and amount of drug and is, consequently, not as universally applicable as the conventionally used microcrystalline cellulose. The great advantage of pectinic acid is, however, the disintegrating properties of the pellets after only a short time of exposure to liquid.

Drug Implants↗

PubMed2003

Pediatric drug formulations of sodium benzoate: II. Coated granules with a lipophilic binder.

Sodium benzoate is used as a therapeutic agent in the treatment of some rare disorders that predominantly affect children. In preliminary investigations, liquid and semi-solid formulations of sodium benzoate failed because children refuse the oral uptake due to the bad taste of the drug. Recently developed microcapsules with macrogol as a hydrophilic binder raise concern in high-dose treatment regimens because acceptable daily intake limits are exceeded. A novel microcapsule formulation was developed consisting of a lipophilic core with high sodium benzoate load and a saliva-resistant coating. A new powder quality of saturated triglycerides from plant origin was introduced which complies with the Ph. Eur. monograph 'Hard fat'. Sodium benzoate and the triglyceride were mixed and directly extruded at room temperature. The extrudates were spheronized and coated in a fluidized-bed process. The resulting coated granules are small-sized microcapsules and taste neutrally. They can be mixed with food before administration. As the amount of released sodium benzoate is negligible within the first minutes, children do not recognize the bad taste and accept the medication. Recently, sodium benzoate in this novel formulation has been designated by the European Community as an orphan drug in the treatment of non-ketotic hyperglycinemia.

Capsules↗

PubMed2003

Pediatric drug formulations of sodium benzoate: I. Coated granules with a hydrophilic binder.

High doses of sodium benzoate are applied in the treatment of some rare metabolic disorders. In most cases children are affected who often refuse the oral uptake of sodium benzoate as a powder or in solution due to its bad taste. Therefore, small-sized, saliva-resistant microcapsules have been developed containing high doses of the drug substance. Granules were produced by roller compacting of sodium benzoate powder without any additives, by solvent-free cold extrusion and hot-melt extrusion adding poly(ethylene glycol)s of different grades. The granules with a diameter of less than 1 mm were film-coated by an ethanolic solution of Eudragit E 100. The microcapsules from hot-melt extrusion containing 25% Macrogol 4000 were most stable during the coating process and showed the highest yields. Sodium benzoate is completely released from the microcapsules within 9 min into 0.1 N HCl and 0.01 N HCl whereas dissolution into buffer pH 6.8 is different in the initial phase and completed after 14 min. The bad taste of sodium benzoate is not recognized in the buccal space for at least 5 min. The microcapsules are stable during storage for at least 6 months.

Capsules↗

PubMed2003

Coating uniformity: influence of atomizing air pressure.

The objective of this study was to investigate the influence of atomizing air pressure on the coating uniformity and the quality of the film coat. As parameters describing the coating uniformity, the mass variance of the film coated tablets and the variance of the film thickness within a tablet were used. For the examination of the properties of the film coat, the cumulative frequency of the tablet mass, the spray loss, the relative frequency of the film thickness, the minimum amount of polymer required for an enteric coating, and the swelling number were taken into consideration. For this study a Walther Pilot spray gun WA 50 with a liquid orifice diameter of 0.5 mm and a flat jet air cap was used. The experiments were carried out in a Bohle BLC 5 drum coater using four different atomizing air pressures between 0.5 and 2.0 bar. All other parameters were kept constant during the coating process. It could be shown that atomizing air pressure is an important factor influencing the quality and uniformity of a film coat. An increase in the atomizing air pressure will produce smooth tablets with a small mass variance. Due to a greater spray loss, the required minimum amount of polymer for an enteric coating is higher at an atomizing air pressure of 2.0 bar.

Air Pressure↗