Moisture-Activated dry Granulation in a high Shear Mixer

The applicability of a 25 litre high shear mixer for moisture-activated dry granulation was examined. Microcrystalline cellulose, potato starch or a mixture of 50% m/m of each was used as moisture absorbing material. The effects of water content, wet massing time, moisture absorbing material and dry mixing time on the size distribution, and the compressibility of the granulations were investigated. Tablets were compressed on a single punch press from all the granulations and on a rotary press from a few of the granulations.

It was shown that the physical properties of the tablets were primarily affected by the water content, the moisture absorbing material, and the compression force. Tablets with low mass variation, high crushing strength, low friability, and short disintegration time were achieved with both tablet presses by using a mixture of microcrystalline cellulose and potato starch as moisture absorbing material.     

Wet Granulation in a Small Scale High Shear Mixer

Abstract

Wet granulation of lactose and corn starch in a 10 litre high shear mixer was examined. The effect of the amount of water added, granulation time and impeller speed on five properties of the granules was investigated by a response surface design.

It was shown that moisture level as a major effect on geometric mean diameter and flow rate of the granules. The impeller speed markedly influences the geometric mean diameter, geometric standard deviation, compactability index and percentage of granules smaller than 1250 μm. Finally the granulation time has an evident influence on compactability index.

Theoretical optimum conditions were obtained for the five response variables and are comparable with the experimental results.     

Wet Granulation in a Small Scale High Shear Mixer

Wet granulation of lactose and corn starch in a 10 litre high shear mixer was examined. The effect of the amount of water added, granulation time and impeller speed on five properties of the granules was investigated by a response surface design.

It was shown that moisture level as a major effect on geometric mean diameter and flow rate of the granules. The impeller speed markedly influences the geometric mean diameter, geometric standard deviation, compactability index and percentage of granules smaller than 1250 μm. Finally the granulation time has an evident influence on compactability index.

Theoretical optimum conditions were obtained for the five response variables and are comparable with the experimental results.     

Melt Granulation in A Laboratory Scale High Shear Mixer

The applicability of a 10 litre high shear mixer for melt granulation of dicalcium phosphate and lactose is examined. Polyethylene glycol (PEG) 3000 and 6000 were used as melting binders in concentrations of 15-20% w/w. The effects of binder concentration, massing time, impeller speed, and particle size of the PEG 6000 on granule size, granule size distribution and intragranular porosity are investigated.

It is shown that pellets of a narrow size distribution can be produced by the use of a high impeller speed. Granule size and size distribution are markedly influenced by binder concentration and massing time. The particle size of the PEG has only a minor effect on the granule growth. Granule growth mechanisms by melt granulation are discussed on the basis of the liquid saturations and the amounts of binder liquid and are compared with previous results on wet granulation.     

Melt Granulation in A Laboratory Scale High Shear Mixer

Abstract

The applicability of a 10 litre high shear mixer for melt granulation of dicalcium phosphate and lactose is examined. Polyethylene glycol (PEG) 3000 and 6000 were used as melting binders in concentrations of 15-20% w/w. The effects of binder concentration, massing time, impeller speed, and particle size of the PEG 6000 on granule size, granule size distribution and intragranular porosity are investigated.

It is shown that pellets of a narrow size distribution can be produced by the use of a high impeller speed. Granule size and size distribution are markedly influenced by binder concentration and massing time. The particle size of the PEG has only a minor effect on the granule growth. Granule growth mechanisms by melt granulation are discussed on the basis of the liquid saturations and the amounts of binder liquid and are compared with previous results on wet granulation.     

A Comparison Between Binders in the Wet Phase of Granulation in a High Shear Mixer

The effects of binder solutions on granule size, intragranular porosity and liquid saturation in a high shear mixer are examined during the liquid addition phase of the granulation process. The power consumption profiles of impeller motor are recorded. Five different binders (PVP, PVP-PVA-copolymer, hydrolysed gelatine and two HPMC'S) are investigated.

The PVP and hydrolysed gelatine produce granules with a higher mean granule size. This is shown to be due to the higher densification caused by these binders.

The power consumption profiles for PVP are significantly higher than for the other binder solutions. It is suggested that the high power consumption profiles are a result of the strength of mobile liquid bondings caused by the high surface tension of PVP solutions.     

A Comparison Between Binders in the Wet Phase of Granulation in a High Shear Mixer

The effects of binder solutions on granule size, intragranular porosity and liquid saturation in a high shear mixer are examined during the liquid addition phase of the granulation process. The power consumption profiles of impeller motor are recorded. Five different binders (PVP, PVP-PVA-copolymer, hydrolysed gelatine and two HPMC'S) are investigated.

The PVP and hydrolysed gelatine produce granules with a higher mean granule size. This is shown to be due to the higher densification caused by these binders.

The power consumption profiles for PVP are significantly higher than for the other binder solutions. It is suggested that the high power consumption profiles are a result of the strength of mobile liquid bondings caused by the high surface tension of PVP solutions.     

Influence of Liquid Bonding Strength on Power Consumption During Granulation in a High Shear Mixer

Abstract

A comparison between the effects of different binders on power consumption and -granule growth by granulation in a Fielder PMAT 25 high shear mixer demonstrates that the power consumption is influenced by the intra-granular porosity and the surface tension of the binder solution. It is suggested that the effects are due to a correlation between the power consumption and the strength of mobile liquid bondings in the moist agglomerates. It is shown that the power consumption reflects the change of the intragranular porosity for a particular granulation process with dicalcium phosphate.     

Granulation of Lactose in a Domestic-Type Mixer

When process variables controlling the droplet size and the distribution of the granulating liquid in the powder, i.e. the liquid flow rate, the way of adding the liquid and the wet massing time, are controlled during the granulation of lactose 350 mesh with water in a recording laboratory mixer, the amount of water added determines the torque of the mixing bowl. The torque value can be used as an indication of the granule size.     

Comparison of Moisture-Activated Dry Granulation Profess with Conventional Granulation Methods for Sematilide Hydrochloride Tablets

During the development of a tablet formulation of a cohesive, fluffy investigational drug, a novel moisture-activated dry granulation (MADG) process was studied in comparison with two conventional granulation methods, i.e., wet granulation and dry granulation with a roller compactor, as well as with a direct compression formulation method. The MADG method produced granules with excellent flowability which were equivalent in a number of ways to those produced by either conventional wet granulation or dry granulation methods and which were much better than the powder blend from the direct compression formulation. The tablets prepared using the MADG method had better content uniformity than those made using material from wet and dry granulation processes. Other tablet properties, such as weight variation, friability and dissolution, were similar among the tablets produced by the four processes     

Granulation of Lactose in a Recording High-Speed Mixer, Diosna P25

When the conditions involved in the granulation process — inter alia liquid flow rate, atomization conditions, impeller and chopper speed, and amount of powder — were fixed, it was possible to determine the end-point of the graulation of lactose with a gelatin solution on the basis of rotation-rate changes affecting the main impeller shaft.     

Granulation of Lactose in a Recording High-Speed Mixer,Diosna P25

Abstract

When the conditions involved in the granulation process — inter alia liquid flow rate, atomization conditions, impeller and chopper speed, and amount of powder — were fixed, it was possible to determine the end-point of the graulation of lactose with a gelatin solution on the basis of rotation-rate changes affecting the main impeller shaft.     

Instrumentation of a Kenwood Major Domestic-Type Mixer for Studies of Granulation

The mixer was reconstructed and equipped with a torque transducer consisting of a steel beam, with strain gauges in a full bridge circuit, which prevented the rotation of the bowl.

Repeated loadings of the separate steel beam with weights resulted in a relative standard deviation of less than 0.2%. However, tangential loading of the equipment with a dynamometer resulted in a relative standard deviation of 1.2% because of the inaccuracy of the dynamometer load. The smallest detectable load was about 98· 10^-3 N, corresponding to 1-2% sensitivity within the interesting part of the granulation curve.

The average torque was calculated.

The recording mixer was simple to handle and proved a suitable tool for granulation studies.     

Instrumentation of a Kenwood Major Domestic-Type Mixer for Studies of Granulation

The mixer was reconstructed and equipped with a torque transducer consisting of a steel beam, with strain gauges in a full bridge circuit, which prevented the rotation of the bowl.

Repeated loadings of the separate steel beam with weights resulted in a relative standard deviation of less than 0.2%. However, tangential loading of the equipment with a dynamometer resulted in a relative standard deviation of 1.2% because of the inaccuracy of the dynamometer load. The smallest detectable load was about 98· 10^-3 N, corresponding to 1–2% sensitivity within the interesting part of the granulation curve.

The average torque was calculated.

The recording mixer was simple to handle and proved a suitable tool for granulation studies.     

The Granulation of a Tablet Formulation in a High-Speed Mixer,Diosna P 25

Abstract

The impeller speed, the loss-on-drying of starch, and the added amount of water significantly influenced these response variables: granule fractions of less than 0.150 mm and more than 2.00 mm; and granule median diameter. The influence of the drug concentration on the response variables was less important. All the response variables showed significant interactions.

At a fixed impeller speed, the fine fraction was reduced when the loss-on-drying of starch increased, and when water was added in increasing amounts. The coarse fraction and granule median diameter increased along with an increasing moisture content in the starch. Increasing amounts of added water had the same effect.

The response surface contours of a fraction less than 0.150 mm, and a fraction exceeding 2.00 mm, were plotted. So was the granule median diameter. Suitable levels for the processing variables involved in obtaining a granulation of the desired proportions - fine or coarse fraction - can be read from the contour plots.

Heat was generated in the mixer during kneading, which caused some evaporation of water.

The change in the rotation rate of the impeller during the addition of the granulating liquid can be used as an indication of the fraction percentages below 0.150 mm and above 2.00 mm, but not of the median diameter     

The Granulation of a Tablet Formulation in a High-Speed Mixer, Diosna P 25

The impeller speed, the loss-on-drying of starch, and the added amount of water significantly influenced these response variables: granule fractions of less than 0.150 mm and more than 2.00 mm; and granule median diameter. The influence of the drug concentration on the response variables was less important. All the response variables showed significant interactions.

At a fixed impeller speed, the fine fraction was reduced when the loss-on-drying of starch increased, and when water was added in increasing amounts. The coarse fraction and granule median diameter increased along with an increasing moisture content in the starch. Increasing amounts of added water had the same effect.

The response surface contours of a fraction less than 0.150 mm, and a fraction exceeding 2.00 mm, were plotted. So was the granule median diameter. Suitable levels for the processing variables involved in obtaining a granulation of the desired proportions - fine or coarse fraction - can be read from the contour plots.

Heat was generated in the mixer during kneading, which caused some evaporation of water.

The change in the rotation rate of the impeller during the addition of the granulating liquid can be used as an indication of the fraction percentages below 0.150 mm and above 2.00 mm, but not of the median diameter     

Effect of Impeller and Chopper Design on Granulation in a High Speed Mixer

Abstract

Effects of impeller and chopper design upon granule growth are investigated by granulation of dicalcium phosphate in a Fielder PMAT 25 laboratory high speed mixer. It is shown that the effects of the impeller design with respect to the blade inclination and impeller rotation speed can be described in terms of the volume swept out by the impeller. A high swept volume causes high densification of the agglomerates and narrow granule size distributions. Chopper size and rotation speed have no effect upon the granule size distribution. It is suggested that the primary function of the chopper is to disturb the uniform flow pattern of the mass. Effects of deposition of moist mass on the wall of the bowl on granule growth are demonstrated, and suggestions for reducing the deposition are given.     

Effect of Impeller and Chopper Design on Granulation in a High Speed Mixer

Effects of impeller and chopper design upon granule growth are investigated by granulation of dicalcium phosphate in a Fielder PMAT 25 laboratory high speed mixer. It is shown that the effects of the impeller design with respect to the blade inclination and impeller rotation speed can be described in terms of the volume swept out by the impeller. A high swept volume causes high densification of the agglomerates and narrow granule size distributions. Chopper size and rotation speed have no effect upon the granule size distribution. It is suggested that the primary function of the chopper is to disturb the uniform flow pattern of the mass. Effects of deposition of moist mass on the wall of the bowl on granule growth are demonstrated, and suggestions for reducing the deposition are given.     

Optimization of Granulates in a High Shear Mixer by Mixture Design

Abstract

Optimization of wet granulation in a 10 litre high shear mixer was examined by mixture design. Lactose, corn starch and cellulose microcrystalline were used as eccipients of the granules. Mixing ratios of these eccipients were selected as formulation factors. In addition, the impeller speed and granulation time was employed as independent process variables. A two-phase experimental strategy was drawn up: one phase for the percentages of the three eccipients and the other phase for the determination of the influence of process variable on geometric mean diameter. The percentages were studied using a Scheffè simplex-centroid design, and the other phase was examined using a Doehlert experimental matrix.     

Use of a Motor Load Analyzer to Monitor the Granulation Process in a High Intensity Mixer

A motor load analyzer instrumented to a high intensity mixer was examined for its ability to monitor the granulation process with varying formulation and processing parameters. A lactose/microcrystalline cellulose blend with povidone as the binder was used as the test system.

The motor load analyzer was able to note chopper operation and liquid addition methods. However, it could not differentiate between povidone addition as an aqueous solution or as part of the lactose microcrystalline cellulose blend, followed by massing with water. The compression characteristics of the granulations depended upon chopper usage, and povidone and liquid amounts, and their methods of addition.