Adhesion of Tablets in a Rotary Tablet Press II. Effects of Blending Time,Running Time,and Lubricant Concentration

Abstract

Of the three essential functions of tablet lubricants, only the true lubricant and glidant properties have been studied in detail by objective means. Only recently has instrumentation which permits the objective measurement of the antiadhesion activity in a rotary tablet press been developed. Using a rotary press instrumented to measure the adhesion of tablets to the lower punch face, this study focuses on the adhesion of tablets in two direct compression systems. At any given compression force, adhesion of microcrystalline cellulose tablets lubricated with magnesium stearate appeared to decrease with increases in blending time or intensity of blending. Over a three-hour running time, adhesion force was found to increase to peak values and then to decline with both microcrystalline cellulose and hydrous lactose lubricated with magnesium stearate. However, ejection forces decreased gradually to apparently limiting values in each case. The adhesion of tablets to the lower punch face appeared to be affected partly by the condition of the tablet - die wall interface. Studies comparing lubricated and unlubricated microcrystalline cellulose suggest two opposing effects on tablet adhesion: (1) enhancing adhesion due to an increased reaction at the lower punch resulting from reduced die wall friction; and, (2) reducing the adhesion of tablets via the “antiadherent” effect. At the lubricant levels studied, stearic acid generally appeared to be less efficient than magnesium stearate in reducing both the adhesion and ejection forces in microcrystalline cellulose blends. However, with hydrous lactose blends, the true lubricant and antiadherent activities of stearic acid appeared to be greater than those of magnesium stearate at the 1.00% level of addition.     

Adhesion of Tablets in a Rotary Tablet Press I. Instrumentation and Preliminary Study of Variables Affecting Adhesion

This study describes instrumentation to Measure the adhesion of tablets to the lower punch face by means of a strain gaged cantilever beam affixed to the feed frame in front of the sweep-off blade. The tablet is detached from the lower punch by striking this blade. The adhesion force is the total force measured by the beam less that due to the momentum of the tablet. Tableting was performed on a Stokes RB-2 press previously instrumented to monitor compression and ejection forces. Generally, the higher the compression force, or the lower the magnesium stearate concentration, the higher the adhesion in three direct compression fillers (compressible sugar, microcrystalline cellulose, lactose). With microcrystalline cellulose (0.1% magnesium stearate), adhesion decreased with Increased tablet thickness or decreased tablet diameter (constant thickness) ac constant compression pressure Simultaneous measurement of ejection forces revealed that differences in true lubricant efficiency did not necessarily reflect differences in adhesion. The ability to distinquish differences in adhesion offers promise in assisting in the rational design of tablet formulations.     

Effect of Some Excipjents and Compression Pressure on the Adhesion of Aqueous-Based Hydroxypropyl Methylcellulose Film Coatings to Tablet Surface

The adhesion between aqueous-based hydroxypropyl methylcellulose (HPMC) films and tablet surface was evaluated using a Lloyd LRX materials testing machine. Special attention was paid to the effects of compression pressure and the excipients (microcrystalline cellulose, lactose and a commercial combination of lactose and cellulose (Cellactose^R)) on the adhesion properties of the film.

The adhesion of HPMC films was the lowest for the tablets containing lactose as a diluent and the highest for the tablets containing microcrystalline cellulose. The adhesion to Cellactose^R-based tablets increased with increasing compression pressure. With microcrystalline cellulose (MCC) and lactose, the effect of compression pressure on film adhesion was not so clear. The increase in concentration of a hydrophopic lubricant, magnesium stearate, decreased the adhesion between the films and tablets cores. The greatest decrease was observed with the MCC tablets.

Furthermore the results showed that, the film coating increased clearly the mechanical strength of the tablets, depending on the excipient, the compression pressure and amount of magnesium stearate.     

Effect of Some Excipjents and Compression Pressure on the Adhesion of Aqueous-Based Hydroxypropyl Methylcellulose Film Coatings to Tablet Surface

Abstract

The adhesion between aqueous-based hydroxypropyl methylcellulose (HPMC) films and tablet surface was evaluated using a Lloyd LRX materials testing machine. Special attention was paid to the effects of compression pressure and the excipients (microcrystalline cellulose, lactose and a commercial combination of lactose and cellulose (Cellactose^R)) on the adhesion properties of the film.

The adhesion of HPMC films was the lowest for the tablets containing lactose as a diluent and the highest for the tablets containing microcrystalline cellulose. The adhesion to Cellactose^R-based tablets increased with increasing compression pressure. With microcrystalline cellulose (MCC) and lactose, the effect of compression pressure on film adhesion was not so clear. The increase in concentration of a hydrophopic lubricant, magnesium stearate, decreased the adhesion between the films and tablets cores. The greatest decrease was observed with the MCC tablets.

Furthermore the results showed that, the film coating increased clearly the mechanical strength of the tablets, depending on the excipient, the compression pressure and amount of magnesium stearate.     

Effect of Lubricants on Tensile Strengths of Tablets

The effect of concentration of lubricant on the axial and radial tensile strengths of tablets was determined for four directly compressible pharmaceutical materials: anhydrous lactose, aspirin, microcrystalline cellulose, and dibasic calcium phosphate dihydrate. The lubricants investigated were: hydrogenated vegetable oil, magnesium stearate, polyethylene glycol 4000, stearic acid, and talc. For plastic materials the tensile strengths were reduced as the concentration of the lubricant was increased. For brittle material the tensile strength was not changed significantly as the concentration of lubricant was increased.     

Press chamber coating as external lubrication for high speed rotary presses: lubricant spray rate optimization

Lubrication of the tooling (punches and dies) is necessary to produce tablets. The most commonly used lubricant is magnesium stearate. Adding and blending magnesium stearate to the tablet mass often has negative effects on the properties of the compressed tablets (e.g., decreasing the tensile strength of the tablet). To avoid these negative effects, external lubrication systems were developed. This study investigated the functionality and the influence of a new press chamber coating system called the PKB II. The major difference between the PKB II and previous systems is its ability to spray a mixture of powdered magnesium stearate and air directly onto the punches and dies which was determined to allow the running of the rotor at higher speeds. The data showed a clear correlation between the spray rate of the lubricant and the concentration of the magnesium stearate per tablet. The PKB II was designed to allow for adjustments, in order to optimize the spray rate, by using the ejection force. The concentration of magnesium stearate was reduced to approximately 0.04% per tablet, using the PKB II. Additionally, the most common negative effects, such as the decrease in tablet tensile strength, were avoided by using this system.     

Press Chamber Coating as External Lubrication for High Speed Rotary Presses: Lubricant Spray Rate Optimization

ABSTRACT

Lubrication of the tooling (punches and dies) is necessary to produce tablets. The most commonly used lubricant is magnesium stearate. Adding and blending magnesium stearate to the tablet mass often has negative effects on the properties of the compressed tablets (e.g., decreasing the tensile strength of the tablet). To avoid these negative effects, external lubrication systems were developed. This study investigated the functionality and the influence of a new press chamber coating system called the PKB II. The major difference between the PKB II and previous systems is its ability to spray a mixture of powdered magnesium stearate and air directly onto the punches and dies which was determined to allow the running of the rotor at higher speeds. The data showed a clear correlation between the spray rate of the lubricant and the concentration of the magnesium stearate per tablet. The PKB II was designed to allow for adjustments, in order to optimize the spray rate, by using the ejection force. The concentration of magnesium stearate was reduced to approximately 0.04% per tablet, using the PKB II. Additionally, the most common negative effects, such as the decrease in tablet tensile strength, were avoided by using this system.     

Effects of Lubricant Level, Method of Mixing, and Duration of Mixing on a Controlled-Release Matrix Tablet Containing Hydroxypropyl Methylcellulose

The effects of the lubricant magnesium stearate at different concentrations, mixing shear rates, and mixing times on the tablet properties and drug dissolution from controlled-release matrix tablets containing hydroxypropyl methylcellulose 2208, USP (METHOCEL® K4M Premium) have been studied. Diphenhydramine HCl and hydrochlorothiazide were chosen as the model drugs. Spray-dried hydrous lactose (Fast Flo Lactose-316®) and anhydrous dibasic calcium phosphate (A-TAB®) were chosen as the model excipient/fillers. The impact of magnesium stearate on the mechanical strength of tablets appeared to be dependent on the bonding mechanism of the components of the powder mix. Tablets containing A-TAB, which compacts via a brittle fracture mechanism, were harder and had significantly better friability patterns than those prepared using Fast Flo Lactose-316. The compaction of Fast Flo Lactose-316 appears to be a combination of brittle fracture and plastic deformation. Mixes containing lower levels of lubricant (0.2%) generated tablets that had higher crushing strengths than those with higher lubricant levels (2.0%). Drug release was impacted to the greatest extent by the solubility of the drug and excipient/filler but was only slightly affected by the level of magnesium stearate and duration of mixing.     

Effects of Lubricant Level,Method of Mixing,and Duration of Mixing on a Controlled-Release Matrix Tablet Containing Hydroxypropyl Methylcellulose

Abstract

The effects of the lubricant magnesium stearate at different concentrations, mixing shear rates, and mixing times on the tablet properties and drug dissolution from controlled-release matrix tablets containing hydroxypropyl methylcellulose 2208, USP (METHOCEL® K4M Premium) have been studied. Diphenhydramine HCl and hydrochlorothiazide were chosen as the model drugs. Spray-dried hydrous lactose (Fast Flo Lactose-316®) and anhydrous dibasic calcium phosphate (A-TAB®) were chosen as the model excipient/fillers. The impact of magnesium stearate on the mechanical strength of tablets appeared to be dependent on the bonding mechanism of the components of the powder mix. Tablets containing A-TAB, which compacts via a brittle fracture mechanism, were harder and had significantly better friability patterns than those prepared using Fast Flo Lactose-316. The compaction of Fast Flo Lactose-316 appears to be a combination of brittle fracture and plastic deformation. Mixes containing lower levels of lubricant (0.2%) generated tablets that had higher crushing strengths than those with higher lubricant levels (2.0%). Drug release was impacted to the greatest extent by the solubility of the drug and excipient/filler but was only slightly affected by the level of magnesium stearate and duration of mixing.     

Spray-Dried Rice Starch: Comparative Evaluation of Direct Compression Fillers

Spray-dried rice starch (SDRS), microcrystalline cellulose (MCC), lactose (L), pregelatinized starch (PS), and dibasic calcium phosphate (DCP) were studied for their flow behaviors and tableting properties. Both flow rate and percent compressibility values indicated that SDRS exhibited excellent flowability. The increase in magnesium stearate content reduced the hardness of MCC and SDRS tablets; however, general tablet properties were still acceptable while the PS tablets were unsatisfactory at high lubricant concentrations. The hardness of L or DCP tablets was not affected by the lubricant. The disintegration of L tablets was prolonged with the increased lubricant concentration while that of PS tablets seemed to be decreased due to softened tablets. The disintegration times of MCC and SDRS tablets seemed to be independent of the lubricant added. With respect to the dissolution, SDRS-based tablets offered fast and complete release of the drug regardless of its solubility. SDRS, L, and DCP exhibited comparable carrying capacity for ascorbic acid. The best dilution potential was obtained with MCC while the worst was obtained with PS.     

Aspects of the Lubrication Requirements for an Automatic Capsule Filling Machine

Aspects of the lubrication requirements for an automatic capsule filling machine, instrumented to monitor compression and ejection forces, were studied under various filling conditions. Three common capsule fillers (compressible starch, micro-crystalline cellulose, and anhydrous lactose) were filled into No. 1 gelatin capsules. Two main sets of runs were made. The first set was designed to study the influence of powder bed height, piston height and compression force on the ejection forces generated during the filling process. The second set was aimed at comparing lubricant type and levels. It was shown that the ejection force is increased by increasing the powder bed height, piston height and compression force. Compressible starch and micro-crystalline cellulose required relatively low levels of magnesium stearate as compared to anhydrous lactose. The performance of stearic acid and especially magnesium lauryl sulfate compared favorably with magnesium stearate in compressible starch.     

Spray-Dried Rice Starch: Comparative Evaluation of Direct Compression Fillers

Abstract

Spray-dried rice starch (SDRS), microcrystalline cellulose (MCC), lactose (L), pregelatinized starch (PS), and dibasic calcium phosphate (DCP) were studied for their flow behaviors and tableting properties. Both flow rate and percent compressibility values indicated that SDRS exhibited excellent flowability. The increase in magnesium stearate content reduced the hardness of MCC and SDRS tablets; however, general tablet properties were still acceptable while the PS tablets were unsatisfactory at high lubricant concentrations. The hardness of L or DCP tablets was not affected by the lubricant. The disintegration of L tablets was prolonged with the increased lubricant concentration while that of PS tablets seemed to be decreased due to softened tablets. The disintegration times of MCC and SDRS tablets seemed to be independent of the lubricant added. With respect to the dissolution, SDRS-based tablets offered fast and complete release of the drug regardless of its solubility. SDRS, L, and DCP exhibited comparable carrying capacity for ascorbic acid. The best dilution potential was obtained with MCC while the worst was obtained with PS.     

A Feasibility study for the Development of a Prospective Compaction Functionality test and the Establishment of a Compaction data BANK

The feasibility for the development of a standard compaction functionality testing method, which is capable of comparing the relative tabletability features of different materials and different lots of the same material with high sensitivity, was tested using an Integrated Compaction Research System. The following factors were optimized: tablet weight, lubrication, tooling, punch displacement profile, pressure range, as well as other pre-, during and post-compaction parameters. The optimized test conditions were found to be as follows: the amount of material to be compacted was calculated to produce a compact with a true volume of 0.25ml; internal lubricant with magnesium stearate at a concentration of 0.5%; standard 10.3mm, flat-faced, round BB tooling; constant punch velocities of 100mm/s and 300mm/s; and a pressure range of 25 to 550MPa. Several model powders which included microcrystalline cellulose, dicalcium phosphate dihydrate, calcium sulfate, dextrates, lactose anhydrous, and spray dried lactose were tested. Using the data generated in this work, the establishment of a compaction data bank that can be utilized as a reference source for tablet formulation studies was also found to be feasible.     

Glidants and Lubricant Properties of Several Types of Talcs

Glidant and lubricant efficiencies of a number of different types of talcs were evaluated. The in vitro properties of tablets lubricated with talcs were compared to those lubricated with magnesium stearate. Talc lubricated tablets showed superior in vitro properties compared to magnesium stearate lubricated tablets. Different sources of talcs showed significant differences in glidant and lubricant efficiencies.     

A Feasibility study for the Development of a Prospective Compaction Functionality test and the Establishment of a Compaction data BANK

Abstract

The feasibility for the development of a standard compaction functionality testing method, which is capable of comparing the relative tabletability features of different materials and different lots of the same material with high sensitivity, was tested using an Integrated Compaction Research System. The following factors were optimized: tablet weight, lubrication, tooling, punch displacement profile, pressure range, as well as other pre-, during and post-compaction parameters. The optimized test conditions were found to be as follows: the amount of material to be compacted was calculated to produce a compact with a true volume of 0.25ml; internal lubricant with magnesium stearate at a concentration of 0.5%; standard 10.3mm, flat-faced, round BB tooling; constant punch velocities of 100mm/s and 300mm/s; and a pressure range of 25 to 550MPa. Several model powders which included microcrystalline cellulose, dicalcium phosphate dihydrate, calcium sulfate, dextrates, lactose anhydrous, and spray dried lactose were tested. Using the data generated in this work, the establishment of a compaction data bank that can be utilized as a reference source for tablet formulation studies was also found to be feasible.     

The Effect of the Variability in the Physical and Chemical Properties of Magnesium Stearate on the Properties of Compressed Tablets

Abstract

A series of magnesium stearate samples, supplied by foreign and domestic manufacturers, were characterized by their physical and chemical properties. The results Indicated that the samples differed significantly with respect to chemical purity, particle size and surface area. The properties of magnesium stearate lots, manufactured by the same company, were very similar. Whatever variation that was seen was principally due to different suppliers.

Microcrystall1ne cellulose tablet formulations were prepared and evaluated using samples of magnesium stearate obtained from 16 sources. Differences 1n tablet quality were observed 1n regard to bulk volume of the blends, tablet tensile strength, and tablet friability. The data revealed that the smaller particle sized magnesium stearate samples (2.4–7.0 μm), with a large surface area (10.6–14.8 m2/g), had the most detrimental effects on the physical properties of mlcrocrystalHne cellulose tablets. Regression analysis and modeling was used to define quantltate, and predict the effects of magnesium stearate source variation on the physical properties of mlcrocrystalHne cellulose blends and compressed tablets.     

The Effect of the Variability in the Physical and Chemical Properties of Magnesium Stearate on the Properties of Compressed Tablets

A series of magnesium stearate samples, supplied by foreign and domestic manufacturers, were characterized by their physical and chemical properties. The results Indicated that the samples differed significantly with respect to chemical purity, particle size and surface area. The properties of magnesium stearate lots, manufactured by the same company, were very similar. Whatever variation that was seen was principally due to different suppliers.

Microcrystall1ne cellulose tablet formulations were prepared and evaluated using samples of magnesium stearate obtained from 16 sources. Differences 1n tablet quality were observed 1n regard to bulk volume of the blends, tablet tensile strength, and tablet friability. The data revealed that the smaller particle sized magnesium stearate samples (2.4-7.0 μm), with a large surface area (10.6-14.8 m2/g), had the most detrimental effects on the physical properties of mlcrocrystalHne cellulose tablets. Regression analysis and modeling was used to define quantltate, and predict the effects of magnesium stearate source variation on the physical properties of mlcrocrystalHne cellulose blends and compressed tablets.     

Glidants and Lubricant Properties of Several Types of Talcs

Abstract

Glidant and lubricant efficiencies of a number of different types of talcs were evaluated. The in vitro properties of tablets lubricated with talcs were compared to those lubricated with magnesium stearate. Talc lubricated tablets showed superior in vitro properties compared to magnesium stearate lubricated tablets. Different sources of talcs showed significant differences in glidant and lubricant efficiencies.     

Dissolution properties of direcet compression tablets containing an agglomerated cellulose powder

In previous studies a novel agglomerated cellulose powder was shown to own advantageous properties for direct compression. Due to the favourable particle and powder properties this material has good binding and disintegration ability in direct compression tablets. In this study the dissolution properties of direct compression tablets containing the agglomerated cellulose powder as a fillerbinder were evaluated. Especially the effect of the amount of cellulose, the porosity of tablets, the solubility of drug material and the amount and the amount and mixing method of lubricant, magnesium stearate were studied.

Tablets containing different amounts of cellulose with dicalcium phosphate as a filler and 10 wt % of water soluble sodium tolmetin as a drug were compressed at a constant pressure of 150 MPa. The breaking strength of tablets increased with increasing amounts of agglomerated cellulose powder. However, the dissolution of drug accelerated up to cellulose amount of 50 wt %. This was due to the ability of the agglomerated cellulose powder to enhance the water penetration into powder compact and the loosening of tablet structure, i.e. formation of cracks.

Tablets containing 20 wt % of cellulose material and 10 wt % of drug material were compressed to different porosities. Tablet porosity had no effect on dissolution of poorly water soluble tolfenamic acid. Also the dissolution of water soluble sodium tolmetin was only slightly affected by the porosity of tablets. This supports the suggested disintegrant mechanism of the agglomerated cellulose powder. The expansion of cellulose agglomerates, which have been deformed, under compression, is widely responsible for the disintegration of the tablets. An increase in the amount as well as in the mixing intensity of magncsium stearate decreased the dissolution of sodium tolmetin from tablets containing 20 wt % of agglomerated cellulose. However, the intrinsic wetting and dissolution phenomens were practically unchanged when the amount of magnesium stearate was below 2 wt %. Thus, the retardation of drug dissolution was acceptable at low lubricant concentrations.

The properties of tablets containing the agglomerated cellulose were compared to those containing microcrystalline cellulose. In all cases tablets containing the agglomerated cellulose powder liberated drug clearly faster and more properly than corresponding microcrystalline cellulose tablets.     

Coated pelletized dosage form: Effect of compaction on drug release

Abstract

The goal of this study was to investigate the effect of compaction of a coated pelletized dosage form on drug release. Three sizes of microcrystalline cellulose and hydrous lactose pellets containing 4% chlorpheniramine maleate (CPM) were manufactured using a rotogranulator (Glatt GPCG-1). Pellets having mesh cuts of: 590–840 μm (20/30 mesh); 420–590 μm (30/40 mesh); and 250–420 μm (40/60 mesh) were then coated with an aqueous ethylcellulose pseudolatex dispersion plasticized with 24% dibutyl sebacate (DBS). Percent weight gains were 25, 30 and 35% for the 20/30, 30/40 and 40/60 mesh pellets, respectively. Coated pellets were blended with 39.3% by weight excipients, then mixtures lubricated and compacted using a Korsch PH106 instrumented rotary press set at 5 kN and 20 rpm (0.30 s contact time). Magnesium stearate was used as the lubricant at a 0.7% level. Excipients used were microcrystalline cellulose, spray dried lactose, pregelatinized starch, dicalcium phosphate, spray dried sorbitol, polyethylene glycol 8000 powder and compressible sugar. Results indicated this coating to be suitable for the controlled release of CPM from small pellets (250–840 μm). However, films did not have the appropriate mechanical properties to withstand compaction stress without rupturing, regardless of the pellets particle size and excipients used. After compaction, depending on pellet size, between 65–100% CPM was released after one hour as opposed to 10–30% for the non-compacted material. The controlled release properties of the pellets were therefore lost during the process.