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

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.     

Influence of Tableting Forces and Lubricant Concentration on the Adhesion Strength in Complex Layer Tablets

The strength of adhesion in complex two-layer tablets is assessed using statistical methods with respect to the applied tableting forces for the first layer and for applying the second layer on the first, as well as regarding the fraction of the lubricant. These results, obtained on a single-punch tablet press, are compared with the results for three-layer tablets produced on a rotary press at production scale. The strongest negative influence on adhesion strength was exerted by the amount of lubricant in the central layer. As expected, compression forces for central-layer tableting also had a negative effect, whereas the compression forces for complex layer tableting exerted a positive effect on layer adhesion. The validity of the derived model equation was proved by experiments: It was shown that the adhesion strength in complex layer tablets produced in production scale can be predicted from laboratory-scale experiments. This makes optimization of the formulation and parameter settings at an early stage of development possible.     

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.     

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.     

Fine-Particle Ethylcellulose as a Tablet Binder in Direct Compression,Immediate-Release Tablets

Ethylcellulose has traditionally been used in tablets as a binder in an alcohol solution form. In the present study, fine-particle ethylcellulose (FPEC) was used as a binder to manufacture immediate-release tablets by the direct compression technique. The binding potential of FPEC is compared to that of commercially available coarse-particle ethylcellulose at the same viscosity grade and to that of hydrophilic binders. The compression force setting was kept constant for all batches. The concentration of the binder was varied from 5% to 25%. Acetaminophen was used as a model drug because capping is a problem frequently observed during high-speed compaction and further processing of acetaminophen tablets. In this study, there would be an increase in the contact area with FPEC and hence greater bond formation. This greater bond formation should be able to reduce the problem of capping in tablets containing highly elastic materials such as acetaminophen. Tablets were evaluated based on the following tests: weight variation, extent of capping, hardness, friability, disintegration, and dissolution. Based on the results of these tests, FPEC proved to be an effective binder for directly compressed acetaminophen tablets. The 10% and 15% formulations of FPEC passed all the tests and also produced the hardest tablets.     

Fine-Particle Ethylcellulose as a Tablet Binder in Direct Compression, Immediate-Release Tablets

Ethylcellulose has traditionally been used in tablets as a binder in an alcohol solution form. In the present study, fine-particle ethylcellulose (FPEC) was used as a binder to manufacture immediate-release tablets by the direct compression technique. The binding potential of FPEC is compared to that of commercially available coarse-particle ethylcellulose at the same viscosity grade and to that of hydrophilic binders. The compression force setting was kept constant for all batches. The concentration of the binder was varied from 5% to 25%. Acetaminophen was used as a model drug because capping is a problem frequently observed during high-speed compaction and further processing of acetaminophen tablets. In this study, there would be an increase in the contact area with FPEC and hence greater bond formation. This greater bond formation should be able to reduce the problem of capping in tablets containing highly elastic materials such as acetaminophen. Tablets were evaluated based on the following tests: weight variation, extent of capping, hardness, friability, disintegration, and dissolution. Based on the results of these tests, FPEC proved to be an effective binder for directly compressed acetaminophen tablets. The 10% and 15% formulations of FPEC passed all the tests and also produced the hardest tablets.     

Influence of Pigment Concentration and Particle Size on Adhesion of an Acrylic Resin Copolymer to Tablet Compacts

The effects of the particle size and the concentration of pigments in aqueous polymeric dispersions on the adhesive properties of an acrylic resin copolymer were investigated. Aqueous polymeric dispersions containing up to 20% (v/v) pigment were coated onto hydrophilic and hydrophobic tablet compacts, and polymer adhesion was assessed using a novel butt adhesion technique. An inverse relationship was found between the particle size of the pigment present in the aqueous polymeric dispersion and film-tablet adhesion. As the particle size of the pigment increased, the adhesive strength of the polymer to the tablet compact decreased. Increased concentrations of the opacifying agent titanium dioxide in the acrylic dispersion resulted in stronger film-tablet adhesion. No clear relationship could be established between the wettability of the tablet compact by the pigmented polymeric dispersion and the strength of film-tablet adhesion. The hydrophobicity of the tablet compact was found to affect the glass transition temperature of the polymeric film to a greater extent than the particle size, morphology, or concentration of the pigment incorporated into the acrylic dispersion.     

Force-Time-Curves of a Modern Rotary Tablet Machine I. Evaluation Techniques and Characterization of Deformation Behaviour of Pharmaceutical Substances

According to the geometry of punch heads and the interdependent punch movements force-time-curves of a rotary-tablet press are divided into periods by the aid of the signal of an inductive sensor. The decrease of compaction load in the interval of the flat punch top is mainly due to plastic flow of the compressed substances. Brittle or plastic deformation behaviour is easily distinguished and quantified by the combination of a standard press and a highly advanced data acquisition and off-line software evaluation.

Additionally it is shown that there is no need to use a complex equipment for displacement measurement to gather reliable data on compaction mechanisms. Even if the machine deformation is considered, calculated displacement data may surpass measured data in precision.     

Force-Time-Curves of a Modern Rotary Tablet Machine I. Evaluation Techniques and Characterization of Deformation Behaviour of Pharmaceutical Substances

Abstract

According to the geometry of punch heads and the interdependent punch movements force-time-curves of a rotary-tablet press are divided into periods by the aid of the signal of an inductive sensor. The decrease of compaction load in the interval of the flat punch top is mainly due to plastic flow of the compressed substances. Brittle or plastic deformation behaviour is easily distinguished and quantified by the combination of a standard press and a highly advanced data acquisition and off-line software evaluation.

Additionally it is shown that there is no need to use a complex equipment for displacement measurement to gather reliable data on compaction mechanisms. Even if the machine deformation is considered, calculated displacement data may surpass measured data in precision.     

Optimization of Disintegration Time and Crushing Strength of a Tablet Formulation

Abstract

In an experiment with a factorial design, the following aspects were scrutinized: the impact on disintegration time and crushing strength caused by the loss-on-drying of the granulation; the granule-size distribution; the lubricant concentration; the compression force; and the pre-compression. Both with regard to disintegration time and crushing strength, these factors were found to have a significant influence: the loss-on-drying of the granulation; the fraction less than 0.150 mm; the concentration of magnesium stearate; and the compression force. A reduction of the tablet disintegration time was obtained by means of an increase of the granulation moisture; by an increase of the fine fraction; or by a reduction of the lubricant concentration or the compression force. The tablet crushing strength was increased by reducing the deviation of the granulation loss-on-drying from approximately 4.6 %; by a reduction of the fine fraction; by decreasing the lubricant concentration; or by increasing the compression force. The fraction larger than 0.300 mm had no significant influence; nor did the pre-compression. Further, there were no significant interactions.

By means of superimposing contour plots of disintegration time and crushing strength, a region was obtained where the requirements of disintegration time and crushing strength could be satisfied by controlling the processing variables.     

Optimization of Disintegration Time and Crushing Strength of a Tablet Formulation

In an experiment with a factorial design, the following aspects were scrutinized: the impact on disintegration time and crushing strength caused by the loss-on-drying of the granulation; the granule-size distribution; the lubricant concentration; the compression force; and the pre-compression. Both with regard to disintegration time and crushing strength, these factors were found to have a significant influence: the loss-on-drying of the granulation; the fraction less than 0.150 mm; the concentration of magnesium stearate; and the compression force. A reduction of the tablet disintegration time was obtained by means of an increase of the granulation moisture; by an increase of the fine fraction; or by a reduction of the lubricant concentration or the compression force. The tablet crushing strength was increased by reducing the deviation of the granulation loss-on-drying from approximately 4.6 %; by a reduction of the fine fraction; by decreasing the lubricant concentration; or by increasing the compression force. The fraction larger than 0.300 mm had no significant influence; nor did the pre-compression. Further, there were no significant interactions.

By means of superimposing contour plots of disintegration time and crushing strength, a region was obtained where the requirements of disintegration time and crushing strength could be satisfied by controlling the processing variables.     

A Comparison of Dissolution from Commercial Tablets and from Capsules Containing a Powdered Tablet

Abstract

In clinical trials it may be necessary to convert a commercial tablet to a capsule so that the identity of each drug being tested remains unknown until the trial is completed. This study shows that for six commercial tablets, after pulverization and encapsulation of the powder, the in vitro dissolution was faster for one product, slower for two products and essentially unchanged for three products.     

Studies of Furosemide Tablets II Influence of Wet-Mixing Time, Binder Volume and Batch Variation on Dissolution Rate

The effect of wet-mixing time and the volume of granulating solution on furosemide tablet quality and in vitro dissolution rate were studied. The wet-mixing time has shown an effect on the in vitro dissolution of furosemide tablet formulation. Small variations in wet-mixing time can be important and effective on the tablet dissolution. A decrease in the dissolution rate was observed when the time of wet-mixing increased.

Changes in the volume of granulating solution, when the amount of gelatin was constant, did not alter the tablet dissolution.

Moreover, the effect of batch variation on tablet formulation was also investigated. There was no significant differences in the dissolution of the different batch of furosemide bulk powder.     

A Comparison of Dissolution from Commercial Tablets and from Capsules Containing a Powdered Tablet

In clinical trials it may be necessary to convert a commercial tablet to a capsule so that the identity of each drug being tested remains unknown until the trial is completed. This study shows that for six commercial tablets, after pulverization and encapsulation of the powder, the in vitro dissolution was faster for one product, slower for two products and essentially unchanged for three products.     

Residence Time Distribution of Segregating Sand Particles in a Rotary Drum

Leaching, which is described as the extraction of soluble constituents from a solid by means of a solvent, is an important separation technique in the refining of precious metals from their matte. It is, therefore, important to investigate the extraction behavior of metals from the matte, which is the focus of this study. This study reports the influence of concentration of the solvent (ammonia), leaching temperature, leaching time, and pH on the recovery of nickel and copper from the matte. The elemental composition analysis of the matte indicated that it contains 23% copper, 37% nickel and 1.1% ferrous compound. The analysis also showed that the major mineral phases present in the matte were heazlewoodite (Ni₃S₂), chalcocite (Cu₂S), djurleite (Cu1.9S), and nickel alloy. The leaching parameters studied were concentration of ammonia (1.5, 2.0, 2.5, and 3.0 M), leaching time (0–270 min, at 15 min sampling interval), leaching temperatures (50°C, 60°C, and 70°C), and pH (9.3–11.2). The results obtained revealed that the recovery of nickel and copper from the matte was greatly influenced by the concentration of ammonia, leaching time, leaching temperature, and pH. It was established from this study that the highest dissolution of nickel and copper was obtained at 3 M and 2 M ammonia concentration, respectively. The results also revealed that a decrease in the pH of the solution resulted in a decrease in both nickel and copper recovery, with maximum leaching time of 270 min. It was observed that less than 50% of both nickel and copper was leachable due to the presence of metal alloys. The analyses of the results also showed that as the leaching temperature increased from 50°C to 60°C, the amount of nickel and copper that was recovered from the matte significantly increased. However, there was reduction in the amount of nickel and copper recovered from the matte as the temperature was increased from 60°C to 70°C, due to loss of ammonia by evaporation. The shrinking core model was used to explain the behavior of the recovery of these metals at different temperatures, and both metals were found to be favored by diffusion controlled reaction.     

Degradation Kinetics of Thiamine Hydrochloride in Directly Compressed Tablets II: Reliability of Accelerated Stability Testing for Evaluating Tablet Formulations

Abstract

Directly compressed thiamine hydrochloride tablets formulated with single or binary blend of vehicles were used in this investigation. The change in the physical characteristics of vitamin tablets stored under different relative humidity conditions was statistically assessed and scored by relative ranking. Although Emcompress is known to accelerate drug decomposition (1,2) the results obtained with tablets formulated with this vehicle alone or in combination with other vehicles failed to show that the use of this vehicle may give rise to any discernible changes in the physical characteristics of the tablets. Although formulations containing Celutab as the vehicle are chemically stable (2) the tablets compressed with this vehicle showed a high degree of change in physical characteristics. The results obtained in this study indicate that Avicel alone or a blend of Avicel with either Celutab or Anhydrous lactose are suitable vehicles for the manufacture of thiamine hydrochloride tablets of high stability characteristics.     

A Study of the Effects of Sucrose Concentration,Lacquer Concentration and Coating Time on the Formulation of Stable and Effective Carbenicillin Indanyl Sodium Microcapsules

Abstract

Carbenicillin indanyl sodium, commonly known as Geocillin (GC), is an orally effective derivative of carbenicillin employed in the treatment of gram negative infections of the urinary tract. GC exhibits an extremely bitter taste which affects patient compliance upon oral dosing (1). A novel coating approach allows Geocillin to be prepared as a suspension for oral administration. GC is available only as a tablet.

Eudragit E100^R [EE] is a tasteless, acid soluble cationic polymer. Encapsulation of GC with [EE] inhibited its release in the mouth, thus overcoming its bitter taste. Dissolution studies were carried out in simulated gastric fluid and simulated intestinal fluid. Three factors, viz. sucrose concentration, lacquer concentration and coating time were evaluated to arrive at an optimally acceptable formulation.

The formulation containing GC and sucrose in the ratio of 1:3, suspension coated using a 5% w/w lacquer solution for 40 mins. yielded taste free microcapsules with optimal release characteristics.