Evaluation of the effects of khaya gum on the mechanical and release properties of paracetamol tablets

A study of the comparative effects of khaya gum and two standard binding agents-polyvinylpyrrolidone (PVP) and gelatin--on crushing strength and friability, and the disintegration and dissolution characteristics of paracetamol tablets was made. The crushing strength-friability ratio (CSFR), the disintegration times, D, and the dissolution times t50, t90, and t1 (derived from the equation of Noyes and Whitney), all increased with an increase in binder concentration; however, the dissolution rate constants, k1 and k2, decreased. The ranking for the values of CSFR for tablets containing the different binders was PVP > gelatin > khaya gum. The ranking for D and the dissolution times was gelatin > khaya gum > PVP, whereas the ranking for the dissolution rate constants was PVP > khaya gum > gelatin. There were significant linear correlations between CSFR, D, t50, t90, and t1 for the tablets. There were also significant correlations between k1 and D, t50, t90, and t1, and between k2 and t90. The results suggest that khaya gum could be useful as an alternative binding agent to produce tablets with particular mechanical strength and drug release profiles.     

Investigating the Fundamental Effects of Binders on Pharmaceutical Tablet Performance

For solid dosage forms, a better understanding of the fundamental properties of the binders helps in developing better formulations and products. The objective of this study was to determine the effects of binder toughness and plastic flow on tablet hardness, friability, and capping. The characteristic of binder toughness was determined, and the correlation between the ejection force of the tablet and the toughness of the binder was established. Evaluation was conducted using acetaminophen tablets with different kinds of binders (i.e., hydroxypropylcellulose, methylcellulose [MC], povidone [PVP], starch, etc.). A rotary tablet press was used for tableting at three different speeds. The properties of binders and acetaminophen tablets were determined using a diametral compression test. The toughness was measured as the curve of the area under the load versus deflection. The microbehavior of these binders was also studied. The acetaminophen tablets with the binders were subjected to predetermined loads and then examined under a scanning electron microscope. The tablets that contained hydroxypropylcellulose as a binder showed the highest toughness and had the lowest ejection force. The ejection force of tablets decreased with increasing concentrations of hydroxypropylcellulose in the dosage forms. The tablets that contained other binders failed by capping and random cracking in the middle. These results show that hydroxypropylcellulose, a thermoplastic polymer, provides the best physical characteristics for the tablets. This effect could help in improving tablet manufacturing conditions (e.g., compression force and speed).     

Effects of Binders and Moisture Content on the Disintegration, Hardness and Friability of Paracetamol and Orphenadrine Citrate Tablets

The effects of binders and moisture content on the disintegration time, friability and hardness of paracetamol and orphenadrine citrate tablets at different storage conditions were investigated. These parameters were determined after one, four and sixteen weeks of storage

The use of starch, ethocel or CMC Na as binders gave unsatisfactory tablets because of their high friability. Unacceptably high disintegration times were obtained, particularly at higher storage temperatures when PVP was used. Capping and yellow spotting observed in gelatin formulations makes this binder unsuitable for use. Methocel granulations yielded satisfactory tablets with acceptable disintegration time, hardness and friability and were unaffected by storage at different conditions of temperature and humidity     

Effects of Binders and Moisture Content on the Disintegration,Hardness and Friability of Paracetamol and Orphenadrine Citrate Tablets

Abstract

The effects of binders and moisture content on the disintegration time, friability and hardness of paracetamol and orphenadrine citrate tablets at different storage conditions were investigated. These parameters were determined after one, four and sixteen weeks of storage

The use of starch, ethocel or CMC Na as binders gave unsatisfactory tablets because of their high friability. Unacceptably high disintegration times were obtained, particularly at higher storage temperatures when PVP was used. Capping and yellow spotting observed in gelatin formulations makes this binder unsuitable for use. Methocel granulations yielded satisfactory tablets with acceptable disintegration time, hardness and friability and were unaffected by storage at different conditions of temperature and humidity     

Investigating the Fundamental Effects of Binders on Pharmaceutical Tablet Performance

For solid dosage forms, a better understanding of the fundamental properties of the binders helps in developing better formulations and products. The objective of this study was to determine the effects of binder toughness and plastic flow on tablet hardness, friability, and capping. The characteristic of binder toughness was determined, and the correlation between the ejection force of the tablet and the toughness of the binder was established. Evaluation was conducted using acetaminophen tablets with different kinds of binders (i.e., hydroxypropylcellulose, methylcellulose [MC], povidone [PVP], starch, etc.). A rotary tablet press was used for tableting at three different speeds. The properties of binders and acetaminophen tablets were determined using a diametral compression test. The toughness was measured as the curve of the area under the load versus deflection. The microbehavior of these binders was also studied. The acetaminophen tablets with the binders were subjected to predetermined loads and then examined under a scanning electron microscope. The tablets that contained hydroxypropylcellulose as a binder showed the highest toughness and had the lowest ejection force. The ejection force of tablets decreased with increasing concentrations of hydroxypropylcellulose in the dosage forms. The tablets that contained other binders failed by capping and random cracking in the middle. These results show that hydroxypropylcellulose, a thermoplastic polymer, provides the best physical characteristics for the tablets. This effect could help in improving tablet manufacturing conditions (e.g., compression force and speed).     

Prelimnaky Evaluation of Cissus Root Gum as a Binder in Sodium Salicylate Tablet Formulations

Abstract

Cissus root gum was processed and evaluated as a binder in lactose-based tablets each containing 100 mg of sodium salicylate as the active ingredient. Acacia binder was used as basis for comparison. Tablet hardness, friability, disintegration time and dissolution rate were the parameters investigated. The cissus gum gave hard and non-friable tablets at 1 - 3% w/w concentration of the tablet formula. Tablets containing above 2% w/w of the cissus gum gave high disintegration time values and the pattern of dissolution of the incorporated drug suggests that the gum may be useful in prolonged release tablet formulations. No significant changes in the tablet properties was observed after storage at 30°C for 16 weeks.     

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.     

The effect of wax on compaction of microcrystalline cellulose beads made by extrusion and spheronization

The effect of wax on the deformation behavior and compression characteristics of microcrystalline cellulose (Avicel PH-101) and acetaminophen (APAP) beads is described. Beads of Avicel PH-101 and APAP formulations were prepared using extrusion and spheronization technology. A waxy material, glyceryl behenate, N.F. (Compritol), was added to the formulations in amounts ranging from 10% to 70% of total solid weight. Beads with a selected particle size range of 16-30 mesh were compressed with an instrumented single punch Manesty F press utilizing a 7/16-in. flat-faced tooling set. Compaction profiles were generated for the tablets to evaluate the effect of wax on the densification of beads containing wax. Beads made without wax (the control formulation) required greater compression forces to form cohesive tablets. As the amount of wax in the bead formulation was increased, the beads become more plastic and compressible. The Heckel equation which relates densification to compression pressure was used to evaluate the deformation mechanisms of the bead formulations. The analysis shows that as the level of wax in the bead formulation is increased, the yield pressure decreases, indicating that the beads densify by a plastic deformation mechanism.     

Effectiveness of Binders in Wet Granulation: A Comparison Using Model Formulations of Different Tabletability

Based on an analysis of model granulates and tablets, a comparison was made of the effectiveness of the binders PVP K30 PH, Cellulose HP-M 603, Lycatab DSH, Lycatab PGS, and L-HPC (type LH 11). A high shear mixer was used to prepare two model granulates (placebo and paracetamol) under processing conditions which were, as far as possible, comparable. The binders were added as proportions of 2%, 6%, and 10%. Water was used as the granulating liquid. The properties of the placebo granulates (particle size distribution, bulk and tapped density, granule strength, flow properties), and those of the tablets (crushing strength, friability) prepared from these granulates under different compaction forces, were generally good. However, with PVP, Cellulose HP-M603, and Lycatab, the disintegration time of the tablets did not meet pharmacopoeial requirements even though a “disintegrant” was used in the “outer phase.” The paracetamol formulations were prime examples of high-dose drug substances with particularly poor granulating and tabletting properties, well suited to reveal differences between the binders. The paracetamol granulates were of higher friability and less flowability than the placebo granulates. The tablets tended to cap, friability was (with few exceptions) high, and disintegration times were long. In the preparation of model tablets containing paracetamol, PVP K30 PH (6%). and Cellulose HP-M 603 (6%) turn out to be the binders of choice with respect to crushing strength, but the disintegration times are too long. Lycatab PGS, Lycatab DSH, and L-HPC-LH 11 could not be used to produce paracetamol tablets that met the requirements.     

Granulations in a Fluidized-Bed: Effect of Binders and Their Concentrations on Granule Growth and Modeling the Relationship Between Granule Size and Binder Concentration

Lactose and mixture of lactose and microcrystalline cellulose (1:1) were granulated in a fluid-bed equipment using PVP, acacia and gelatin as binders. The effect of these binders, their concentrations, and volume of granulation liquid on granule growth and granule sue distribution was studied. It has been shown that individual binder and binder concentration affect granule growth and growth mechanism. Also, the volume of granulation liquid and part dissolution of excipients being granulated contribute significantly to the granule size and size distribution. On the basis of granule growth data, a mathematical relationship which relates granule size as a function of binder concentration is proposed. Granule growth constant for the binders is computed from the granule size against binder concentration data. The constant describes granule growth pattern, and is termed as binder coefficient, β. The numerical value of binder coefficient, which varies with the binder, indicates relative activity and effectiveness of each individual binder. A relationship between the binder coefficients is also established. This is shown to predict granule sue for a binder relative to another binder for the desired concentration. The validity and the applicability of the proposed relationship was tested on the data obtained during present investigations as well as on data reported by other authors.     

Tabletability of Maltodextrins and Acetaminophen Mixtures

Tabletability of five types of maltodextrin, a filler/binder excipient, was studied by testing their loading potentials with acetaminophen. The formulations consisted of excipient and acetaminophen at five different ratios and magnesium stearate at a 0.5% concentration. These mixtures were compacted employing an Integrated Compaction Research System at a constant punch velocity of 100 mm/sec. under varying applied pressures from 50 to 450 MPa. Compaction data were evaluated using the total work of compaction vs applied pressure plots whilst the post-compaction tests included the measurements of crushing force, disintegration time, and friability of the resulting tablets. Both the energy involved during the compaction of a formulation and the crushing force values of the resulting tablets decreased as the amount of the maltodextrin in a formulation was reduced. Maltodextrins exhibited adequate binding potential at acetaminophen drug loading levels of only up to twenty-five percent. The disintegration times of the tablets containing maltodextrins were generally prolonged and this was found to be due to the formation of a “gel” layer around the tablet which formed on immersion into water. The tabletability of maltodextrins were also compared to that of Fast-Flo lactose, and the compactability of these excipients were found to be similar.     

The effect of moisture on the physical characteristics of ranitidine hydrochloride tablets prepared by different binders and techniques

The effect of moisture on the physical properties of ranitidine hydrochloride tablets prepared by direct-compression and by wet-granulation method using PVP or EC as binders was studied. Tablets adsorped moisture at 50 and 75 % RH (relative humidity) but lost moisture at 30% RH. Except storage at 75% RH, however, tablet volumes did not change significantly during the test period. Moisture sorption caused a decrease in strength of tablets except low humidity (30% RH). Also, the disintegration time of tablets showed a decrease at all conditions except 30% RH. Furthermore, generally dissolution profiles of tablets prepared by direct-compression and by ethyl cellulose remained unchanged. Changes in the binder type in the tablet formulations changed the water uptake properties and also the physical properties of tablets. Directly-compressed tablets were much susceptible to change caused by humidity than tablets prepared by wet-granulation.     

Effects of pigeon pea and plantain starches on the compressional, mechanical, and disintegration properties of paracetamol tablets

A study has been made of the effects of pigeon pea starch obtained from the plant Cajanus cajan (L) Millisp. (family Fabaceae) and plantain starch obtained from the unripe fruit of Musa paradisiaca L. (family Musaceae) on the compressional, mechanical, and disintegration properties of paracetamol tablets in comparison with official corn starch BP. Analysis of compressional properties was done by using density measurements, and the Heckel and Kawakita equations, whereas the mechanical properties of the tablets were evaluated by using tensile strength (T--a measure of bond strength) and brittle fracture index (BFI--a measure of lamination tendency). The ranking for the mean yield pressure, P(y), for the formulations containing the different starches was generally corn < pigeon pea < plantain starch while the ranking for P(k), an inverse measure of the amount of plasticity, was pigeon pea < plantain < corn starch, which indicated that formulations containing corn starch generally exhibited the fastest onset of plastic deformation, whereas those formulations containing pigeon pea starch exhibited the highest amount of plastic deformation during tableting. The tensile strength of the tablets increased with increase in concentration of the starches while the Brittle Fracture Index decreased. The ranking for T was pigeon pea > plantain > corn starch while the ranking for BFI was corn > plantain > pigeon pea starch. The bonding capacity of the formulations was in general agreement with the tensile strength results. The disintegration time (DT) of the formulation increased with concentration of plantain and corn starches but decreased with concentration of pigeon pea starch. The general ranking of DT values was plantain < pigeon pea < corn starch. Notably, formulations containing pigeon pea starch exhibited the highest bond strength and lowest brittleness, suggesting the usefulness of pigeon pea starch in producing strong tablets with minimal lamination tendency. Plantain starch, on the other hand, would be more useful where faster disintegration of tablet is desired. The results show that the starches could be useful in various formulations depending on the intended use of the tablets with the implication that the experimental starches can be developed for commercial purposes.     

Compressional characteristics of native and pregelatinized forms of sorghum,plantain, and corn starches and the mechanical properties of their tablets

A study was made of the compressional characteristics of native and pregelatinized forms of sorghum, plantain, and corn starches and the mechanical properties of their tablets. Compressional characteristics were analyzed using density measurements and the Heckel and Kawakita plots. Pregelatinized starches exhibited more densification than native starches during die filling and at low pressures. The ranking for the mean yield pressure (Py) values for the starches was plantain < corn < sorghum, with the pregelatinized starches having lower values than the native starches. The ranking for the values of another pressure term, Pk--an inverse measure of plasticity, was corn < plantain < sorghum, but with the native starches having the lower values. For the tablets, the ranking for values of tensile strength (T) was corn > plantain > sorghum, while the ranking for the brittle fracture index (BFI) was plantain > corn > sorghum. Tablets made from pregelatinized starches had lower T and BFI values than those made from native starches. The results suggest that pregelatinization of the starches facilitated faster onset of plastic deformation but reduced the amount of plastic deformation which occurred during the compression process.     

Tabletability of Maltodextrins and Acetaminophen Mixtures

Abstract

Tabletability of five types of maltodextrin, a filler/binder excipient, was studied by testing their loading potentials with acetaminophen. The formulations consisted of excipient and acetaminophen at five different ratios and magnesium stearate at a 0.5% concentration. These mixtures were compacted employing an Integrated Compaction Research System at a constant punch velocity of 100 mm/sec. under varying applied pressures from 50 to 450 MPa. Compaction data were evaluated using the total work of compaction vs applied pressure plots whilst the post-compaction tests included the measurements of crushing force, disintegration time, and friability of the resulting tablets. Both the energy involved during the compaction of a formulation and the crushing force values of the resulting tablets decreased as the amount of the maltodextrin in a formulation was reduced. Maltodextrins exhibited adequate binding potential at acetaminophen drug loading levels of only up to twenty-five percent. The disintegration times of the tablets containing maltodextrins were generally prolonged and this was found to be due to the formation of a “gel” layer around the tablet which formed on immersion into water. The tabletability of maltodextrins were also compared to that of Fast-Flo lactose, and the compactability of these excipients were found to be similar.     

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.     

The effect of moisture on the physical characteristics of ranitidine hydrochloride tablets prepared by different binders and techniques

Abstract

The effect of moisture on the physical properties of ranitidine hydrochloride tablets prepared by direct-compression and by wet-granulation method using PVP or EC as binders was studied. Tablets adsorped moisture at 50 and 75 % RH (relative humidity) but lost moisture at 30% RH. Except storage at 75% RH, however, tablet volumes did not change significantly during the test period. Moisture sorption caused a decrease in strength of tablets except low humidity (30% RH). Also, the disintegration time of tablets showed a decrease at all conditions except 30% RH. Furthermore, generally dissolution profiles of tablets prepared by direct-compression and by ethyl cellulose remained unchanged. Changes in the binder type in the tablet formulations changed the water uptake properties and also the physical properties of tablets. Directly-compressed tablets were much susceptible to change caused by humidity than tablets prepared by wet-granulation.     

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.     

Preparation and characterization and release properties of Eudragit RS based ibuprofen pellets prepared by extrusion spheronization: effect of binder type and concentration

Objective: The effects of type and concentration of binding agent on properties of Eudragit RS based pellets were studied.

Materials and methods: Pellets containing ibuprofen (60%), Eudragit RS (30%), Avicel (10%) were prepared by extrusion spheronization. PVP K30, PVP K90, HPMC 6cp, HPMC K100LV or HPMC K4M were used as binders in concentrations of 2, 4 or 6% based on the total weight of formulation. The process efficiency, pellet shape, size distribution, crushing strength, elastic modulus and drug release were examined. The effect of curing on pellet properties was also investigated.

Results: The process of extrusion spheronization became difficult with increase in binder viscosity and/or concentration. An increase in binder viscosity and/or concentration resulted in reduction in the yield of pellets, wider particle size distribution and departure from spherical shape especially in the case of HPMC binder. The crushing strength and elastic modulus of pellets decreased with increase in PVPs concentration. However this was not the case for pellets containing HPMCs. Drug release rate increased as the concentration of binder increased. Pellets containing 2%w/w of PVP K30 showed the slowest release rate. For those pellets with brittle nature, curing changed the behavior of pellet under mechanical test to plastic deformation. Yield point and elastic modulus of all formulations decreased after curing. Curing decreased the drug release rate.

Conclusion: Binder type and concentration significantly affected the properties of pellets. For production of sustained release ibuprofen Eudragit RS based pellets lower viscosity binders (PVP K30) with concentrations less than 4%w/w was optimum.