Paracetamol Tablet Formulation Research Articles

The effect of some excipients on the physical properties of a paracetamol tablet formulation.

The effects of the addition of the excipients sorbitol, sodium lauryl sulphate and Aerosil on the physical properties of a paracetamol tablet formulation have been evaluated. Increase in the concentration of sorbitol and sodium lauryl sulphate caused a decrease in the hardness with a corresponding increase in the friability, disintegration and dissolution rates of the tablets. The mode of incorporation of the excipient, Aerosil, greatly influenced the physical properties of the paracetamol tablets. When added internally, the tablets' strength decreased while the friability, disintegration and dissolution rates increased. However, when Aerosil was added externally, the strength of the tablets increased while their friability, disintegration and dissolution rates decreased.

The effect of temperature on the plasto-elasticity of some pharmaceutical powders and on the tensile strengths of their tablets.

Measurements have been made of the stress relaxation (SR) during, and of the elastic recovery (ER) after, compression of four directly compressible excipients, and of chloroquine diphosphate and of a paracetamol tablet formulation at temperatures between -10 and +65 degrees C and of the tensile strengths of the tablets produced. It was found that at a fixed packing fraction, the stress relaxation and tensile strength of all the materials increased and the ratio ER/SR decreased as the compression temperature was raised. Tensile strength was inversely proportional to ER/SR at all the temperatures studied. Values for the activation energies (Eo) of bonding between particles for all the materials were derived from plots of the log of tensile strength and of log SR/ER versus the reciprocal of the absolute temperature. The values of Eo obtained from the latter plots tended to be higher than from the former by a factor of between 1.5 and 4.5.

Evaluation of Khaya Gum as a Binder in a Paracetamol Tablet Formulation

A study of the comparative effects of khaya gum and two standard binding agents, polyvinylpyrrolidone (PVP) and gelatin, on the compressional characteristics of a paracetamol tablet formulation and on the mechanical properties of the tablets was made. Compressional characteristics were analysed using density measurements and the Heckel and Kawakita plots. The loose initial relative density (D0) of the formulation increased with increased binder concentration while the packed initial relative density (Di) decreased. The degree of densification achieved for the formulation at low pressures (Db) and at both zero and low pressures (Da) decreased with increased binder concentration. The mean yield pressure (Py) for the formulation decreased with increase in binder concentration, with formulations containing khaya gum having the lowest Py values and those containing gelatin exhibiting the highest values. Another pressure term, Pk (an inverse measure of plasticity) decreased with increase in binder concentration, with formulations containing PVP having the lowest Pk values and those containing khaya gum and gelatin having similar Pk values. The tensile strength (T) of the paracetamol tablets increased with increase in binder concentration while the brittle fracture index (BFI) decreased. Tablets containing PVP exhibited the highest T values while those containing khaya gum exhibited the lowest values. The same trend was obtained for the BFI values with tablets containing khaya gum exhibiting the lowest values. The results suggest that khaya gum could be useful as a binding agent for particular tablet formulations.

Evaluation of Breadfruit and Cocoyam Starches as Exodisintegrants in a Paracetamol Tablet Formulation

Breadfruit and cocoyam starches have been evaluated as exodisintegrants in formulated paracetamol tablets and compared with corn starch. Tablet disintegration time and the hardness-friabrasion/disintegration time ratio were used to assess the disintegrant efficacy of the starches. Generally, it was found that the rank order of efficacy was corn starch > cocoyam starch > breadfruit starch. However, tablets containing the experimental starches had higher hardness values than those containing corn starch and may be useful in particular tablet formulations.

Effects of varying concentrations of <i>Dioscorea bulbifera</i> (Fam. Dioscoreaceae) startch on some physical properties of paracetamol tablet formation

Tablets of paracetamol BP prepared with purified starch obtained from the bulbs of locally cultivated Dioscorea bulbifera in comparison with corn starch BP, both at concentrations, 3-10 %w/w were evaluated for their disintegration time, mechanical properties and dissolution profiles. All the batches of tablets prepared with both starches disintegrated in less than 15 min. Although crushing strength above 60 N across the batches of tablets prepared with both starches were obtained but values of friability less than 1% were only obtained in batches of tablets containing 3 %w/w D. bulbifera and 7.5% w/w corn starches respectively. A plot of varying concentrations of the respective starches versus crushing strength-friability-ratio (CSFR) showed a continuous decrease in CSFR after the application of 3%w/w of D. bulbifera starch while it increased continuously at all the concentrations studied for corn starch. Dissolution profiles show that T-50 was attained in shorter times in the paracetamol tablets prepared with lower concentrations of D. bulbifera starch when compared with those of corn starch BP. Starch obtained from D. bulbifera may thus serve as alternative to corn starch as disintegrant if applied in concentration above 5 % w/w and as possible binder in concentrations less than 5 %w/w in paracetamol tablet formulation. Keywords: Dioscorea bulbifera starch, corn starch, tablet physical propertiesJournal of Pharmaceutical and Allied Sciences, Vol. 7 No. 5 (2010)

Evaluation of the Quantitative Effects of Variables on a Paracetamol Tablet formulation Prepared with Gum as Binding Agent

The individual and interaction effects of gum - binder type (B), binder concentration (C), as well as the relative density (D) of a paracetamol tablet prepared with Delonix regia seed gum (DRSG), acacia gum BP (ACG) and tragacanth gum BP (TRG) on the mechanical {tensile strength (TS) and brittle fracture index (BF} and disintegration {disintegration time (DT) and crushing strength-friability/disintegration time ratio (CSFR/DT)} properties of the tablets were studied using a 2 3 factorial experimental design. For the TRG/ACG and DRSG/ACG, the individual effects of the variables presented a rank order of D>C>B on the two mechanical properties studied, while a rank order of B>C>D was obtained for the studied disintegration properties. However, considering the TRG/DRSG combination, effect of C was more on the DT (C>D>B), whereas D had more effect on the CSFR/DT (D>C>B). Generally, the interaction between B and C was more on TS and DT than on BFI and CSFR/DT, while a similar result was observed for B and D on BFI and CSFR/DT than on TS and DT. This implies that the B is a very important variable to be considered when combining binders in a formulation.

Preliminary study of Anacardium occidentale gum as binder in formulation of paracetamol tablets

An attempt was made to investigate the binding efficacy of cashew nut tree gum in tablet formulation in comparison with standard binders such as acacia and polyvinyl pyrrolidone (PVP K-30). The paracetamol granules were prepared with different concentration of the gum as binder by wet granulation method. The granules were evaluated and found to be satisfactory for preparing compressed tablets. The tablets were prepared from the granules by hydraulic hand press and evaluated for volume of tablet, apparent density, porosity, relative density (or) packing fraction, percentage elastic recovery, tablet physical stability, content uniformity, weight variation, hardness, friability, disintegration time, in vitro dissolution studies and surface analysis by SEM. Formulations containing the minimum concentration of 2.5% cashew nut tree gum as binding agent show short disintegration and fast dissolution including good physico-mechanical properties. The result suggests that cashew nut tree gum can be used as an alternative binder with 2.5% concentration to produce a tablet of better mechanical strength and dissolution profile of particular drug substance.

Patient Preference for Sustained-Release versus Standard Paracetamol (Acetaminophen): A Multicentre, Randomized, Open-Label, Two-Way Crossover Study in Subjects with Knee Osteoarthritis

Guidelines for osteoarthritis (OA) management recommend paracetamol (acetaminophen) as the most appropriate first-line analgesic for mild to moderate pain. Standard paracetamol requires four times daily dosing. Drug compliance and convenience are inversely related to daily dose frequency. Compliance is a pivotal component of the successful management of OA pain and is influenced by patient preferences or beliefs. The added convenience of three times daily dosing may enhance compliance and, therefore, pain relief. This multicentre, randomized, open-label, two-way crossover, phase IV study is the first to evaluate patient preference with a sustained-release paracetamol tablet formulation designed for three times daily dosing. Compared with standard paracetamol tablets dosed four times daily, the sustained-release formulation was preferred in a 2:1 ratio, provided better overall joint pain relief, resulted in higher levels of satisfaction in subjects with OA of the knee and has the potential to improve patient compliance and, therefore, pain control.

Effect of Grewia gum on the mechanical properties of paracetamol tablet formulations

Grewia gum has been evaluated as a binder in paracetamol tablet formulations. Compressional properties of the formulations were analyzed using density measurements and the compression equations of Heckel and Kawakita as assessment parameters. Formulations containing Grewia gum as a binder show a slower onset and lower amount of plastic deformation than those containing PVP. The Db values for formulations containing Grewia gum, increased with increased concentration up to 4% w/w. Formulations containing Grewia gum were also found to exhibit higher degree of packing than those containing PVP. Yield values for formulations containing Grewia gum was found to be at variance with the binder concentration. The values increased between 1 and 2% w/w and decreased between 2 and 4% w/w. A linear relationship was found to exist between N/C and N for formulations containing Grewia gum at all concentrations. Grewia gum was found to improve the fluidity of paracetamol granulation better than PVP. This study suggests that Grewia gum compares favorably with the standard binder PVP used hence could be a useful substitute binder in paracetamol tablet formulations. Key words: Grewia gum, PVP, paracetamol, Heckel equation, Kawakita equation, compaction characteristics.

Comparative Evaluation of the Binding Properties of Two Species of Khaya Gum Polymer in a Paracetamol Tablet Formulation

A study was made of the comparative effects of polymers obtained from two species of khaya tree – Khaya senegalensis and Khaya grandifoliola – as binding agents in a paracetamol tablet formulation. The mechanical properties of the tablets were assessed using the tensile strength (T), brittle fracture index (BFI) and friability (F) of the tablets while the drug release properties of the tablets were assessed using disintegration and dissolution times. The tensile strength, disintegration and the dissolution times of tablets increased with the increase in binder concentration while F and BFI decreased. K. senegalensis gum produced tablets with stronger mechanical properties with less tendency to laminate, and longer disintegration and dissolution times than K. grandifoliola gum. The results suggest that the polymer gum from K. senegalensis will be more appropriate as a binding agent than the gum from K. grandifoliola when higher mechanical strength and slower release profiles of tablets are desired.

Evaluation and Optimization of Godare Starch as a Binder and Disintegrant in Tablet Formulations

The binding and disintegrating properties of Godare (Colcosia esculenta) starch in paracetamol tablet formulations were evaluated in comparison with potato starch. Tablet crushing strengths (Hs), friabilities Frs), disintegration times (DTs) and porosities were determined. The results showed that Godare starch has a better binding ability than potato starch giving tablets of higher H, lower Fr and porosity. Its disintegrating efficacy is comparable to that of potato starch. Optimum binder and disintegrant concentration of Godare starch was obtained by employing a 22 factorial design. Statistical analysis showed that as a binder, Godare starch provided paracetamol tablets with desired properties (88.1 N H, 2.69 min DT and 0.74% Fr) when used at 6.3% w/w concentration and compressed at 18.75 KN. As a disintegrant, Godare starch at 7% w/w concentration, provided tablets with a H of 109.1 N, DT of 3.22 min and 0.88% Fr, when the formulation contained povidone as a binder and AC-Di-Sol® as a disintegrant and compressed at 19 KN. Keywords: Godare starch, paracetamol, binders, disintegrants, experimental design Ethiopian Pharmaceutical Journal Vol. 24 (2) 2006: pp.98-105

Influence of process variables on release properties of paracetamol tablets

A 2(3) factorial experimental design has been used to quantitatively study individual and interaction effects of the nature of binder (N), binder concentration (c) and relative density of tablet (d) on the disintegration time (DT) and dissolution times, t1, t50 and t90, of paracetamol tablet formulations. The factorial design was also used to study the quantitative effects of pregelatinization of starch binders on these parameters, i.e., N, c and d. In general, the most common ranking of the individual effects on DT, t1, t50 and t90 for native/native, pregelatinized/pregelatinized and native/pregelatinized starch binder formulations was c > d > N. For interaction effects, the most common ranking was N-c > c-d > N-d for all formulations. The results generally showed that c can considerably affect DT, t1, t50 and t90 of the tablets.

Influence of Delonix regia seed gum on the compressional characteristics of paracetamol tablet formulations

Gum obtained from the seed of Delonix regia (Bojer ex Hook) Raf. Family Fabaceae was employed as a binder in a paracetamol tablet formulation with tragacanth and acacia BP as official standard gum binders. The effect of the Delonix regia seed gum (DRSG) in the formulation was evaluated using density measurements and the Heckel and Kawakita equations for the analysis of the results. The results suggest that the granules containing DRSG have comparable packing property with those of tragacanth gum (TRG) and acacia gum (ACG). The deformational indices i.e. P y and P k obtained from the granules containing the three gum binders reflect a comparable pattern among the formulations. Furthermore, the results showed that the P k an index of deformation occurring during compression does not necessarily depend on the P y an index of deformation at onset of compression of the granules. This work concludes that DRSG may be substituted for TRG and ACG.

Comparative disintegrant activities of breadfruit starch and official corn starch

A Comparative evaluation of starch powder extracted from breadfruit ( Artocarpus communis, Frost) as tablet disintegrant was made with corn starch BP using a 2 × 4 factorial experiment in a randomized complete block design. Two factors (type of starch: 2 i.e. breadfruit and corn) at four levels (concentrations of starch disintegrant: 4 i.e. 2.5%, 5%, 7.5% and 10%) were studied. One (1) kilogram batches of paracetamol granules containing various concentrations of endo-disintegrant or exo-disintegrant were prepared by the wet granulation method in a combined mixer–granulator, using polyvinyl pyrrolidone solution as binder. Tablets were tested for disintegration, dissolution and physical qualities following the British Pharmacopoeia (BP) compendial procedures. At the compression force of 1 tonne, corresponding to average packing fraction of 0.92, all formulations containing breadfruit and corn starch exo-disintegrants passed the official disintegration time limit of ≤ 15 min and quantity dissolved ( Q 30) of ≥ 80% in 30 min. As endo-disintegrant however, only corn starch at 5% and 10% w/w and breadfruit at 10% passed the BP limit test. Generally, the rank order of effectiveness of disintegrant was Corn exo ≈ Breadfruit exo > Corn endo > Breadfruit endo. The observed concentration-dependent difference in disintegrant effectiveness is ascribed to the differences in their hydration capacity and effective tablet porosity. Contrary to faster disintegration suggested by its higher hydration capacity, breadfruit starch formulations showed longer disintegration time than corn, attributable to the higher density of breadfruit formulations which appears to retard entry of disintegration fluid into the tablet. However, the dissolution profiles ( Q 30) were comparable ( p > 0.05). Breadfruit starch powder appears to be a suitable substitute for official corn starch only as exo-disintegrant in paracetamol tablet formulation. In that form, it not only produced rapid tablet break-up and drug dissolution, it also improved tablet crushing strength.

Effects of plantain and corn starches on the mechanical and disintegration properties of paracetamol tablets

The effects of plantain starch obtained from the unripe fruit of the plant Musa paradisiaca L. (Musaceae) on the mechanical and disintegration properties of paracetamol tablets have been investigated in comparison with the effects of corn starch BP using a 2(3) factorial experimental design. The individual and combined effects of nature of starch binder (N), concentration of starch binder (C), and the relative density of tablet (RD) on the tensile strength (TS), brittle fracture index (BFI), and disintegration time (DT) of the tablets were investigated. The ranking of the individual effects on TS was RD > C >> N, on BFI was C >> RD > N and on DT was N > C > RD. The ranking for the interaction effects on TS and DT was N-C >> N-RD > C-RD, while that on BFI was N-C >> C-RD > N-RD. Changing nature of starch from a "low" (plantain starch) to a "high" (corn starch) level, increasing the concentration of starch binding agent from 2.5% to 10.0% wt/wt, and increasing relative density of the tablet from 0.80 to 0.90, led to increase in the values of TS and DT, but a decrease in BFI. Thus, tablets containing plantain starch had lower tensile strength and disintegration time values than those containing corn starch, but showed better ability to reduce the lamination and capping tendency in paracetamol tablet formulation. The interaction between N and C was significantly (P < .001) higher than those between N and RD and between C and RD. There is therefore the need to carefully choose the nature (N) and concentration (C) of starch used as binding agent in tablet formulations to obtain tablets of desired bond strength and disintegration properties. Furthermore, plantain starch could be useful as an alternative binding agent to cornstarch, especially where faster disintegration is required and the problems of lamination and capping are of particular concern.

A sensitive and rapid assay for 4-aminophenol in paracetamol drug and tablet formulation, by flow injection analysis with spectrophotometric detection

4-Aminophenol (4AP) is the primary degradation product of paracetamol which is limited at a low level (50 ppm or 0.005% w/w) in the drug substance by the European, United States, British and German Pharmacopoeias, employing a manual colourimetric limit test. The 4AP limit is widened to 1000 ppm or 0.1% w/w for the tablet product monographs, which quote the use of a less sensitive automated HPLC method. The lower drug substance specification limit is applied to our products, (50 ppm, equivalent to 25 μg 4AP in a tablet containing 500-mg paracetamol) and the pharmacopoeial HPLC assay was not suitable at this low level due to matrix interference. For routine analysis a rapid, automated assay was required. This paper presents a highly sensitive, precise and automated method employing the technique of Flow Injection (FI) analysis to quantitatively assay low levels of this degradant. A solution of the drug substance, or an extract of the tablets, containing 4AP and paracetamol is injected into a solvent carrier stream and merged on-line with alkaline sodium nitroprusside reagent, to form a specific blue derivative which is detected spectrophotometrically at 710 nm. Standard HPLC equipment is used throughout. The procedure is fully quantitative and has been optimised for sensitivity and robustness using a multivariate experimental design (multi-level ‘Central Composite’ response surface) model. The method has been fully validated and is linear down to 0.01 μg ml −1. The approach should be applicable to a range of paracetamol products.

Characterization of Khaya Gum as a Binder in a Paracetamol Tablet Formulation

ABSTRACTThe influence of khaya gum, a binding agent obtained from Khaya grandifolia (Meliaceae family), on the bulk, compressional, and tabletting characteristics of a paracetamol tablet formulation was studied in comparison with the effects of two standard binders: polyvinylpyrrolidone (PVP; molecular weight 40,000) and gelatin. The relative ability of khaya gum to destroy any residual microbial contamination in the binder or in the formulation during tabletting was also studied using Bacillus subtilis spores as a model.Formulations containing khaya gum exhibited more densification than formulations containing PVP and gelatin during die filling, but less densification due to rearrangement at low pressures. The mean yield pressure of the formulation particles obtained from Heckel plots, and another pressure term, also inversely related to plasticity, obtained from Kawakita plots, showed dependence on the nature and concentration of the binder, with formulations containing khaya gum exhibiting the lowest and highest values respectively. The values of the pressure terms suggest that the yield pressure relates to the onset of plastic deformation during compression, while the Kawakita pressure relates to the total amount of plastic deformation occurring during the compression process.Tablets made from formulations containing khaya gum had the lowest tensile strength values but also the lowest tendency to laminate or cap, as indicated by their lowest brittleness. All the tablets had friability values <1% at higher concentrations of the three binders. In addition, khaya gum demonstrated a comparable ability to destroy microorganisms in the formulation during tabletting as the two binders.The characterization of the formulations suggests that khaya gum can be developed into a commercial binding agent for particular tablets.

A five way crossover human volunteer study to compare the pharmacokinetics of paracetamol following oral administration of two commercially available paracetamol tablets and three development tablets containing paracetamol in combination with sodium bicarbonate or calcium carbonate

This report concerns a single dose randomized five way crossover study to compare the pharmacokinetics of paracetamol from two commercially available paracetamol (500 mg) tablets and three different development paracetamol (500 mg) tablet formulations containing either sodium bicarbonate (400 mg), sodium bicarbonate (630 mg) or calcium carbonate (375 mg). The results demonstrated that addition of sodium bicarbonate (630 mg) to paracetamol tablets, increased the rate of absorption of paracetamol relative to conventional paracetamol tablets and soluble paracetamol tablets. Addition of sodium bicarbonate (400 mg) to paracetamol tablets increased the absorption rate of paracetamol relative to conventional paracetamol tablets, but there was no difference in the rate of absorption compared to soluble paracetamol tablets. Inclusion of calcium carbonate (375 mg) to paracetamol tablets had no effect on absorption kinetics compared to the conventional paracetamol tablet. The faster absorption observed for the sodium bicarbonate formulations may be as a result of an increase in gastric emptying rate leading to faster transport of paracetamol to the small intestine where absorption takes place.

Formulation and evaluation of sustained release paracetamol tablets.

Slow-releasing paracetamol tablet formulations were produced and their in vitro dissolution profiles and in vivo absorption characteristics were determined and compared with a conventional rapidly-disintegrating commercial formulation. A correlation between saliva and plasma levels of the drug was confirmed and this allowed estimation of some simple pharmacokinetic parameters from the saliva paracetamol data. The in vitro data correlated with the in vivo parameters and this enabled the dissolution test results to be used in predictive manner in the development of a compression-coated slow release formulation which produced therapeutic levels of the drug for up to 5 h.

Evaluation of Cassia roxburghii Seed Gum as Binder in Tablet Formulations of Selected Drugs

The purpose of the study was to evaluate cassia roxburghii seed gum powder as binder for paracetamol and diclofenac sodium. Granules of both drugs were prepared by wet granulation method. Two different laboratory developed methods were tried for the isolation of seed mucilage from seed powder. The phytochemical, physico-chemical and microbiological properties were performed on the seed gum and the pre-compression parameters like bulk density, tapped density, angle of repose, carr’s index and hausner’s ratio have shown that paracetamol and diclofenac granules prepared using Cassia roxburghii gum were well within the limits and comparable to those prepared using standard starch paste as binder. The in vitro dissolution study was performed for paracetamol formulations with sodium starch glycolate and the dissolution profile shows all the three formulations met with official specifications. The in vitro dissolution profile shows that drug release decreased in the order, tablets prepared by starch&gt;c.roxburghii defatted&gt;c.roxburghii filtered in both paracetamol and diclofenac formulations. The drug release from tablets prepared by C.roxburghii seed gum was more than 85% in 2 hours and filtered C.roxburghii gum has excellent mechanical, binding and release properties in paracetamol tablet formulations with the addition of sodium starch glycolate as an external disintegrant