Pharmaceutical Development and Technology, 13:197204, 2008 Copyright Informa Healthcare USA, Inc.

. ISSN: 1083-7450 print / 1097-9867 online DOI: 10.1080/10837450801949400

LPDT

Evaluation of Cocoa Butter as Potential Lubricant for Coprocessing in Pharmaceutical Tablets

Adebolu Adewole Adeagbo and Gbenga Alebiowu
Cocoa Butter as Lubricant for Coprocessing Tablets

Department of Pharmaceutics, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria

INTRODUCTION
The lubricant activity of cocoa butter coprocessed with magnesium stearate plus talc (CMT) was compared with magnesium stearate plus talc (MT) using flow and compressional characteristics of paracetamol granules and mechanical properties of their tablets as assessment parameters. The flow of the granules quantified as Hausners ratio, Carrs index, and angle of repose showed that CMT has a higher ability than MT to reduce densification of granules due to vibration. Compressional characteristics analyzed using density measurements and the Heckel and Kawakita plots revealed that CMT did not facilitate the increase in the densification of the granules during the filling and at low pressures, Db. Also, CMT reduced the plastic deformation of the granules measured by the Py-yield pressure at onset of plastic deformation and Pk-yield pressure of deformation under compression. The mechanical properties determined by the tensile strength, T, and brittle fracture index, BFI, of the tablets produced were affected by CMT. The T and BFI of tablets with CMT were lower than those of MT. The results suggest that though CMT lowered the plasticity of the granules, it improved their flow rate and assisted in producing tablets with fewer tendencies to cap or laminate. This work concluded that cocoa butter, an inexpensive and easily available lipid, is an effective and viable lubricant that can be co-processed with magnesium stearate/talc mixture for an efficient lubrication of granules and may be useful in reducing lamination and capping in formulations that are susceptible to these 2 defects of tablets. Keywords cocoa butter, magnesium stearate, Heckel plot, Kawakita plot, tensile strength, brittle fracture index

Received 31 July 2007; Accepted 24 October 2007. Address correspondence to Gbenga Alebiowu, Department of Pharmaceutics, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria; E-mail: galebiowu@yahoo.co.uk; galebiowu@oauife.edu.ng

Over the years, significant advances in the manufacturing processes of oral solid dosage forms have occurred, including the transition from tablet preparation by wet granulations to direct compression. Tablets produced by wet granulation are highly influenced by granule characteristics such as flowability, compressibility, and compactability.[1] The development of various added functionality excipients (AFE), which are used to achieve formulations with desired end effects, equally influence the quality of granules and the resulting tablets produced. AFE may be achieved by co-processing excipients with a view to providing a synergy of functional improvements as well as masking the undesirable properties of individual excipients.[2] Lipidsoily and fatty substancesby their nature exert some lubricity between surfaces that are in relative motion. It is therefore understandable that when applied in carefully regulated amounts, they could improve the lubricating efficiency of lubricants in general use. They have been studied for their effect on the characteristics of granules and tablets, ie, moisture content, tablet hardness, disintegration and dissolution, and the stability of active ingredients. NDiaye et al[3] and Aoshima et al[4] in their studies showed that lipids have no negative effect on tablet hardness. Aoshima et al[4] further showed that unlike magnesium stearate, which delays disintegration and dissolution of the active ingredient,[57] the fatty acid esters promotes a reduction in disintegration time. They concluded that the fatty acid esters are superior to magnesium stearate because the tablets containing them have better stability and are free of biological problems such as viral contamination, which may be due to the very low moisture content of the granules containing the fatty acid esters compared with those of other lubricants. In this work, cocoa butter, a cheap and easily available semisolid fatty substance, is co-processed with a

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50:50 mixture of magnesium stearate and talc. Presently, cocoa butter is not being used as a lubricant in the making of tablets, but is used in the pharmaceutical industry for manufacturing suppositories. The use of cocoa butter in suppositories is desirable because it is safe. It is not being used as a lubricant in tablets because it is a semisolid at room temperature. The aims of this study were thus to incorporate cocoa butter into a binary mixture of magnesium stearate/talc and to investigate the influence that cocoa butter would have on the lubricant activity of magnesium stearatetalc mixture using the flow, compressional, and mechanical properties of a paracetamol tablet formulation as assessment parameters. Hausner's ratio, Carrs index, and angle of repose were used to analyze the flow properties of the granules. In analyzing the compression data and the evaluation of tablet mechanical properties, the compression equations of Heckel[8] and Kawakita and Ludde,[9] and 2 measures of mechanical properties of tablets, ie, tensile strength and brittle fracture index, were used respectively. The Heckel equation is widely used for relating the relative density, D, of a powder bed during compression to the applied pressure, P. It is written as

granular materials and Vp is the bulk volume after compression. The constant a is equal to the minimum porosity of the material before compression while the constant b is related to the plasticity of the material. The reciprocal of b gives apressure term, Pk, which is the pressure required to reduce the powder bed by 50%.[11,12] Both the Heckel and Kawakita plots have their limitations and are believed to generally exhibit linearity at high and low pressures, respectively.[13] Therefore both were used in this study in the hope of obtaining more accurate information on the compressional characteristics of the paracetamol formulation. Bond strength and lamination tendency are 2 important mechanical properties of tablets, which are measurable by tensile strength and brittle fracture index values, respectively.[14] The brittle fracture index (BFI) was devised by Hiestand et al.[15] It is obtained by comparing the tensile strengths of tablets with a hole at their center, which acts as a built-in stress concentration defect, with the tensile strength of tablets without a hole. The BFI is defined as

BFI = 0.5 (T / To ) 1

(5)

In (1/1 D) KP + A

(1) where T is the tensile strength of the tablet without a hole and To is the apparent tensile strength of the tablet when a hole is presentboth at the same relative density. The BFI is a measure of localized stress relief within the tablet (at the edge of the hole) by plastic deformation. A low value of the BFI indicates the ability of the material to relieve localized stresses while a value approaching unity indicates a tendency of the material to laminate or cap.

The slope of the straight-line portion, K, is the reciprocal of the mean yield pressure, P, of the material. From the value of A the intercept, the relative density, Da, can be calculated using the following equation.[10]

Da = I e A

(2)

The relative density of the powder at the point when the applied pressure equals zero, Do, is used to describe the initial rearrangement phase of densification as a result of die filling. The relative density, Db, describes the phase of rearrangement at low pressures and is the difference between Da and Db.

MATERIALS AND METHODS The materials used were paracetamol BP, corn starch BP, and benzene (BDH Chemicals Ltd, Poole, UK); lactose BP (AB Knight and Co, London, UK); cocoa butter, magnesium stearate, and talc (Merck KGaA, Darmstadt, Germany); and ethanol (Sigma-Aldrich Laborchemikalien GMBH, Seelze, Germany).

D b = Da D o

(3)

The Kawakita equation is used to study powder compression and the degree of volume reduction, C. It is written as:

Preparation of Magnesium StearateTalc Lubricant Mixture Equal amounts of magnesium stearate and talc powders were triturated together using a porcelain mortar and pestle for a period of 5 min to ensure a uniform mixing of the 2 powders. The binary mixture (MT) was

C = Vo Vp/ Vo = abp/1 + bp

(4)

The equation in practice can be rearranged to give P/C = P/a + 1/ab, where Vo is the initial bulk volume for

Cocoa Butter as Lubricant for Coprocessing Tablets

199

sieved with a 120 mesh sieve (125 m) and then stored in a screw-capped bottle until needed.

Addition of Lubricants to the Granules Bottle number 1, ie, batch 1 with no lubricant, served as the control while granules in bottles numbered 2 through 7 were each mixed with 0.5% w/w, 1.0% w/w, 1.5% w/w, 2.0% w/w, 2.5% w/w, and 3.0% w/w, respectively of magnesium stearate talc (MT) lubricant mixture to produce batches 2 through 7. The bottles were then gently shaken with a flask shaker for 10 min each. The granules in bottle numbers 8 through 13 each received 0.5% w/w, 1.0% w/w, 1.5% w/w, 2.0% w/w, 2.5% w/w, and 3.0% w/w of coprocessed lubricant mix, ie, CMT, respectively, to produce batches 8 through 13.

Coprocessing of Magnesium StearateTalc Mixture with Cocoa Butter Cocoa butter weighing 1.20 g was placed inside a beaker containing 250 mL of 95% ethanol. This was then placed in a water bath set at 60C to allow for the melting and dissolving of cocoa butter in the ethanol. Magnesium stearatetalc mixture (MT) weighing 38.8 g was added and mixed with the ethanolic solution of cocoa butter in the beaker. The ethanol was allowed to evaporate from the mixture, and the remaining total mixture contained 3.0% w/w cocoa butter (this percent w/w is the optimum concentration obtainable from preliminary studies). The mixture (CMT) was placed in the dessicator for 72 h to allow for the ethanol to evaporate. The processed tertiary mixture (MT) was sieved with a 120-mesh sieve (125 m) and then stored in a screw-capped bottle until needed.

Determination of Physical Properties of Granules The moisture content of the batches was determined with an Ohaus moisture balance (Ohaus Scale Corp, Pine Brook, New Jersey). Particle densities were determined by the pycnometer method with benzene as the displacement fluid. The bulk density of each batch at zero pressure (loose density) was determined by pouring the granules at an angle of 45C through a funnel into a glass measuring cylinder with an internal diameter of 22 mm and a volume of 50 mL. The relative density (Do) of each batch was obtained from the ratio of its loose density to its particle density. The Hausner's ratio (HR), determined as the ratio of the initial bulk volume to the tapped volume, was obtained by applying 100 taps to 30 g of each batch in a graduated cylinder at a standardized rate of 38 taps per minute.[16] The Carr's index was obtained from the relationship ([tapped density bulk density/tapped density] 100). Statistical analysis (standard deviation at 0.95 confidence limit) was used to analyze the results, which are the means of 3 determinations.

Preparation of Binder Mucilage Starch mucilage was prepared by suspending 75 g of corn starch in 150 mL of distilled water. This was heated on a Bunsen flame with continuous stirring until mucilage was formed. The mucilage was used while still hot for more effective binding.

Preparation of Granules The wet granulation method of massing and screening was used. A 1500-g batch of a basic formulation of paracetamol (85% w/w), lactose (10% w/w), and cornstarch (5% w/w) was dry mixed for 5 min in a Hobart planetary mixer (Hobart Canada Inc, Don Mills, Ontario, Canada). The mixture was moistened with the starch mucilage. Massing was continued for 5 min and the wet mass was granulated by passing it through a number 12 mesh sieve (1400 m) using an Erweka (Model AR 400) granular (Erweka Apparatebau GmBH, Heusenstamn kr, Offenbach am Main, Germany). The resultant granulation was then dried in a hot air oven (Gallenhamp model OV335, Vindon Scientific Ltd, Oldham, UK) at 60C for 24 h. The dried granulation was screened through a number 16 mesh (1000 m) to produce the required grade of granulation, ie, fraction 355 710 m. This fraction obtained from the granules was then divided into 13 equal portions and stored in different screw-capped bottles (ie, numbers 113) until needed.

Preparation of Tablets From each batch, 550-mg quantities, giving a tablet thickness of 4.22 0.02 mm at zero porosity as calculated from particle density values, were compressed for 1 min with predetermined loads using a Carver hydraulic hand press (model C, Carver Inc, Menomonee Falls, Wisconsin). After ejection, the tablets were stored over silica gel for 24 h to allow for elastic recovery and hardening, and to prevent falsely low yield values. Their weights (w) and dimensions were then determined to within 1 mg and 0.01, respectively, and their relative densities (D) were calculated using the equation:

D = w/Vt rs

(6)

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in which Vt is the volume (cm3) of tablet and s is the particle density (gcm3) of the solid material. Heckel plots of In (1 / 1 D) vs applied pressure (P) and Kawakita plots P/C vs P were constructed for all batches.

Determination of Mechanical Properties The tensile strength of the normal tablets (T) and of apparent tensile strength (To) of those containing a hole, were determined at room temperature by diametral compression[17] using a Monsanto hardness tester (Monsanto Chemical Corp) and by applying the equation:

T = 2 F / dt

(7)

where T (or To) is the tensile strength of the tablet (MNm2), F is the load (MN) needed to cause fracture, d is the tablet diameter (m), and t is tablet thickness (m). Results were taken from tablets, which split cleanly into 2 halves without any sign of lamination. All measurements were made in triplicate or more and the results given are the means of several determinations. The BFI of the tablets were calculated using equation 6.

RESULTS AND DISCUSSION Table 1 presents the physical properties of the granules. Values of granular and bulk densities obtained for granulations containing cocoa buttertreated magnesium

stearate (CMT) are higher than for granulations containing magnesium streate plus talc (MT) alone and those with no lubricant. This implies that granules with CMT have more regular shapes, which may form fewer arches and bridges than granules with MT, hence, an increase in the packing per unit space. There was a general decrease in porosity as the lubricant concentration increased. It is possible that increasing lubricant concentration yielded granules with more regular shapes. These regular shapes may be caused by coating of the granule surfaces by the lubricants. It had been observed that because of granule geometry, mechanical forces may exist in granulation, which tends to influence the packing.[18,19] The values of porosity for granules containing CMT are lower than those of granules treated with MT. This suggests that cocoa butter would assist in reducing pockets of unwanted air vacuoles in the tablet. These air vacuoles may cause capping and lamination in tablets.[20] HR[21] provides an indication of the degree of densification that could result from vibration of the feed hopper, eg, during tableting, with values above 1.2 predicting significant densification of powders. The values obtained (Table 1) generally show that it decreases with increase in lubricant concentration. Although values obtained for the granulations in all cases fall within the predicted standard value of less than 1.2, lower values predicting better flowing granules were obtained for granules treated with CMT. The Carr's compressibility index[22] is a direct measure of the potential powder arch or bridge strength and stability; a less than 20% standard value suggests free-flowing granules. The values presented in Table 1 suggest that the granules on

Table 1 Physical properties of the granules Lubricant Magnesium stearate + talc % w/w 0.0 0.5 1.0 1.5 2.0 2.5 3.0 0.5 1.0 1.5 2.0 2.5 3.0 Granular density 1.329 1.332 1.349 1.362 1.378 1.418 1.454 1.372 1.410 1.434 1.454 1.467 1.517 Loose bulk density 0.442 0.448 0.459 0.466 0.473 0.488 0.509 0.536 0.554 0.564 0.565 0.567 0.572 Hausners ratio ( SD)* 1.178 (0.016) 1.176 (0.020) 1.156 (0.018) 1.146 (0.015) 1.169 (0.020) 1.151 (0.022) 1.153 (0.020) 1.162 (0.015) 1.093 (0.021) 1.086 (0.019) 1.090 (0.016) 1.093 (0.021) 1.092 (0.021) Carrs index (%) ( SD)* 15.10 (0.01) 14.90 (0.01) 13.50 (0.02) 12.70 (0.01) 14.40 (0.03) 13.10 (0.01) 13.20 (0.01) 13.90 (0.01) 8.50 (0.03) 7.90 (0.01) 8.20 (0.01) 8.50 (0.02) 8.40 (0.02) Angle of repose ( SD)* 41.36 (0.08) 27.68 (0.06) 28.15 (0.05) 28.87 (0.05) 29.08 (0.07) 29.29 (0.05) 29.85 (0.06) 23.85 (0.04) 24.25 (0.05) 26.57 (0.06) 26.82 (0.04) 27.57 (0.03) 27.60 (0.03) Moisture content 1.10 1.40 1.40 1.38 1.36 1.35 1.35 1.54 1.53 1.54 1.57 1.58 1.57 % porosity 66.84 66.40 66.00 65.80 65.70 65.60 65.00 61.20 60.80 60.70 60.60 59.95 59.80

Cocoa butter + magnesium stearate + talc

*n = 3.

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201

treatment with the lubricants are free flowing. The lower values obtained for the CMT-lubricated granules also suggest that the cocoa butter would facilitate reduction in arching or bridging of the granules and, hence, assist the free flow of the granules. The values for the angle of repose, a characteristic of the internal friction or cohesion of granules (shown in Table 1), further suggest that the CMT assisted the flow properties of the paracetamol granules. The values generally are below the 30C range considered appropriate for solid dosage form technology. The percent moisture content for granules with CMT is higher than that for the granules with MT. This could be due to the hygroscopic nature of cocoa butter. Figure 1 shows representative Heckel plots for paracetamol granules containing 0% w/w and 2% w/w of each of the lubricants. Two phases of compression are discernible in the plots with the second phase commencing approximately at 143.91 MNm2. Values of mean yield pressure, Py, were calculated from the region of the plots showing the highest correlation coefficient for linearity of > 0.994 for all the batches (generally between 63.96 and 143.91 MNm2). The intercept, A, was determined from the extrapolation of the region for the calculation of Py; the values of Da and Db were calculated from equations 2 and 3, respectively. The values of Py, Do, Da, and Db for all the starches are presented in Table 2. The values of Do for the various batches increased with the increase in lubricant concentration, implying that the initial packing of the granules in the die as a result of die filling increased with increase in lubricant concentration, which would facilitate more packing due to reduction in intragranular friction. It can be observed that the Do values for the granules containing CMT were higher than

3.5 3 2.5 2 1.5 1 0 50 100 150 200 250 Applied pressure (MNm2)

Figure 1. Heckel plots for granulation containing 0.0% w/w () and 2.0 w/w MT (), CMT ().

those for the granules with MT, showing that the CMT facilitated a higher initial packing of the granules in the die due to the presence of cocoa butter. Db represents the phase of rearrangement of particles at low pressure. It can be observed that the Db values for the granules with CMT were lower than those for the granules with MT. This suggests more fragmentation of granules with MT at low pressures than for granules with CMT and subsequent filling of void spaces between the particles.[23,24] These values are also found to be increasing with increase in lubricant for the granules. This implies that with increase in concentration, the lubricants would facilitate more packing of granules in the die and increase intergranular contact at low pressures. The values of Da represent the total degree of packing achieved at zero pressure. The values at low pressures are higher for granules with MT than those with CMT. These values are seen to increase with increase in lubricant concentration. The mean yield pressure, Py, is inversely related to the ability of a material to deform plastically under pressure. The values of Py for the batches with CMT were higher than for those with MT. This implies that the onset of plastic deformation in the granules with CMT occurred at higher pressures. The values of Py for granules treated with MT generally increased with increase in lubricant concentration, while for granules with CMT, a decrease was initially observed up to 2.0% w/w lubricant concentration before an increase was observed. This observation for CMT-treated granules could be due to the fact that cocoa butter, a semisolid fat, will enhance the chances of the granules to undergo the mechanism of powder consolidation relating to asperitic melting of the local surfaces of particles, particularly at higher compressional loads. This consolidation could be responsible for the increase in Py at higher lubricant concentration for CMT-treated granules. However, the Py value of the base granulation is comparable to what would be expected from an 85% w/w formulation of paracetamol. The Py of pure paracetamol was reported by others[25,26] to be 96.9 and 110 MNm2. Figure 2 shows representative Kawakita plots for paracetamol granules containing 0% w/w and 2% w/w of each of the lubricants. A linear relationship was obtained at all compression pressures used with a correlation coefficient of 0.999 for all the batches, thus, the Kawakita equation was used to predict the densification mechanism of the paracetamol granules. Values of a and ab were obtained from the slope and intercept of the plots, respectively. Values of 1-a give the initial relative density of the batches, Di, while Pk values were obtained from the reciprocal of values of b. The values of Di and Pk are included in Table 2. The Di values increased with increase in lubricant concentration,

ln 1/1-D

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A.A. Adeagbo and G. Alebiowu Table 2 Parameters obtained from density measurements and from Heckel and Kawakita plots for the paracetamol tablets formulation

Lubricant None Magnesium stearate + talc

Concentration (% w/w) 0.0 0.5 1.0 1.5 2.0 2.5 3.0 0.5 1.0 1.5 2.0 2.5 3.0

Do 0.332 0.336 0.341 0.342 0.343 0.344 0.350 0.388 0.392 0.393 0.394 0.401 0.402

Py MNm2 110.580 88.890 110.951 121.684 134.803 147.759 391.911 299.718 181.429 178.759 171.781 264.370 410.350

Da 0.726 0.710 0.715 0.723 0.745 0.763 0.804 0.708 0.715 0.720 0.725 0.768 0.775

Db 0.394 0.378 0.375 0.381 0.402 0.419 0.454 0.320 0.323 0.327 0.331 0.379 0.383

Di 0.535 0.453 0.528 0.564 0.569 0.572 0.577 0.570 0.569 0.574 0.588 0.586 0.584

Pk MNm2 0.035 0.068 0.059 0.053 0.055 0.058 0.065 0.067 0.065 0.060 0.063 0.065 0.068

Cocoa butter + magnesium stearate + talc

600

500

400

P/C

300

200

100

0 0 50 100 150 200 250 Applied Pressure (MNm2)

Figure 2. Kawakita plots for granulations containing 0.0% w/w () and 2.0% w/w lubricant MT (), CMT ().

with Di values for the batches treated with CMT being higher than those for the batches with MT. The Di values are also seen to be higher than the values of Do. Bearing in mind that the methods of determination of Do and Di have their limitations,[13,23] the differences in the values of Do and Di are probably due to the fact that while Do describes the loose initial relative density of the batches due to die filling, Di provides a measure of the packed initial relative density of the batches with the application of small pressure or what may be referred to as tapping of the granules.[27] Low values of Pk indicate materials that are soft and that readily deform under pressure. Table 2 shows that the

values of Pk for the batches initially decreased with increase in lubricant concentration up to 1.5% w/w, but increased from 2.0% w/w lubricant concentration. This suggests that there is a limit to which inclusion of lubricant in the granules could assist in increasing deformation under load. The values of Pk for the batches treated with CMT are higher than those treated with MT. This indicates that the inclusion of cocoa butter in the lubricant mix did not necessarily increase the softness of the granulation and its ability to deform plastically under pressure more than those containing MT. The influence of the type and concentration of lubricant does not appear to be clear-cut. Alebiowu and Itiola[23] have shown that Py is different from Pk in that while the Py value relates essentially to the onset of plastic deformation during compression, the Pk value appears to relate to the total amount of plastic deformation occurring during the compression process. Thus, the present results suggest that the use of CMT would not necessarily facilitate the onset of plastic flow and improve the total amount of plastic flow in the paracetamol granules when compared with the use of MT. The results of the tensile strength tests on the paracetamol tablets were found to fit the general equation:

Log T (or To ) = AD + B

(8)

with a correlation coefficient of > 0.963. A and B were constants, which depended on the nature and concentration of binder present in the formulation and on whether the tablet had a hole in it or not. Representative plots for tablets made from batches containing 0.0% w/w and 2.0% w/w of lubricants are presented in Figure 3. It can be seen that at all relative

Cocoa Butter as Lubricant for Coprocessing Tablets

0.2
Log tensile strength (MNm2)

203

0.1

0.4

0.7 0.82

0.85

0.88 0.91 Relative density

0.94

0.97

Figure 3. Log tensile strength versus relative density for paracetamol tablets containing 0.0% w/w () and 2.0% w/w lubricant MT (), CMT (); with () and without a hole () at the center.

would assist in melting of the asperities due to the heat produced during compression. On cooling, these asperities would solidify to form solid bonds between the particles.[29] With increase in lubricant concentration, these facilitated solid bonds would assist in increasing reduction in the lamination and capping tendency of the CMT tablets on ejection from the die. It can also be observed that at all lubricant concentrations, tablets containing CMT generally have lower T values than tablets with MT. This could be due to the higher amount of plastic deformation occurring at both the onset of compression, Py, and during the compression process, Pk, for MT-treated granules. The tensile strength and BFI results suggest that paracetamol tablets containing CMT had the lowest bond strength and brittleness. Thus, CMT could be a more useful lubricant than MT when problems of lamination and capping are of more importance than bond strength, especially on high-speed tableting machines with short dwell time for the plastic deformation of materials.

densities the tensile strength of a tablet with a hole was less than that of the same without a hole, the hole acting as a stress concentrator.[15,28] Values of T and BFI for all batches at D = 0.90, which is representative of commercial paracetamol tablets, are presented in Table 3. It can be seen that the values of T generally increased with increase in lubricant concentration for tablets containing MT, while tablets with CMT generally decreased in T. This same trend was obtained for BFI values, with tablets containing CMT having the lowest BFI value. It could be due to the presence of cocoa butter, which, being a semisolid fat,
Table 3 Tensile strength and brittle fracture index values for paracetamol tablets at a relative density of 0.90 Concentration (% w/w) 0.00 0.50 1.00 1.50 2.00 2.50 3.00 0.50 1.00 1.50 2.00 2.50 3.00 Tensile strength (MNm2) 0.448 0.452 0.570 1.016 1.007 0.951 0.995 0.423 0.902 0.863 0.830 0.752 0.731 Brittle fracture index 0.084 0.561 0.583 0.609 0.687 0.692 0.701 0.668 0.422 0.319 0.112 0.038 0.014

CONCLUSIONS The results of the present work conclude that cocoa butter coprocessed with MT would:
Enhance the packing and flow properties of the parace-

tamol granules
Increase both the loose relative density (ie, Do) and Not necessarily increase the plasticity of the granulation

packed relative density (ie, Di) of the granules in the die

Lubricant None Magnesium stearate + talc

as shown in the values of Py, onset of plastic deformation during compression, and Pk, total amount of plastic deformation occurring during compression, which were higher for the granules containing CMT than for those containing MT Not assist in increasing the bonding strength of the paracetamol tablets, but facilitate the reduction in the capping and lamination tendency of the tablets Cocoa butter, an inexpensive and easily available lipid, is an effective and viable lubricant which can be coprocessed with MT for an efficient lubrication of granules and be useful in reducing lamination and capping in formulations that are susceptible to these 2 defects of tablets

Cocoa butter + magnesium stearate + talc

REFERENCES
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