Effect of Compaction Forces on Powder Bed Permeability of Magnesium Silicate "Common Excipient Mixture"

Effect of Compaction Forces on Powder Bed Permeability of Magnesium Silicate "Common Excipient Mixture" SAMEER AL-ASHEH a, FAWZI BANAT a, ALA A SALEM a, IAD RASHID b, ADNAN BADWAN b a Department of Chemical Engineering, Jordan University of Science and Technology, P.O.Box 3030 Irbid 22110, JORDAN, alasheh@just.edu.jo http://www.just.edu.jo/eportfolio/pages/default.aspx?email=alasheh b The Jordanian Pharmaceutical Manufacturing Co PLC, P.O. Box 94, Naour 11710 Jordan, dr_iyad_rashid@hotmail.com Abstract: - This work involves development of new alternative excipient of starch-mgsio 3 mixture using dry-granulation techniques and influent of different parameter on the granulation process. Permeability using Darcy's law and swell capacity of excipients at different MgSiO 3 levels (from zero% to 90% w/w MgSiO 3 ) was investigated at different dry granulation roll compaction pressure. Different parameters were measured for compaction of MgSiO 3 at a given concentration; these include weight variation, hardness, disintegration time, particle size distribution and BET surface area. Starch-MgSiO 3 mixtures at different MgSiO 3 concentrations were evaluated for their permeability, swelling capacity, disintegration time and BET surface area. A system of starch-mgsio 3 mixture with 30% MgSiO 3 at third dry granulation roll compaction level was the most applicable one. The highest hardness value of 318.2 kg was achieved with low disintegration time of 8 sec and 5.65 m 2 /g specific surface area. This study demonstrates that starch-mgsio 3 mixture can serve as superdisintegrant excipients in wide applications of pharmaceutical manufactory. Key-Words: - Excipients, compaction, granulation, starch, MgSiO 3 1 Introduction Scalable processes in the field of pharmaceutical industry necessitate a full investigation of process parameters and variables at the small scale level for the purpose of attaining optimized operating conditions. One of the newly operation unit that has an added value and/or short cut pharmaceutical significance is what is known as the compactor. The added value is due to the fact that pharmaceutical powder blends produced by compaction results in an improvement in the powder physical properties towards highly flowable with high compaction features [1]. From economical point of view, it is reported that the presence of compactors eliminates the need of other processes that may require more labors, time, and cost burden mainly the granulation step in the field of pharmaceutical industry [2]. As powder physical requirements, ideal pharmaceutical blends should be characterized by good compaction and flow. As powder functional requirements, excipients composing the pharmaceutical powder blends serve as either binders or fillers or disintegrants or lubricants. Hence, the combination of different excipients in solid dosage form preparation creates solid, intact, disintegrable tablets. In this respect, the challenging opportunity is to achieve an excipient with multi-functioning purposes serving as a binder, filler and a disintegrant. Recently, the combination of magnesium silicate and starch particles was found to offer industrial potential for use as single filler. Such combination serves as binding as well as superdisintegration properties ISBN: 978-1-61804-137-1 58

and can be used directly in compressed tablets or in wet granulation methodologies [3]. The physical combination between starch and magnesium silicate is normally performed through co-precipitation of magnesium silicate onto starch or by compaction of starch with magnesium silicate [4]. The former technique was comprehensively investigated and was adopted in solid dosage form preparations [5]. However, scalability becomes a constraint as co-precipitation of magnesium silicate onto starch dictates the use of large volumes of operation units to fully contain a batch or fed batch process [4, 5]. The later technique, i.e. compaction of starch with magnesium silicate at different compaction pressure/ roller compactor, has not yet been investigated, and may provide a good alternative to the co-precipitation technique. This work aims to develop alternative excipients using dry granulation roller compactor as compared to co-precipitation technique. It is also intended to study the effect of compaction forces on the powder permeability. In this regard, Darcy lawpermeability will be used to study the powder's behavior. In contrast to the wet granulation process (e.g. fluid bed process and high shear mixing), the dry granulation roll compactor is the most useful granulation technology as it is simple, does not require liquid binder, ideal for materials that are sensitive to heat and/or moisture, micro problem does not exist, and economically feasible. 2 Materials and Methods 2.1 Equipment The following equipment were used during the course of experimental work: 1. Bench top compaction system (TFC-LAB Micro, USA), with capacity of 5 g to 1 kg/hr, roll speed of 0.1-4.0 rpm and roll force of 0.0 1.4 tons. 2. Single punch tablet compression (Manesty, Merseyside, UK), which is used for compression test. 3. Malvern Mastersizer 2000 laser Diffraction (Scirocco 200, UK). This is for particle size analysis; it measures particle size in the range 0.02-2000 µm. The system is controlled by mastersizer computer's software, with vibration feed rate from 0-100% and dispersive air pressure from 0 to 4 bar (± 0.02 bar). 4. Hardness tester device (Vector schleuniger, model 6D, 110 volts, Switzerland). 5. Disintegration tester (BJ series model). This is used for determination of disintegration time of tablet under certain condition at 37 C. 6. Bio-rad Tube (Econo-Column, Hercules, USA). These are tubes of 70 cm height; consist of porous polymer bed at the bottom of the biorad column to keep fine particles with internal diameter of 2.4 cm. Also it is equipped at the bottom of the column with an end cap to prevent or water leakage. The tube is used for powder samples in permeability test. 2.2 Materials Commercial maize starch, corn starch (Beijing Quanfeng Starch Company, China) was used. It was dried at 120 C until its water content reached 5.2% w/w (moisture average value). Sodium silicate solution was supplied by Jordanian Pharmaceutical Manufacturing (JPM, Jordan). Pure magnesium silicate (99.9%) was supplied by an Indian company. 2.3 Preparation of powders 2.3.1 Magnesium silicate (MgSiO 3 ) powder Magnesium silicate was prepared by mixing sodium silicate solution with Dead Sea water, followed by washing for several times with deionized water until the ph reached 8-9. Next, the precipitate (MgSiO 3 ) was dried in an oven at 115-120 C for 24 hours. After that, the dried magnesium silicate was crushed and sieved until it became a soft powder that matched the particle size of maize starch. 2.3.2 Mixed dry powder The powder of magnesium silicate and starch were dried in an oven until the moisture content was less than 8% w/w. Magnesium silicate-starch mixtures were prepared with different concentrations of 5, 10, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80 and 90 % w/w magnesium silicate and were gently mixed for 20 minutes. 2.3.3 Dry granulation of mixed powders ISBN: 978-1-61804-137-1 59

This was prepared by using roller compactor with constant roll and screw speed at different compaction pressure. Two methods were used; these are described below. First method: The speed of both the screw and roll after trial and error were set to about 18.8 and 4.23 rpm, respectively. The pure magnesium silicate was fed into the screw of the compactor into the DP pressure rolls at different compaction pressures of 2, 4, 5, 6, 7, 8, and 9 MPa. The DP is designed to provide a uniform distribution of force to the powder, creating a consistent ribbon of pure magnesium. It is important to mention that pure maize starch could not be compacted. Two kilogram of starch-magnesium silicate mixtures at different concentrations, namely 10, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, and 90% w/w magnesium silicate were fed to the screw, each sample alone at given compaction pressures. Samples from each system of starch- magnesium silicate were taken for analysis. All the resulting ribbons or flakes of the samples were sieved on 18/inch size fraction to get the granules. Second method: For each starch-magnesium silicate system at given concentration, namely 20, 30, 40, 50, 60, 70, 80, and 90% w/w magnesium silicate, 2 kg of sample was granulated in the dry granulation/ roller compactor at given compaction pressures of 4, 5, 6, 7, 8 MPa for second and third time of dry granulation and also for pure magnesium silicate. 2.4 Bulk density measurement The bulk density (g/ml) was determined for each sample. In this case a graduated cylinder of 100 ml was maintained on the weighting balance, and then filled up with the powder samples carefully to the rim using a spoon. Then the weight of the powder sample was recorded (W s ) for each sample. The bulk density is then calculated using: where ρ B is the bulk density (g/ml), m S is the mass of powder sample (g). 2.5 Permeability test of excipient Ten grams of each powder sample were transferred into the biorad tube; replicates of eight samples were considered for each system. The first height of the powder bed sample was recorded as H 0 ; then deionized water was added up to 20 cm. The biorad tube was shaken manually for 20 minutes. Deionized water was added quickly up to 45 cm, and then the powder was left to sediment for 8 hours. The powder bed height after sedimentation was recorded as H 1. After that, the cap of the tube was removed and deionized water was allowed to flow through the powder bed. The first 10 ml were returned back to the hydraulic head and the powder head height was recorded again as H 2. The time was recorded for each 10 ml of deionized water until it reached a constant rate. The level of deionized water in the tube was fixed to retain the hydraulic pressure constant during the test. 2.6 Swelling capacity test Ten grams of each sample was transferred into a measuring cylinder, followed by addition of distilled water up to 45 ml. The measuring cylinder was shacked continuously for 15 minutes, and then the samples were left to precipitate for 8 hours at room temperature. The swelling capacity was calculated using: where V f is the final volume of swollen samples after 8 hours (ml), V i is the initial volume of sample in the measuring cylinder (ml). 2.7 Tablets preparation and properties measurements The tablet is most popular dosage form in pharmaceutical industry. It consists of a mixture of active and excipient material in powder form. In this study, the excipient (mixture of starch-magnesium silicate) was used alone to prepare tablet for disintegration measurement purpose. Part of each sample (starch-magnesium silicate) with 20 and 30 % w/w magnesium silicate was taken for compression in a single punch tablet compression instrument at 8 ton with a fixed weight of one gram, and with 11 inch punch circular. The resulting tablets were tested to ISBN: 978-1-61804-137-1 60

determine their physical properties. These include weight variation, hardness, and disintegration. The test for weight variation showed the tablet weight uniformity, where 10 tablets were weighed individually using analytical balance, the mean weight of these tablets was taken. The hardness test was applied to determine the strength of tablet crushing, where 10 tablets of each sample were maintained individually inside the hardness tester. The disintegration test was used to determine the disintegration time or the resistance of tablet to break down into particles. 3 Results and Discussion Properties of maize starch, pure MgSiO 3 and starch-mgsio 3 mixture The Darcy s law was used for interpreting the results obtained. This was accomplished, for example, for pure magnesium silicate at 4 MPa which resulted in permeability (K) value of 4.17 10-3 cm/sec with swelling capacity equal to zero percentage. The bulk density for maize starch is 0.50 g/cm 3, for pure magnesium silicate prepared in the laboratory it was measured as 0.71 g/cm 3, while for synthetic magnesium silicate the bulk density is 0.88 g/cm 3. The bulk density for the starchmagnesium silicate mixture is in the ranges (0.66-0.68 g/cm 3 ) after the granulation process. The bulk density for starch-mgsio 3 compacted mixture increased with increasing MgSiO 3 concentration, since maize starch bulk density was 0.50 g/cm 3, for synthetic pure MgSiO 3 the bulk density was 0.88 g/cm 3, while for 20% and 90% MgSiO 3 granules it was is 0.65 and 0.85, respectively. Maize starch showed the lowest permeability value of 1.1 10-4 cm/sec. This could be due to a narrow particle size distribution of maize starch, which acts as a hydrophilic powder. However, for pure MgSiO 3 (without compact granulation) the permeability increased to a value of 55.3 10-4 cm/sec, which could be due to the open area which may allow water to flow through. Fig. 1 refers to the permeability value of starch-mgsio 3 mixture at different concentration of MgSiO 3 before dry granulation/roller compactor. It is seen that permeability increases with the increase in MgSiO 3 concentration. At high concentration of MgSiO 3, magnesium silicate becomes more dominant in the mixture, which means that the contribution of starch to mixture properties is lower, and thus starch gelatinization behavior diminishes. Also, permeability values of each of the prepared MgSiO 3 and the synthetic one are close to each other; 55.3 10-4 and 59.8 10-4 cm/sec, respectively. Effect of compaction pressure Figure 2 demonstrates that the increase in compaction pressure of the dry granulation roll compactor can cause an increase in the permeability. Fig. 1: Effect of MgSiO 3 concentration on permeability of co-excipient using starch- MgSiO 3 mixture without granulation. ISBN: 978-1-61804-137-1 61

Fig. 2: Effect of compaction pressure on permeability of pure MgSiO 3 using 18/inch mesh sieve. Pure MgSiO 3 showed an increase in permeability with an increase in compaction pressure of roll compactor at different levels of granulation, as shown in Fig. 4. The first granulation level prevail the highest permeability value at 9 MPa, followed by the second and third granulation level, respectively. At same compaction pressure, such trend may be explained in terms of fine particles, which decrease continuously with increase in the number of dry granulations roll compaction cycle (granulation level) and thus providing more area for water to penetrate through. Figure 3 shows that the permeability value increases with the increase in compaction pressure at different MgSiO 3 concentration. At 50% w/w MgSiO 3, the highest value of permeability is achieved. This could be due to the production of granules at high pressure which results in a decrease in fine particles. Fig. 4: Effect of compaction pressure on permeability of co-excipient using pure MgSiO 3 and 18/inch mesh sieve at different granulation levels; level one; level two, level three Fig. 3: Effect of compaction pressure on permeability of starch- MgSiO 3 co-excipient at different MgSiO 3 concentrations using 18/inch mesh sieve. MgSiO 3 concentration (w/w): 20%; 25%, 30%; 35%; 40%; 50%. It also appears that granulation level of different compaction forces and different MgSiO 3 concentration influences the permeability of the excipient. These effects are presented in Figs. 5 7, where permeability increases with increase in compaction force and MgSiO 3 concentration followed by different behavior of each granulation level. It is obvious that the fine particle decreases with increasing in granulation level; in which these fine particles block the porous and prevent water to flow through it. ISBN: 978-1-61804-137-1 62

Fig. 5: Effect of compaction pressure on permeability of co-excipient at first granulation level using starch-mgsio 3 mixture with different MgSiO 3 concentrations (w/w MgSiO 3 ): 40%; 50%, 60%; 70%; 80%; 90% Fig. 7: Effect of compaction pressure on permeability of co-excipient using starch- MgSiO 3 mixture for the third granulation level with different MgSiO 3 concentrations (% w/w MgSiO 3 ) using 18/inch mesh sieve: 40%; 50%, 60%; 70%; 80%; 90 Fig. 6: Effect of compaction pressure on permeability of co-excipient at second granulation level using starch-mgsio 3 mixture with different MgSiO 3 concentrations (w/w MgSiO 3 ) using 18/inch mesh sieve: 40%; 50%, 60%; 70%; 80%; 90%. Figure 8 shows an increase in permeability of starch-mgsio 3 at 40% w/w MgSiO 3 at different granulation levels. At first granulation level, the permeability increases with the increase in compaction pressure to a certain compaction pressure (7 MPa) and beyond this pressure second granulation level dominates first granulation level; while third granulation level shows the lowest permeability. Also, starch-mgsio 3 at 50%w/w MgSiO 3 have the same behavior but at another compaction pressure (at 6.5 MPa) as illustrated in Fig. 9. It could be assumed that there is an overlap between the influence of particle size and surface area at the same concentration of MgSiO 3 at both first and second granulation levels. ISBN: 978-1-61804-137-1 63

Fig. 8: Effect of compaction pressure on permeability of co-excipient using starch- MgSiO 3 mixture of 40% w/w MgSiO 3 using 18/inch mesh sieve with different granulation levels; level one; level two, level three. second and third granulation level, respectively. The three figures demonstrate that co-excipient at 60% w/w MgSiO 3 showed highest permeability value followed by 50% and 40% w/w MgSiO 3. This increase in permeability is due to the elimination of fine particles present in the sample, which in turns increases the voids between the particles and thus allowing water to penetrate through easily. In addition, Fig. 13 present permeability results using 20% and 30% MgSiO 3 of (w/w) at different granulation level. It is seen that system at 30% MgSiO 3 for third granulation level showed the highest permeability value, followed by 20% MgSiO 3 for third granulation level until it reach 20% MgSiO 3 for first granulation level of the lowest value. This suggests that there are different factors affecting the permeability of the co-excipient depending on both concentration of MgSiO 3 and granulation level. Fig. 9: Effect of compaction pressure on permeability of co-excipient using starch- MgSiO 3 mixture of 50% w/w MgSiO 3 using 18/inch mesh sieve with different granulation levels; level one; level two, level three. Certain starch-mgsio 3 samples at given MgSiO 3 concentration and compaction pressure passed through 18/inch mesh sieve and collected on 22/inch mesh sieve in a purpose to remove fine particles. The permeability of these samples was measured and it was noticed that the permeability increased with an increase in compaction pressure for all concentrations at different granulation levels; such results are presented in Figs. 10, 11, and 12 for first, Fig. 10: Effect of compaction pressure on permeability of co-excipient for the first granulation level using starch-mgsio 3 mixture using 18-22/ inch mesh sieve with different MgSiO 3 concentrations (w/w MgSiO 3 ): 40%; 50%, 60% ISBN: 978-1-61804-137-1 64

Fig. 11: Effect of compaction pressure on permeability of co-excipient for the second granulation level using starch-mgsio 3 mixture using 18-22/ inch mesh sieve with different MgSiO 3 concentrations (w/w MgSiO 3 ): 40%; 50%, 60%. Fig. 12: Effect of compaction pressure on permeability of excipient for the third granulation level using starch-mgsio 3 mixture using 18-22/ inch mesh sieve with different MgSiO 3 concentrations (w/w MgSiO 3 ): 40%; 50%, 60%. Fig. 13: Effect of compaction pressure on permeability of co-excipient for different granulation levels using starch-mgsio 3 mixture with different MgSiO 3 concentrations (w/w MgSiO 3 ) using 18/inch mesh sieve: first granulation level of 30%; first granulation level of 20%, second granulation level of 30% w/w MgSiO 3 ; second granulation level of 20%; third granulation level of 30%; third granulation level of 20% Swell capacity Swelling capacity was calculated for each sample for both physical mixtures: starch- MgSiO 3 (before granulation process/ roll compacted) and granulated/roll compacted starch-mgsio 3 mixture of 18/inch mesh sieve. These are presented in Figures 14 and 15; it is seen that swelling capacity decreases with an increase in MgSiO 3 content. As MgSiO 3 dominating the content, the swell behavior of starch begin to decrease with increase in magnesium silicate content. However, the trend is a bit different when using granulated samples since swelling capacity of starch-mgsio 3 mixture decreases with the increase in MgSiO 3 content up to certain level and then it increases with MgSiO 3 content (Figure 13). This is because of pure MgSiO 3 which did not show any swell behavior (i.e. swell capacity is zero%). On the other hand, pure maize starch favors absorption of water and thus it showed the highest swell value of 125%. It was also noticed that compaction pressure for systems ISBN: 978-1-61804-137-1 65

with different concentrations of MgSiO 3 does not have a large effect on swelling behavior. Figure 14: Swelling capacity versus MgSiO 3 concentration for granulated and un-granulated mixture of starch-mgsio 3 : un-granulated starch-mgsio 3 ; granulated starch-mgsio 3. pressure and granulation levels. It is seen that sample of 30% MgSiO 3 at third granulation level showed the fast disintegration time followed by sample of 20% MgSiO 3 at third granulation level, 30% MgSiO 3 at second granulation level, 30% MgSiO 3 at first granulation level, 20% MgSiO 3 at second granulation level, and finally 20% MgSiO 3 at first granulation level which showed the lowest disintegration time. The molecules of starch absorb water easily, which qualify it to swell more rapidly with decreasing MgSiO 3 and break the bonding between the molecules; this leads to longer disintegration time. When MgSiO 3 concentration increases, the disintegration time starts to decrease and swell capacity increases. Less swelling sample has fast disintegration due to capillary action/porosity, which provides pathways for the penetration of fluid/water into the tablet. Fluid drawn up into pathways and rupture interparticulate bond causing tablet to break apart. Fig. 15: Swelling capacity versus MgSiO 3 concentration of granulated starch-mgsio 3. Disintegration time, hardness and weight variation of uncoated tablet Tablet physical tests including disintegration time, hardness and weight variation were applied on 20% and 30% of MgSiO 3 samples sieved on 18/inch mesh sieve. The results showed that all tablet weight variations at different conditions were within 32.76 to 34.50 %. Figure 16 shows disintegration time of uncoated and un-active tablet for 20% and 30% (w/w) MgSiO 3 samples at different compaction Fig. 16: Effect of compaction pressure on the tablet disintegration time with different granulation level for two MgSiO 3 concentration (w/w MgSiO 3 ): first granulation level of 20%; second granulation level of 20%; third granulation level of 20%; first granulation level of 30%; second granulation level of 30%; third granulation level of 30% Tablet hardness is an indicator of tablet strength dependence on the strength of internal bonding of the tablet granules. Tablet hardness was measured for the some samples as shown ISBN: 978-1-61804-137-1 66

Fig. 17. It is seen that hardness increases with increasing compaction pressure of the roll compactor for both 20% and 30% of MgSiO 3 samples. At third granulation level of 30% MgSiO 3 sample at 8 MPa, the highest hardness value of 318.2 kg was achieved. Hardness increases with the increase in MgSiO 3 content at the same time having the lowest disintegration time. This is due to the low content of fine particle with increasing compaction granulation roll compactor level. Thus, when the tablet compressed under certain pressure, where these fines particles resist tablet compression, due to pore blocking and prevent the water flow, the granules are easily compacted with good tablet hardness. canals through the combined mixture, and thus development of meso- and microporous structure. The dry granulation roll compaction level also affects the surface area. For pure MgSiO 3 at first dry granulation level of roll compactor, the heights BET surface area of 192.19 m 2 /g was obtained. While at third granulation level of 30% w/w MgSiO 3, the lowest BET surface area of 5.65 m 2 /g was obtained. Maize starch has the lowest BET surface area of 0.58 m 2 /g. Table 1: BET analysis of different MgSiO 3 systems at 8 MPa compaction pressure of different dry granulation roll compaction level. Dry granulation roll compaction pressure at 8 MPa Pure MgSiO 3 (100%) BET surface area First granulation level Third granulation level 192.19 m 2 /g 147.40 m 2 /g 30% MgSiO 3 50.11 m 2 /g 5.65 m 2 /g Fig. 17: Effect of compaction pressure of different granulation level on tablet hardness with different concentration of MgSiO 3 (w/w MgSiO 3 ): first granulation level of 20%; second granulation level of 20%, third granulation level of 20% w/w MgSiO 3 ; first granulation level of 30%; second granulation level of 30%; third granulation level of 30%. Effect of concentration and compaction pressure on the surface area The specific surface area measurements were obtained by means of the Brunauer- Emmet-Teller (BET) method using NOVA-200 instrument. BET measurements showed that surface area of the exepients samples increases with the increase in MgSiO 3 concentration of mixture of starch-mgsio 3 (Table 1). MgSiO 3 has catalytic action due to possible opening of 90% MgSiO 3 174.63 m 2 /g 128.78 m 2 /g Thus, it can be deduced that at low concentration of MgSiO 3 of 30% MgSiO 3 at third granulation roll compaction level, the permeability is higher than that at first granulation level. This is due to the influence of particle size diameter at this level of MgSiO 3 (30%w/w). While for 90% MgSiO 3 the surface area affect the permeability more than particle size of this sample. The particle size diameter was measured using Mastersizer and results are shown in Table 2 for different samples, where d(0.1), for example, represents the particle diameter at which 10% of the distribution is below. Permeability, as an indicator of disintegration, is affected by particle size. As known, the porosity increases with larger particle size of high MgSiO 3 concentration of ISBN: 978-1-61804-137-1 67

starch-mgsio 3 mixture which lead to lower swelling then to fast disintegration. The bonding formation between the starch-mgsio 3 mixture particles with dry granulation roll compaction sufficiently become strong, and thus prevents breakdown of the granules. Increase in the compaction pressure of the dry granulation improves contact area and also the strength of the bonding as a result of increasing Van der Waals force with interparticulate distance reducing. This is an important result for the effect of dry granulation roll compaction level on specific surface area of excipient as, although not in our case, less surface area will be available for any drug adsorption. Table 2: Particle size distribution of different MgSiO 3 systems MgSiO 3 Sample Particle Size Diameter (µm) d (0.1) d (0.5) d (0.9) d (0.1) d (0.5) d (0.9) 30% MgSiO 3 not compacted 5.10 12.674 30.94 ------ 90% MgSiO 3 not compacted 5.16 12.723 31.40 ------ Pure Maize Starch (100%) 8.21 13.01 19.10 ------ Granulation roll compaction at Pressure at 8 MPa First level Third level 30% MgSiO 3 compacted 4.72 13.39 111.24 8.93 267.93 964.71 90% MgSiO 3 compacted 6.71 14.70 316.97 7.57 388.82 1018.45 4 Conclusion The work performed herein represents a continuous investigation on a novel multifunctional excipient developed recently from starch compacted with magnesium silicate. The previously impressive scientific data provided on the good binding and fast disintegration of that excipient was found to lack mechanistic understanding on the disintegration of starch compacted with magnesium silicate. Therefore, the present study was designed to obtain an improved understanding on tablets disintegration by the application of the concept of permeability on a mixture of starch with magnesium silicate subjected to multi-compaction steps using the roll compactor. The results indicate that the permeability of starch is directly proportional to the applied compaction pressure and to the amount of magnesium silicate blended with starch. Moreover, permeability was found to be dependent, to a great extent, on the particle size distribution of the compacted granules and this may imply on the voids between the particles. Such dependency renders a remarkable low permeability values obtained when the mixture contains some degree of fine particles present beside the coarser ones. A better understanding to the effect of particle size distribution, magnesium silicate content, and number of compaction cycles on permeability was brought into surface when the specific surface areas of the compacts were measured. It is clear that the higher the number of compaction cycles, the lower the number of fine granules present and the lower the available particles specific surface area which in turn increases the permeability values. These findings will enable effective control of the excipients functional behavior during processing as well as in the development of compacted starch-mg silicate products in the pharmaceutical field. References: ISBN: 978-1-61804-137-1 68

[1] United states Pharmacopeia and national formuary (USP30-NF25: Vol.1, p.664). Rockville, MD: US Pharmacopoeia Convention, 2007. [2] I. Rashid, M. Al-Remawi, A. Efttaiha, and A. Badwan, Chitin-silicon dioxide co-precipitate as a novel superdisintegrant. Journal of Pharm. Sci., 97 (11), 2008, pp. 4955-4969. [3] N. Zhao, L. Augsburger, The influence of granulation on superdisintegrant performance. Pharm. Dev. Technol, 11(1), 2006, pp. 47-53. [4] A. Badwan, M. Al-Remawi, (2007). Chitosan-silicon dioxide corprecipitate as an excipient in solid dosage forms. Eur. Pat. Appl., 23. Jordan: The Jordanian Pharmaceutical Manufacturing Co. [5] I. Rashid, N. Daraghmeh, M. Al- Remawi, S. Leharne, B. Chowdhry, A. Badwan, Characterization of Chitin- Metal Silicate as Binding superdisintegrants. Journal of Pharm. Sci., 98 (12), 2009, pp. 4887-4901. ISBN: 978-1-61804-137-1 69