In the pharmaceutical industry uniform flow of powders is one of the most important considerations in solid dosage manufacture. Improper feeding of powders from storage hoppers into dye-presses can lead to inconsistent product quality, causing economic and health impacts. Investigation into the properties affecting powder flow is crucial. There were four objectives of the current research: 1. To determine the effect of moisture on the flow (Jenike flow index, Hausner Ratio and Carr Index, static and dynamic angle of repose) of selected pharmaceutical powders. 2. To study the effect of particle shape and size on Jenike flow index for selected starch and pharmaceutical powders. 3. To determine the effect of mixture compositions on the Jenike flow index of ordered mixtures of selected pharmaceutical powders. 4. To develop a novel flowability tester based on electrical capacitance tomography (ECT) that measures the dynamic angle of repose of powders.<p>To address the first objective, to determine the effect of moisture content on the flow of four pharmaceutical powders; an active pharmaceutical ingredient (API), aspartame, hydroxypropyl methylcellulose (HPMC), and Respitose® ML001 were selected. The API and Respitose® powders were found to be nonhygroscopic and were tested at near zero moisture contents only (in this case 0.31% and 0.19% respectively). Aspartame was tested at moisture contents of 0%, 2%, 5% and 8% and HPMC at moisture contents of 0%, 2%, 5% and 10%. Powder flowability was measured using the Jenike shear index, the Hausner Ratio, the Carr Index and the static and dynamic angles of repose. The Jenike flow index of aspartame increased from 0.885 to 3.65 with an increase in moisture content, which was attributed to the formation of large, round agglomerates. The Jenike flow index of HPMC decreased from 3.28 to 2.65 with an increase in moisture content, which was attributed to the increasing strength of liquid bridges. The Jenike flow index was the only flowability indicator to capture this complex behaviour. <p>In order to address the second objective, five starches (cow cockle, barley, rye, rice and tapioca), as well as four pharmaceutical ingredients (an API, aspartame, HPMC, and Respitose® ML001), were characterised for size and shape, and then tested for flowability. Powder flowability was measured using the Jenike shear test, the most widely accepted flowability standard in the pharmaceutical industry. It was found that the Jenike flow index decreased linearly with decreasing aspect ratio and decreasing roundness for the powders investigated. It was also determined that particle shape had a greater impact on flowability than size for powders under 30 microns in diameter. <p>To address the third objective, ordered mixtures of pharmaceutical powders were examined to determine their flowability. Six combinations of Respitose® ML001, hydroxypropyl methylcellulose (HPMC), and an active pharmaceutical ingredient (API) in varying concentrations were selected for investigation. Powder flowability was measured using the Jenike shear test, the most widely accepted flowability standard in the industry. The Jenike flow indices of the ordered mixtures were indistinguishable from the Jenike flow index of pure Respitose® at the alpha = 0.1 level.<p>The fourth objective, to develop a novel flowability tester using electrical capacitance tomography to measure the dynamic angle of repose, was investigated at the same time as the effect of moisture content. It was determined that the results of the novel dynamic angle of repose tester did not correlate well with the Jenike shear test. More development is needed before the novel flowability tester is ready for industrial use. The Jenike shear cell remains the only acceptable flow test for complex flow behaviour.

In the pharmaceutical industry uniform flow of powders is one of the most important considerations in solid dosage manufacture. Improper feeding of powders from storage hoppers into dye-presses can lead to inconsistent product quality, causing economic and health impacts. Investigation into the properties affecting powder flow is crucial. There were four objectives of the current research: 1. To determine the effect of moisture on the flow (Jenike flow index, Hausner Ratio and Carr Index, static and dynamic angle of repose) of selected pharmaceutical powders. 2. To study the effect of particle shape and size on Jenike flow index for selected starch and pharmaceutical powders. 3. To determine the effect of mixture compositions on the Jenike flow index of ordered mixtures of selected pharmaceutical powders. 4. To develop a novel flowability tester based on electrical capacitance tomography (ECT) that measures the dynamic angle of repose of powders.<p>To address the first objective, to determine the effect of moisture content on the flow of four pharmaceutical powders; an active pharmaceutical ingredient (API), aspartame, hydroxypropyl methylcellulose (HPMC), and Respitose® ML001 were selected. The API and Respitose® powders were found to be nonhygroscopic and were tested at near zero moisture contents only (in this case 0.31% and 0.19% respectively). Aspartame was tested at moisture contents of 0%, 2%, 5% and 8% and HPMC at moisture contents of 0%, 2%, 5% and 10%. Powder flowability was measured using the Jenike shear index, the Hausner Ratio, the Carr Index and the static and dynamic angles of repose. The Jenike flow index of aspartame increased from 0.885 to 3.65 with an increase in moisture content, which was attributed to the formation of large, round agglomerates. The Jenike flow index of HPMC decreased from 3.28 to 2.65 with an increase in moisture content, which was attributed to the increasing strength of liquid bridges. The Jenike flow index was the only flowability indicator to capture this complex behaviour. <p>In order to address the second objective, five starches (cow cockle, barley, rye, rice and tapioca), as well as four pharmaceutical ingredients (an API, aspartame, HPMC, and Respitose® ML001), were characterised for size and shape, and then tested for flowability. Powder flowability was measured using the Jenike shear test, the most widely accepted flowability standard in the pharmaceutical industry. It was found that the Jenike flow index decreased linearly with decreasing aspect ratio and decreasing roundness for the powders investigated. It was also determined that particle shape had a greater impact on flowability than size for powders under 30 microns in diameter. <p>To address the third objective, ordered mixtures of pharmaceutical powders were examined to determine their flowability. Six combinations of Respitose® ML001, hydroxypropyl methylcellulose (HPMC), and an active pharmaceutical ingredient (API) in varying concentrations were selected for investigation. Powder flowability was measured using the Jenike shear test, the most widely accepted flowability standard in the industry. The Jenike flow indices of the ordered mixtures were indistinguishable from the Jenike flow index of pure Respitose® at the alpha = 0.1 level.<p>The fourth objective, to develop a novel flowability tester using electrical capacitance tomography to measure the dynamic angle of repose, was investigated at the same time as the effect of moisture content. It was determined that the results of the novel dynamic angle of repose tester did not correlate well with the Jenike shear test. More development is needed before the novel flowability tester is ready for industrial use. The Jenike shear cell remains the only acceptable flow test for complex flow behaviour.

Dry powder inhalers (DPIs) are used for delivering drugs to the airways. In addition to the drug, the formulations often contain a coarse carrier, most commonly alpha lactose monohydrate. The presence of fine lactose particles in the formulation is known to improve the formulation performance. The active site, drug-fines agglomeration and increased cohesion theories have been suggested to explain improved DPI performance upon addition of fine excipient particles. This project aimed to investigate the validity of those theories. The viability of the active sites theory in explaining the improved DPI performance was investigated by studying the impact of loaded drug dose on the in vitro performance for formulation series prepared with coarse carriers with different surface characteristics. The formulations prepared with the rougher lactose carrier were seen to outperform the formulations prepared with the smoother carrier at all drug concentrations. These findings were concluded to be non-compatible with the active sites theory. The impact of addition of lactose fines with different size distributions on powder flow and fluidisation properties and in vitro performance was studied. Powder cohesion increased independent of size distribution of the fines, but did not necessarily correspond to improved performance. Therefore, the increased cohesion theory was concluded not to be the sole explanation for the improvement in DPI performance in the presence of lactose fines. Instead, the increase in performance could be preliminarily attributed to the formation of agglomerated systems. The formation and co-deposition of drug-fines agglomerates, and consequential improvement in the DPI performance was proved using morphologically directed Raman spectroscopy. The project also aimed to develop a universal model for predicting DPI performance based on the lactose properties for a wide range of carriers with different properties. No simple linear correlations between any the lactose properties and the final DPI performance were found. Therefore no single parameter can be used as a universal predictor for DPI performance. To establish more complex relationships, artificial neural networks were used for modelling the importance of different lactose properties in determining DPI performance. The proportion of fine lactose particles (<4.5 μm) was identified as the most important parameter. However, this parameter was capable of explaining only approximately half of the variation seen in the formulation performance. The current study showed that to obtain more accurate predictions for the purposes of quality-by-design approach, also other lactose properties need to be characterised.

No description available.

The primary prerequisites for powder mixtures/granules intended for tableting is to posses the quality of (i) homogenous composition; (ii) acceptable flowability, (iii) sufficient compressibility; and (iv) anti-adhesiveness. The most important prerequisite for these powder mixture/granulates is undoubtedly the ability to flow, due to its effect on product quality, especially dose and dosage form uniformity. A comprehensive literature study on the flowability of powders revealed that flow is affected by physical properties such as molecular- and interparticle forces, particle size and size distribution, particle shape, particle density, surface structure of the particle, and particle packing geometry. Various flow tests are available to determine powder flow, each measuring a variety of the properties mentioned above, resulting in different flow results and a subsequent variation in the classification of powders. Particle characterization of a wide range of pharmaceutical fillers through SEM and particle size analysis, indicated considerable differences between physical properties of the various fillers, which suggested significant differences in their flow behaviour. Flow tests were conducted determining the critical orifice diameter (COD); percentage compressibility (%C); angle of repose (AoR) and flow rate (FR) of the fillers in the absence and presence of a glidant (0.25% Aerosil® 200). The results confirmed the expected differences in flow obtained from the various tests, with no one of the fillers achieving the same flow behaviour in all the tests. The difference in flow amongst the fillers for a specific test could, to a large extent, been correlated with specific physical properties of the particles within the powder bed. COD results illustrated the influence of particle size and shape and surface structure on the flowability of these materials, with fillers with a smaller average particle size, less spherical shaped particles and uneven / rough surface structures performing poorer than their counterparts. The percentage compressibility (%C) of the materials was affected by the shape and size of the particles and the density of the materials, whilst the packing geometry also affected flow behaviour. Particles with high density and a low internal porosity tended to posses free flowing properties. Powders with a larger difference in the ratio between their respective bulk and tapped densities/volumes presented better flow results. The AoR of the fillers was affected by the cohesiveness and friction between the particles as well as the shape, surface structure and size of the particles. This method was less discriminative in terms of indicating differences in the flow of powders with comparable physical properties. A further drawback of this method was the variation in results between repetitions, which is affected by the way the samples were handled prior to measurement. The flow rate (FR) of the fillers was predominantly affected by the density of the materials and the size, shape, and surface structure of the particles. Powders with a higher density seemed to exhibit a better flow rate, although some of the other factors affected the flow rate more when the densities were very close or identical. The following general rank order for the various fillers (as an average of their performance in all the tests) were established (with no glidant present): Cellactose® 80 > FlowLac® 100 > Prosolv® HD90 * Ludipress® > Emcompress® >Avicel® PH200 > Starlac® » Emcocel® 50M * chitosan » lactose monohydrate. Addition of a glidant failed to change the rank order significantly. During the final stage of the study an attempt was made to modify and/or refine the composite flow index (CFI) proposed by Taylor ef a/. (2000:6) through (i) inclusion of flow rate results in its computation and/or (ii) varying the contribution (percentage) of each test to the CFI (Taylor & co-workers used equal contributions, namely 33 V* %, in their calculation of the CFI). The results indicated that including the results from the flow rate test was not beneficial in terms of providing a more representative CFI (in fact it reduced the accuracy of the index). Next various weight ratios for COD, %C and AoR was used to determine the CFI of each filler, and an optimum ratio was found at 50%:40%:10% (COD:%C:AoR) resulting in the highest CFI for each powder and the widest range for the CFI (largest difference between minimum and maximum values). This ratio was found in the presence and absence of a glidant. At this ratio the CFI discriminated well between the different powders in terms of their flowability. Lastly, the flowability scale for powders as used by the USP (20007:644) for %C and AoR results was adapted and fitted on the CFI results obtained for the various powders. This scale provided an exceptional fit for the powders both in the absence and presence of a glidant) and offered an excellent means for the grouping and classifcation of powders based on their CFI. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2009.

The primary prerequisites for powder mixtures/granules intended for tableting is to posses the quality of (i) homogenous composition; (ii) acceptable flowability, (iii) sufficient compressibility; and (iv) anti-adhesiveness. The most important prerequisite for these powder mixture/granulates is undoubtedly the ability to flow, due to its effect on product quality, especially dose and dosage form uniformity. A comprehensive literature study on the flowability of powders revealed that flow is affected by physical properties such as molecular- and interparticle forces, particle size and size distribution, particle shape, particle density, surface structure of the particle, and particle packing geometry. Various flow tests are available to determine powder flow, each measuring a variety of the properties mentioned above, resulting in different flow results and a subsequent variation in the classification of powders. Particle characterization of a wide range of pharmaceutical fillers through SEM and particle size analysis, indicated considerable differences between physical properties of the various fillers, which suggested significant differences in their flow behaviour. Flow tests were conducted determining the critical orifice diameter (COD); percentage compressibility (%C); angle of repose (AoR) and flow rate (FR) of the fillers in the absence and presence of a glidant (0.25% Aerosil® 200). The results confirmed the expected differences in flow obtained from the various tests, with no one of the fillers achieving the same flow behaviour in all the tests. The difference in flow amongst the fillers for a specific test could, to a large extent, been correlated with specific physical properties of the particles within the powder bed. COD results illustrated the influence of particle size and shape and surface structure on the flowability of these materials, with fillers with a smaller average particle size, less spherical shaped particles and uneven / rough surface structures performing poorer than their counterparts. The percentage compressibility (%C) of the materials was affected by the shape and size of the particles and the density of the materials, whilst the packing geometry also affected flow behaviour. Particles with high density and a low internal porosity tended to posses free flowing properties. Powders with a larger difference in the ratio between their respective bulk and tapped densities/volumes presented better flow results. The AoR of the fillers was affected by the cohesiveness and friction between the particles as well as the shape, surface structure and size of the particles. This method was less discriminative in terms of indicating differences in the flow of powders with comparable physical properties. A further drawback of this method was the variation in results between repetitions, which is affected by the way the samples were handled prior to measurement. The flow rate (FR) of the fillers was predominantly affected by the density of the materials and the size, shape, and surface structure of the particles. Powders with a higher density seemed to exhibit a better flow rate, although some of the other factors affected the flow rate more when the densities were very close or identical. The following general rank order for the various fillers (as an average of their performance in all the tests) were established (with no glidant present): Cellactose® 80 > FlowLac® 100 > Prosolv® HD90 * Ludipress® > Emcompress® >Avicel® PH200 > Starlac® » Emcocel® 50M * chitosan » lactose monohydrate. Addition of a glidant failed to change the rank order significantly. During the final stage of the study an attempt was made to modify and/or refine the composite flow index (CFI) proposed by Taylor ef a/. (2000:6) through (i) inclusion of flow rate results in its computation and/or (ii) varying the contribution (percentage) of each test to the CFI (Taylor & co-workers used equal contributions, namely 33 V* %, in their calculation of the CFI). The results indicated that including the results from the flow rate test was not beneficial in terms of providing a more representative CFI (in fact it reduced the accuracy of the index). Next various weight ratios for COD, %C and AoR was used to determine the CFI of each filler, and an optimum ratio was found at 50%:40%:10% (COD:%C:AoR) resulting in the highest CFI for each powder and the widest range for the CFI (largest difference between minimum and maximum values). This ratio was found in the presence and absence of a glidant. At this ratio the CFI discriminated well between the different powders in terms of their flowability. Lastly, the flowability scale for powders as used by the USP (20007:644) for %C and AoR results was adapted and fitted on the CFI results obtained for the various powders. This scale provided an exceptional fit for the powders both in the absence and presence of a glidant) and offered an excellent means for the grouping and classifcation of powders based on their CFI. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2009.

One of the most important prerequisites in the drug development is to attain a reproducible and robust product in terms of its nature, and its chemical and physical properties. This can be challenging, since the crystalline form of drugs and excipients can be directly transformed into the amorphous one during normal pharmaceutical processing, referred to as process-induced amorphisation or process-induced disorder. The intention of this thesis was to address the mechanisms causing disorder during powder flow and milling and, in association with this, to evaluate, the ability of Raman spectroscopy and atomic force microscopy (AFM) to quantify and characterize process-induced disorder. The amorphisation mechanisms were controlled by stress energy distribution during processing, which in turn was regulated by a series of process parameters. Compression and shearing stress caused by sliding were stress types that acted on the particles during powder flow and ball milling process. However, sliding was the most important inter-particulate contact process giving rise to amorphisation and the transformation was proposed to be caused by vitrification. The plastic stiffness and elastic stiffness of the milling-induced particles were similar to a two-state particle model, however the moisture sorption characteristics of these particles were different. Thus the milled particles could not be described solely by a two-state particle model with amorphous and crystalline domains.  Raman spectroscopy proved to be an appropriate and effective technique in the quantification of the apparent amorphous content of milled lactose powder. The disordered content below 1% could be quantified with Raman spectroscopy. AFM was a useful approach to characterize disorder on the particle surfaces. In summary, this thesis has provided insight into the mechanisms involved in process-induced amorphisation of pharmaceutical powders and presented new approaches for quantification and characterization of disordered content by Raman spectroscopy and atomic force microscopy.

Hard capsules filling machines are useful for some reasons: with them we can quick pack small quantities of powder, can make drugs for clinical trials, also can use them for students learning in university. But in literature we couldn’t find method how to count the right quantity of powder, need to fill in one capsule. For this reason, we perform some experimental works with acetylsalicylic acid, paracetamol and lactose to find out how it does right. During these works, we research how affect powder flow, powders moisture, filling condition, powder particle size to the capsules filling. Also we research is any differences between capsules position in capsules filling machine and its weight. To find is our method right, we made 3 series of acetylsalicylic acid capsules and made uniformity of content and uniformity of mass tests with them. Made accomplished fulfils European pharmacopeia’s demands.

Direct compression has gained significant interest since its advent in the late 1950's due to its potential ease compared to wet granulation. The primary prerequisites for powders used in direct compression are (i) good flow properties (ii) good compressibility and (iii) an acceptable dilution potential to accommodate a relative high percentage of active ingredient. Several filler/binders have been manufactured especially for direct compression and co–processing is one of the recent methods used to produce good compressible excipients with acceptable flow properties. In this study, lactose–based filler/binders were used which included simple and modified lactose materials (Granulac, Lactopress, Flowlac and Tablettose) as well as co–processed excipients (Starlac, Cellactose and Microcelac). A comprehensive literature study on direct compression revealed the importance of the physical properties of filler/binders such as interparticle forces, particle shape, particle size and distribution, powder density, particle surface structure and particle packing geometry which influence the flow of powders. All the materials were subjected to the various tests available to evaluate powder flow, namely (i) angle of repose (AoR), (ii) critical orifice diameter (COD), (iii) flow rate and percentage compressibility (%C) in terms of the powders' bulk and tap densities. The results of these tests confirmed the expected flow properties of the various filler/binders, with only one material exhibiting extremely poor flow properties. The following rank order in terms of all flow tests conducted was established; Starlac >> Microcelac ~ Flowlac >> Cellactose > Tablettose > Lactopress >>> Granulac. The co–processed filler/binders presented with superior flow compared to the other lactose–based materials. During the next phase of the study, the compaction properties of the various fillers were evaluated, employing direct compression. Compacts of pure filler were tabletted on an eccentric tablet press at different compression pressures (manipulated by the upper punch setting of the tablet press). The modified lactose filler/binders (Lactopress, Flowlac and Tablettose) exhibited unexpectedly poor compression profiles, where the co–processed filler/binders (Starlac, Cellactose and Microcelac) produced compacts with acceptable appearance and compact properties. Two lubricants (Mg–St or Pruv), which were tested separately in formulations were added since no compacts could be produced from the pure filler/binders. None of the modified lactose filler/binders, in combination with a lubricant, were able to produce an acceptable compact, since lamination occurred during compression. The co–processed filler/binders produced satisfactory compacts with the addition of a lubricant, but lactose–cellulose fillers (Cellactose and Microcelac) also required the inclusion of a disintegrant (Ac–Di–Sol) to induce satisfactory compact disintegration. Poor compressible active ingredients (paracetamol), which exhibit very poor flow properties, are usually difficult to use during direct compression. Many excipients (tested in this study) are formulated to accommodate these drugs and produce acceptable functional tablets. After identifying the best filler/binders (co–processed fillers), according to their flow and compressible properties, paracetamol was added to the formulations. During a pilot study, the percentage paracetamol these fillers could accommodate in a 400 mg tablet was determined. Both Microcelac and Cellactose could accommodate 24.5% w/w paracetamol, whilst Starlac could only accommodated 19.5% w/w. Paracetamol is well known for its tendency to cause tablet capping and lamination. An acceptable upper punch setting range (20–22) was chosen for tabletting, followed by quality control tests done. All three formulations produced suitable tablets for testing and exhibited good tablet properties. All tablets disintegrated within two minutes, with hardness profiles between 120 N and 148 N and friability percentages less than 1%. Dissolution studies, however, are probably the ultimate test to distinguish between the capability of filler/binders to release the optimum percentage drug after disintegration. Dissolution studies were done on all three formulations using the AUC (area under the curve) and IDR (initial drug release) as parameters to evaluate drug release. All tablets exhibited high initial dissolution rates (between 0.018 - 0.023 mg/min/ml) and 100% drug release was observed. Starlac presented with a lower amount of drug released compared to the other two, but can be explained by the lower percentage (19.5%) paracetamol present in the formulation. It was once again confirmed that the physical and compressible properties of potential directly compressible filler/binders play a major role in direct compression. It was concluded that co–processed filler/binders (Starlac, Microcelac and Cellactose) definitely exhibited better tabletting properties during direct compression. They were able to accommodate a certain percentage of paracetamol, although it was expected that they would accommodate a higher amount (at least 50% of total tablet weight). / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2011.

Direct compression has gained significant interest since its advent in the late 1950's due to its potential ease compared to wet granulation. The primary prerequisites for powders used in direct compression are (i) good flow properties (ii) good compressibility and (iii) an acceptable dilution potential to accommodate a relative high percentage of active ingredient. Several filler/binders have been manufactured especially for direct compression and co–processing is one of the recent methods used to produce good compressible excipients with acceptable flow properties. In this study, lactose–based filler/binders were used which included simple and modified lactose materials (Granulac, Lactopress, Flowlac and Tablettose) as well as co–processed excipients (Starlac, Cellactose and Microcelac). A comprehensive literature study on direct compression revealed the importance of the physical properties of filler/binders such as interparticle forces, particle shape, particle size and distribution, powder density, particle surface structure and particle packing geometry which influence the flow of powders. All the materials were subjected to the various tests available to evaluate powder flow, namely (i) angle of repose (AoR), (ii) critical orifice diameter (COD), (iii) flow rate and percentage compressibility (%C) in terms of the powders' bulk and tap densities. The results of these tests confirmed the expected flow properties of the various filler/binders, with only one material exhibiting extremely poor flow properties. The following rank order in terms of all flow tests conducted was established; Starlac >> Microcelac ~ Flowlac >> Cellactose > Tablettose > Lactopress >>> Granulac. The co–processed filler/binders presented with superior flow compared to the other lactose–based materials. During the next phase of the study, the compaction properties of the various fillers were evaluated, employing direct compression. Compacts of pure filler were tabletted on an eccentric tablet press at different compression pressures (manipulated by the upper punch setting of the tablet press). The modified lactose filler/binders (Lactopress, Flowlac and Tablettose) exhibited unexpectedly poor compression profiles, where the co–processed filler/binders (Starlac, Cellactose and Microcelac) produced compacts with acceptable appearance and compact properties. Two lubricants (Mg–St or Pruv), which were tested separately in formulations were added since no compacts could be produced from the pure filler/binders. None of the modified lactose filler/binders, in combination with a lubricant, were able to produce an acceptable compact, since lamination occurred during compression. The co–processed filler/binders produced satisfactory compacts with the addition of a lubricant, but lactose–cellulose fillers (Cellactose and Microcelac) also required the inclusion of a disintegrant (Ac–Di–Sol) to induce satisfactory compact disintegration. Poor compressible active ingredients (paracetamol), which exhibit very poor flow properties, are usually difficult to use during direct compression. Many excipients (tested in this study) are formulated to accommodate these drugs and produce acceptable functional tablets. After identifying the best filler/binders (co–processed fillers), according to their flow and compressible properties, paracetamol was added to the formulations. During a pilot study, the percentage paracetamol these fillers could accommodate in a 400 mg tablet was determined. Both Microcelac and Cellactose could accommodate 24.5% w/w paracetamol, whilst Starlac could only accommodated 19.5% w/w. Paracetamol is well known for its tendency to cause tablet capping and lamination. An acceptable upper punch setting range (20–22) was chosen for tabletting, followed by quality control tests done. All three formulations produced suitable tablets for testing and exhibited good tablet properties. All tablets disintegrated within two minutes, with hardness profiles between 120 N and 148 N and friability percentages less than 1%. Dissolution studies, however, are probably the ultimate test to distinguish between the capability of filler/binders to release the optimum percentage drug after disintegration. Dissolution studies were done on all three formulations using the AUC (area under the curve) and IDR (initial drug release) as parameters to evaluate drug release. All tablets exhibited high initial dissolution rates (between 0.018 - 0.023 mg/min/ml) and 100% drug release was observed. Starlac presented with a lower amount of drug released compared to the other two, but can be explained by the lower percentage (19.5%) paracetamol present in the formulation. It was once again confirmed that the physical and compressible properties of potential directly compressible filler/binders play a major role in direct compression. It was concluded that co–processed filler/binders (Starlac, Microcelac and Cellactose) definitely exhibited better tabletting properties during direct compression. They were able to accommodate a certain percentage of paracetamol, although it was expected that they would accommodate a higher amount (at least 50% of total tablet weight). / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2011.