Investigation of Ethylcellulose as a Matrix Former and a New Method to Regard and Evaluate the Compaction Data

Three types of ethylcellulose—having different molecular weights, i.e., different viscosity grades (7, 22, 50 cP)-were used for our polymer compression tests for the production of matrix tablets. The production methods used were direct compression and wet granulation. We tested the compactability, the compressibility, and the energy involved in compaction by the use of F-D curves and the controlled drug release from the ethylcellulose matrix tablets using the above-mentioned methods. A lower viscosity grade in ethylcellulose is more compressible than the higher grade. Wet-granulated ethylcellulose also shows a better compactibility than directly compressed ethylcellulose. Our investigation indicates also that the dissolution rates are indirectly proportional to the hardness of the tablets. Furthermore, wet-granulated tablets produce a more rapid drug release than those which are directly compressed.     

Investigation of Ethylcellulose as a Matrix Former and a New Method to Regard and Evaluate the Compaction Data

Abstract

Three types of ethylcellulose—having different molecular weights, i.e., different viscosity grades (7, 22, 50 cP)-were used for our polymer compression tests for the production of matrix tablets. The production methods used were direct compression and wet granulation. We tested the compactability, the compressibility, and the energy involved in compaction by the use of F-D curves and the controlled drug release from the ethylcellulose matrix tablets using the above-mentioned methods. A lower viscosity grade in ethylcellulose is more compressible than the higher grade. Wet-granulated ethylcellulose also shows a better compactibility than directly compressed ethylcellulose. Our investigation indicates also that the dissolution rates are indirectly proportional to the hardness of the tablets. Furthermore, wet-granulated tablets produce a more rapid drug release than those which are directly compressed.     

Comparison of Moisture-Activated Dry Granulation Profess with Conventional Granulation Methods for Sematilide Hydrochloride Tablets

During the development of a tablet formulation of a cohesive, fluffy investigational drug, a novel moisture-activated dry granulation (MADG) process was studied in comparison with two conventional granulation methods, i.e., wet granulation and dry granulation with a roller compactor, as well as with a direct compression formulation method. The MADG method produced granules with excellent flowability which were equivalent in a number of ways to those produced by either conventional wet granulation or dry granulation methods and which were much better than the powder blend from the direct compression formulation. The tablets prepared using the MADG method had better content uniformity than those made using material from wet and dry granulation processes. Other tablet properties, such as weight variation, friability and dissolution, were similar among the tablets produced by the four processes     

The Tabletting Properties of Dika Fat Lubricant

The lubricant property of dika fat, a solid vegetable oil extracted from the kernels of Irvingiaqabonensis var gabonensis and var excelsia was investigated. An instrumented tablet machine (ITM) was used to evaluate the effect of dika fat on the unit ejection force (EJF/A) of a model direct compression formulation. Dika fat, at equivalent concentration levels, performed better than magnesium stearate, stearic acid and a hydrogenated vegetable oil STEROTEX, in reducing EJF/A of tablets compressed from the model direct compression formulation. Dika fat imparted no adverse effect on the hardness, disintegration and dissolution of directly compressed hydrochlorothiazide tablets prepared in this study.     

Characterization of the tableting properties of β-cyclodextrin and the effects of processing variables on inclusion complex formation, compactibility and dissolution

The tableting properties of a number of commercially available β-cyclodextrins were characterized. Fluidity was insufficient for routine direct compression. Compactibility varied by source but was excellent. Lubrication requirements were minimal. An inclusion complex of β-cyclodextrin/Progesterone was formed and the tableting properties of the complex were compared to those of a physical mixture in both directly compressed and wet granulated products. Inclusion complexes spontaneously formed during wet granulation processing. Substantial differences in tableting properties were found as processing variables were changed. β-cyclodextrin exhibits considerable promise as a standard filler binder in tableting.     

Characterization of the tableting properties of β-cyclodextrin and the effects of processing variables on inclusion complex formation,compactibility and dissolution

Abstract

The tableting properties of a number of commercially available β-cyclodextrins were characterized. Fluidity was insufficient for routine direct compression. Compactibility varied by source but was excellent. Lubrication requirements were minimal. An inclusion complex of β-cyclodextrin/Progesterone was formed and the tableting properties of the complex were compared to those of a physical mixture in both directly compressed and wet granulated products. Inclusion complexes spontaneously formed during wet granulation processing. Substantial differences in tableting properties were found as processing variables were changed. β-cyclodextrin exhibits considerable promise as a standard filler binder in tableting.     

Effects of manufacturing process variables on in vitro dissolution characteristics of extended-release tablets formulated with hydroxypropyl methylcellulose

The purpose of this study was to investigate the effect of three process variables: distribution of hydroxypropyl methylcellulose (HPMC) within the tablet matrix, amount of water for granulation, and tablet hardness on drug release from the hydrophilic matrix tablets. Tablets were made both by direct compression as well as wet granulation method. Three formulations were made by wet granulation, all three having the exact same composition but differing in intragranular:intergranular HPMC distribution in the matrix. Further, each formulation was made using two different amounts of water for granulation. All tablets were then compressed at two hardness levels. Dissolution studies were performed on all tablets using USP dissolution apparatus I (basket). The dissolution parameters obtained were statistically analyzed using a multilevel factorial-design approach to study the influence of the various process variables on drug release from the tablets. Results indicated that a change in the manufacturing process could yield significantly dissimilar dissolution profiles for the same formulation, especially at low-hardness level. Overgranulation could lead to tablets showing hardness-dependent drug-release characteristics. Studies showed that intergranular addition of a partial amount of HPMC (i.e., HPMC addition outside of granules) provided a significant advantage in making the formulation more robust over intragranular addition (i.e., that in which the entire amount of HPMC was added to the granules). Dissolution profiles obtained for these tablets were relatively less dependent on tablet hardness irrespective of the amount of water added during granulation.     

Formulation of Griseofulvin Tablets

Abstract

Difficulties in the formulation of griseofulvin tablets are reviewed. A number of griseofulvin direct compression, pre-compression and polyvinylpyrrolidone granulated tablet formulation have been successfully produced and evaluated, in all cases a mixture of dicalcium phosphate dihydrate and calcium phosphato-carbonate complex was used as tablet matrix. Attempts to use other direct compression tablet matrices proved unsuccessful. The tablets produced have been compared with two commercially available products and the data obtained indicated that the formulations developed in this study have potential for further exploitation.     

Tablet-to-Tablet Dissolution Variability and its Relationship to the Homogeneity of a Water Soluble Drug

The homogeneity of a water soluble drug in a tablet granulation was studied by mixing the granulated drug with excipients in a V-shaped tumbling mixer. Samples were withdrawn from five different locations of the mixer for homogeneity and dissolution studies at different mixing times. For dissolution studies, tablets were compressed at a constant compression load. Qualitatively, the coefficient of variation of mixing and dissolution looked similar, suggesting that the mixing homogeneity may have some relationship to the tablet-to-tablet dissolution variability. The addition of magnesium stearate resulted in an increase in the coefficient of variation of mixing and a decrease in the dissolution rate. A large decrease in the dissolution rate occured during the first minute of mixing with the magnesium stearate. The tablet crushing strength continuously decreased during the first 10 minutes of mixing with the magnesium stearate. The results suggested that the formulation in which a major portion of the excipients was not wet granulated with the drug resulted in higher tablet-to-tablet dissolution variability. The addition of sodium starch glycolate or sodium carboxymethyl cellulose to starch for enhancing disintegration neither improved the tablet-to-tablet dissolution variability nor increased the rate of drug dissolution.     

The Tabletting Properties of Dika Fat Lubricant

Abstract

The lubricant property of dika fat, a solid vegetable oil extracted from the kernels of Irvingiaqabonensis var gabonensis and var excelsia was investigated. An instrumented tablet machine (ITM) was used to evaluate the effect of dika fat on the unit ejection force (EJF/A) of a model direct compression formulation. Dika fat, at equivalent concentration levels, performed better than magnesium stearate, stearic acid and a hydrogenated vegetable oil STEROTEX, in reducing EJF/A of tablets compressed from the model direct compression formulation. Dika fat imparted no adverse effect on the hardness, disintegration and dissolution of directly compressed hydrochlorothiazide tablets prepared in this study.     

Characterization of excipient and tableting factors that influence folic acid dissolution, friability, and breaking strength of oil- and water-soluble multivitamin with minerals tablets

The goal of this study is to characterize the formulation and processing factors that influence folic acid dissolution from oil- and water-soluble multivitamin with minerals tablet formulations for direct compression. The following parameters were studied: bulk filler solubility, soluble to insoluble bulk filler ratio, triturating agent (preblending carrier) solubility, disintegrant usage, compression pressure, and folic acid particle size. Folic acid particle size was determined by using light microscopy, and surface area was measured by using BET adsorption. The tablets were compressed on an instrumented Stokes B2 tablet press, and the friability, weight variation, and dissolution were measured according to USP methods, along with tablet breaking strength. In summary, we found the following factors to be critical to folic acid dissolution: bulk filler solubility (soluble fillers, such as maltose, increase folic acid dissolution); disintegrant amount (levels less than 0.4% (w/w) are ineffectual, whereas levels greater than 1.2% (w/w) did not further increase dissolution); and compression force (generally, maltose produce harder tablets). In addition, folic acid dissolution was less affected by changes in compaction pressure when a “super” disintegrant and maltose, as a bulk filler, were used. It was determined that the trituration agent did not play a significant role in folic acid dissolution. In the range of parameters studied, statistical analysis found no significant interactions between the parameters studied, which means they act independently in an additive manner. The results also show that no one factor is completely responsible for dissolution failure. Thus, it is the combination of formulation factors and processing conditions that collectively add up to produce dissolution failure; however, the use of a disintegrant and a soluble filler such as maltose can make a formulation more robust to the inevitable changes that can occur during commercial production.     

A Contribution to the Manufacture of Diiodoquin TABLETS by Direct Compression

Six direct compression vehicles and their binary blends in ratios of 1:1, 1:3 and 3:1 were investigated to compress diiodoquin directly into tablets. With respect to the mechanical properties of the produced tablets, Avicel, Celutab and 5TAR-x1500 were the suitable single vehicles for the manufacturing. Five vehicles, except STAR-x1500, produced tablets of fairly long disintegration times (120 min), while the other vehicle could not compress diiodoquin. The results shewed that blending of Avicel or Celutab with STAR-x1500 improved the physical standards of the produced tablets. Other than being a powerful disintegrant, STAR-x1500 could recover the disintegrating effect of Avicel. On the other hand, the reduction in disintegration times of the tablets compressed with STAR-/Celutab blends, was due to the incorporation of STAR-x in the formulations.

In such a case of noncompressible drug, a large concentration of a binary blended vehicle was needed to compress tablets of good physical characters. The least concentration needed to compress diiodoquin into tablets was not less than 42.0% w/w.     

A Contribution to the Manufacture of Diiodoquin TABLETS by Direct Compression

Abstract

Six direct compression vehicles and their binary blends in ratios of 1:1, 1:3 and 3:1 were investigated to compress diiodoquin directly into tablets. With respect to the mechanical properties of the produced tablets, Avicel, Celutab and 5TAR-x1500 were the suitable single vehicles for the manufacturing. Five vehicles, except STAR-x1500, produced tablets of fairly long disintegration times (120 min), while the other vehicle could not compress diiodoquin. The results shewed that blending of Avicel or Celutab with STAR-x1500 improved the physical standards of the produced tablets. Other than being a powerful disintegrant, STAR-x1500 could recover the disintegrating effect of Avicel. On the other hand, the reduction in disintegration times of the tablets compressed with STAR-/Celutab blends, was due to the incorporation of STAR-x in the formulations.

In such a case of noncompressible drug, a large concentration of a binary blended vehicle was needed to compress tablets of good physical characters. The least concentration needed to compress diiodoquin into tablets was not less than 42.0% w/w.     

Formulation and Evaluation of Paracetamol 500 G Tablets Produced by a New Direct Cranulation Method

Currendy there are three general methods available for producing tablets. These methods are (a) direct compression, (b) double compression or slugging, and (c) wet granulation. The simplest method is direct compression, since the drug need only be mixed with a suitable free flowing exeipieut and compressed directly into tablets. The process has obvious advantages since the use of a binding agent is avoided and no drying at all is required. As a result it can be used to tablet hydrolysable and theroolabile drugs. Even though it does have many advantages, it also has limitations concerning capacity, colouration and segregation. Perhaps the most serious disadvantage is the segregation of components during handling. no further lubricant was added since the granules were effectively self-lubricating. Compression of the granules was effected on a Maneaty F3 instrumented machine between J “punches at 47, 102 and 215 MNm”². 20 tablets from each batch were individually weighed and the mean, the standard deviation, and the coefficient of variation evaluated.     

The Effect of the Wet Granulation Process on Drug Dissolution

Abstract

Wet granulation can be an important processing step for pharmaceutical solid dosage forms. In this investigation emphasis was directed towards the influence of a “simple” wet granulation process on drug release from granules and their resulting tablets. Direct compression blends of the same materials were used as controls. Binary mixtures containing a 5% level of either theophylline, hydrochlorothiazide or chlorpheniramine maleate in microcrystalline cellulose or lactose were granulated with water. Experimentally, the powders were dry blended in a planetary mixer, wet granulated, and subsequently wet milled and dried. No dry milling step was included. Granule characterization consisted of particle size, density, porosity, compression and dissolution testing. Dissolution results varied with the drug, as expected, and dissolution at 10 minutes ranged from 35 to 95 % release. In general, however, the results indicate that dissolution from granules and the corresponding direct compression blend are similar. Although differences in compressibility were observed in the systems studied, granulation was not found to be detrimental to drug release.     

The compression of spheres coated with an aqueous ethylcellulose dispersion

Tablets were compressed from commercial samples of Sugar Spheres NF, Sucrose NF, Corn Starch NF, as well as ground spheres and a physical mixture of ground sucrose plus cornstarch. Additional tablets were compressed from spheres that had been coated with a water-soluble cellulosic polymer solution followed by an aqueous ethylcellulose dispersion. Tableting parameters measured “in-die” included work of compression, peak offset time, tablet density, and Young's modulus. Following ejection, tensile strength was determined under diametrical loading. Dissolution of a marker contained in the water-soluble layer was determined for both compressed and uncompressed spheres. Porosities at peak pressure and peak offset times or tensile strength as functions of peak pressure did not differ between tablets compressed from pristine spheres or from ground spheres. Tablets compressed from spheres had higher values for porosity, tensile strength, and peak offset time than those compressed from sucrose or the sucrose:starch mixture. Values for work of compression were higher for tablets compressed from pristine spheres or from starch. This was attributed to the work required for particle deformation and for breaking of the spheres. The greatest elastic recovery during decompression was observed for tablets compressed from pristine spheres or starch. More brittle behavior was observed for tablets compressed from sucrose or the sucrose:starch mixture. Tablets compressed from ground spheres were more brittle than those compressed from the pristine spheres, indicating an effect due to grinding. Most mechanical properties of tablets compressed from the coated spheres were comparable to those of tablets compressed from uncoated spheres. An exception was diametric strain for tablets compressed from spheres coated with the aqueous ethylcellulose dispersion. These values increased since the plasticized ethylcellulose allowed greater distortion of the tablet before failure occurred. The dye marker was released more rapidly from tablets compressed from spheres coated with the aqueous ethylcellulose dispersion than from comparable uncompressed spheres. At both the 5% and 10% coating levels, spheres coated with the aqueous ethylcellulose dispersion fused into nondisintegrating matrices during compression. Little difference in release rates was seen between the two tablets.     

Polymers with pH-dependent solubility: possibility of use in the formulation of gastroresistant and controlled-release matrix tablets

Polymers usually utilized for gastroresistant film coating of tablets or pellets such as cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT), hydroxypropylmethylcellulose phthalate (HPMCP), and Eudragit L and S were used in the preparation of drug/polymer matrix tablets. These tablets were prepared either by direct compression of both powders or by the formulation of microspheres that were then compressed. The microspheres were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffractometry analyses. Dissolution studies were finally carried out to verify if the tablets possessed gastroresistant or controlled-release characteristics. Except for Eudragit L, the polymers can be used under certain conditions in the formulation of modified-release tablets.     

The Compression of Spheres Coated with an Aqueous Ethylcellulose Dispersion

Tablets were compressed from commercial samples of Sugar Spheres NF, Sucrose NF, Corn Starch NF, as well as ground spheres and a physical mixture of ground sucrose plus cornstarch. Additional tablets were compressed from spheres that had been coated with a water-soluble cellulosic polymer solution followed by an aqueous ethylcellulose dispersion. Tableting parameters measured “in-die” included work of compression, peak offset time, tablet density, and Young's modulus. Following ejection, tensile strength was determined under diametrical loading. Dissolution of a marker contained in the water-soluble layer was determined for both compressed and uncompressed spheres. Porosities at peak pressure and peak offset times or tensile strength as functions of peak pressure did not differ between tablets compressed from pristine spheres or from ground spheres. Tablets compressed from spheres had higher values for porosity, tensile strength, and peak offset time than those compressed from sucrose or the sucrose:starch mixture. Values for work of compression were higher for tablets compressed from pristine spheres or from starch. This was attributed to the work required for particle deformation and for breaking of the spheres. The greatest elastic recovery during decompression was observed for tablets compressed from pristine spheres or starch. More brittle behavior was observed for tablets compressed from sucrose or the sucrose:starch mixture. Tablets compressed from ground spheres were more brittle than those compressed from the pristine spheres, indicating an effect due to grinding. Most mechanical properties of tablets compressed from the coated spheres were comparable to those of tablets compressed from uncoated spheres. An exception was diametric strain for tablets compressed from spheres coated with the aqueous ethylcellulose dispersion. These values increased since the plasticized ethylcellulose allowed greater distortion of the tablet before failure occurred. The dye marker was released more rapidly from tablets compressed from spheres coated with the aqueous ethylcellulose dispersion than from comparable uncompressed spheres. At both the 5% and 10% coating levels, spheres coated with the aqueous ethylcellulose dispersion fused into nondisintegrating matrices during compression. Little difference in release rates was seen between the two tablets.     

Polymers with pH-Dependent Solubility: Possibility of Use in the Formulation of Gastroresistant and Controlled-Release Matrix Tablets

Polymers usually utilized for gastroresistant film coating of tablets or pellets such as cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT), hydroxypropylmethylcellulose phthalate (HPMCP), and Eudragit L and S were used in the preparation of drug/polymer matrix tablets. These tablets were prepared either by direct compression of both powders or by the formulation of microspheres that were then compressed. The microspheres were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffractometry analyses. Dissolution studies were finally carried out to verify if the tablets possessed gastroresistant or controlled-release characteristics. Except for Eudragit L, the polymers can be used under certain conditions in the formulation of modified-release tablets.     

Effects of Temperature,Humidity, and Aging on the Disintegration and Dissolution of Acetaminophen Tablets

Abstract

The effect of storage for 8 weeks at 40°C in moderate and high humidity on acetaminophen tablets prepared by the wet granulation method using povidone or pregelatinized starch as a binder was studies. Storage at 52% relative humidity produced an increase in hardness of acetaminophen tablets and storage at 94% relative humidity caused a decrease in hardness. In all cases tablets granulated with pregelatinized starch were less susceptible to change caused by humidity than tablets granulated with povidone. The disintegration of tablets containing starch or povidone was slowed as the humidity was increased. Tablets stored at 40 =C and 94 V. relative humidity showed a substantial slowing of dissolution, but there was little change of dissolution of tablets when aged at 40 -C / 52% relative humidity. In comparing starch and povidone as binders, acetaminophen tablets prepared with pregelatinized starch were less effected by high humidity than tablets prepared with povidone.