Effect of Lubricants on Tensile Strengths of Tablets

The effect of concentration of lubricant on the axial and radial tensile strengths of tablets was determined for four directly compressible pharmaceutical materials: anhydrous lactose, aspirin, microcrystalline cellulose, and dibasic calcium phosphate dihydrate. The lubricants investigated were: hydrogenated vegetable oil, magnesium stearate, polyethylene glycol 4000, stearic acid, and talc. For plastic materials the tensile strengths were reduced as the concentration of the lubricant was increased. For brittle material the tensile strength was not changed significantly as the concentration of lubricant was increased.     

The Effect of Formulation on 1-131 Dissolution In Vitro from Sodium Iodide Capsules

Because of the importance of the bioavailability of 1-131 for thyroid uptake studies and thyroid therapy, the present investigation was conducted to determine the influence of diluents, type of lubricant and the concentration of lubricant on the in vitro release rate of 1-131 from 1-131 sodium iodide capsules. Formulations and 1-131 sodium iodide capsules were prepared in-house and dissolution profiles determined using the U.S.P. XXII Dissolution Test. Distilled water was employed as the solvent. Lactose only, calcium phosphate only, a mixture of dicalcium phosphate—Avicel PH 101 and a sodium phosphate formulation consisting of lactose, L-cysteine hydrochloride and sodium phosphate were chosen as diluents. Several concentrations of the lubricant magnesium stearate were employed. The influence of 3% or 5% talc as the lubricant was studied using the sodium phosphate formulation.

The results of the study demonstrated the influence of the formulation on the dissolution of 1-131 when the concentration of magnesium stearate was held constant. This was particularly noted at a 3% concentration and to a lesser degree at a 1% concentration of magnesium stearate. The dissolution rate for 1-131 from capsules prepared with the sodium phosphate—Avicel PH 101 formulation was slow and not influenced by varying the concentration of magnesium stearate. Using talc as the lubricant resulted in 1-131 dissolution rates that were rapid for the sodium phosphate formulation. Based upon the findings it is apparent that the diluent and the lubricant can influence the dissolution rate of 1-131 from sodium iodide labeled capsules. The relationship of in vitro dissolution profiles should be compared to the bioavailability of 1-131 in animals to ascertain the importance of formulation in thyroid function studies and treatment.     

Compatibility Study Between Clenbuterol and Tablet Excipients Using Differential Scanning Calorimetry

Abstract

In order to improve the formulation of clenbuterol, the physico-chemical compatibility between this drug and various excipients commonly used in manufacturing of tablets, was studied by Differential Scanning Calorimetry (DSC).

Using this method, clenbuterol was found to be compatible with talc, stearic acid, magnesium stearate and titanium dioxide, whereas an incompatibility was shown with maize starch, pregelatinized starch, sodium starch glicollate, polyvinylpyrrolidone, avicel PH 101 and lactose.     

Compatibility Study Between Clenbuterol and Tablet Excipients Using Differential Scanning Calorimetry

In order to improve the formulation of clenbuterol, the physico-chemical compatibility between this drug and various excipients commonly used in manufacturing of tablets, was studied by Differential Scanning Calorimetry (DSC).

Using this method, clenbuterol was found to be compatible with talc, stearic acid, magnesium stearate and titanium dioxide, whereas an incompatibility was shown with maize starch, pregelatinized starch, sodium starch glicollate, polyvinylpyrrolidone, avicel PH 101 and lactose.     

Aspects of the Lubrication Requirements for an Automatic Capsule Filling Machine

Aspects of the lubrication requirements for an automatic capsule filling machine, instrumented to monitor compression and ejection forces, were studied under various filling conditions. Three common capsule fillers (compressible starch, micro-crystalline cellulose, and anhydrous lactose) were filled into No. 1 gelatin capsules. Two main sets of runs were made. The first set was designed to study the influence of powder bed height, piston height and compression force on the ejection forces generated during the filling process. The second set was aimed at comparing lubricant type and levels. It was shown that the ejection force is increased by increasing the powder bed height, piston height and compression force. Compressible starch and micro-crystalline cellulose required relatively low levels of magnesium stearate as compared to anhydrous lactose. The performance of stearic acid and especially magnesium lauryl sulfate compared favorably with magnesium stearate in compressible starch.     

Spray-Dried Rice Starch: Comparative Evaluation of Direct Compression Fillers

Spray-dried rice starch (SDRS), microcrystalline cellulose (MCC), lactose (L), pregelatinized starch (PS), and dibasic calcium phosphate (DCP) were studied for their flow behaviors and tableting properties. Both flow rate and percent compressibility values indicated that SDRS exhibited excellent flowability. The increase in magnesium stearate content reduced the hardness of MCC and SDRS tablets; however, general tablet properties were still acceptable while the PS tablets were unsatisfactory at high lubricant concentrations. The hardness of L or DCP tablets was not affected by the lubricant. The disintegration of L tablets was prolonged with the increased lubricant concentration while that of PS tablets seemed to be decreased due to softened tablets. The disintegration times of MCC and SDRS tablets seemed to be independent of the lubricant added. With respect to the dissolution, SDRS-based tablets offered fast and complete release of the drug regardless of its solubility. SDRS, L, and DCP exhibited comparable carrying capacity for ascorbic acid. The best dilution potential was obtained with MCC while the worst was obtained with PS.     

Influence of the Physicochemical Variability of Magnesium Stearate on Its Lubricant Properties: Possible Solutions

The variability of the physicochemical properties of 13 commercial batches of magnesium stearate (from three vendors) were determined using various physicochemical tests. Differences observed were related to the crystal lattice and the hydration state of the samples as well as the impurities contained in their matrices. A formulation model containing 2% of magnesium stearate was used to determine the lubricant properties of 6 of the 13 magnesium stearate lots received. The tablet press used was a Stoks® Single Station Instrumented F Press. The different lubricant properties observed were related to the particle size of the magnesium stearate lot used. The influence of the crystalline structure on the lubricant properties of magnesium stearate was also shown whereas the influence of the adsorbed water did not appear to determine process capabilities. Two possible solutions were evaluated to reduce the lubricant property differences among the lots tested. By decreasing the particle size of a lot of magnesium stearate, it has been possible to significantly improve its lubricant properties. Magnesium stearate in association with talc also presented an improvement of its lubricant properties.     

Influence of the Physicochemical Variability of Magnesium Stearate on Its Lubricant Properties: Possible Solutions

Abstract

The variability of the physicochemical properties of 13 commercial batches of magnesium stearate (from three vendors) were determined using various physicochemical tests. Differences observed were related to the crystal lattice and the hydration state of the samples as well as the impurities contained in their matrices. A formulation model containing 2% of magnesium stearate was used to determine the lubricant properties of 6 of the 13 magnesium stearate lots received. The tablet press used was a Stoks® Single Station Instrumented F Press. The different lubricant properties observed were related to the particle size of the magnesium stearate lot used. The influence of the crystalline structure on the lubricant properties of magnesium stearate was also shown whereas the influence of the adsorbed water did not appear to determine process capabilities. Two possible solutions were evaluated to reduce the lubricant property differences among the lots tested. By decreasing the particle size of a lot of magnesium stearate, it has been possible to significantly improve its lubricant properties. Magnesium stearate in association with talc also presented an improvement of its lubricant properties.     

Spray-Dried Rice Starch: Comparative Evaluation of Direct Compression Fillers

Abstract

Spray-dried rice starch (SDRS), microcrystalline cellulose (MCC), lactose (L), pregelatinized starch (PS), and dibasic calcium phosphate (DCP) were studied for their flow behaviors and tableting properties. Both flow rate and percent compressibility values indicated that SDRS exhibited excellent flowability. The increase in magnesium stearate content reduced the hardness of MCC and SDRS tablets; however, general tablet properties were still acceptable while the PS tablets were unsatisfactory at high lubricant concentrations. The hardness of L or DCP tablets was not affected by the lubricant. The disintegration of L tablets was prolonged with the increased lubricant concentration while that of PS tablets seemed to be decreased due to softened tablets. The disintegration times of MCC and SDRS tablets seemed to be independent of the lubricant added. With respect to the dissolution, SDRS-based tablets offered fast and complete release of the drug regardless of its solubility. SDRS, L, and DCP exhibited comparable carrying capacity for ascorbic acid. The best dilution potential was obtained with MCC while the worst was obtained with PS.     

An Investigation into Some Pharmaceutical Interactions by Differential Scanning Calorimetry

Differential scanning calorimetry has been used to investigate the interactions between the drugs indomethacin and chlorproparaide with some tablet excipients, and also between the excipients themselves. Chlorpropamide was found to interact with both sodium starch glycolate and magnesium stearate, indomethacin with magnesium stearate and the tablet binder polyethylene glycol 6000 with microfine cellulose.     

The Effect of Lubricants on the Properties of Chloroquine Phosphate Tablets

Abstract

The properties of tablets prepared from different size fractions of chloroquine phosphate granules using different lubricants were evaluated. Lubricants used were magnesium stearate, stearic acid and talc, tablet properties studied include weight variation, crushing strength, friability and disintegration time

The effects obtained were largely dependent on the type and concentration of lubricant. Generally, as granule size increased, tablets were found to show increased weight variation, decreased hardness and increased friability. With tablets containing talc as lubricant, disintegration time was shown to decrease with increase in granule size.

There appears to be an optimum lubricant concentration for the compression of different granule size fractions.     

The effect of formulation on radioiodide thyroid uptake in the hyperthyroid cat

This investigation was designed to compare in vitro dissolution profiles from sodium iodide capsules with radioiodide thyroid uptake in hyperthyroid cats using sodium iodide capsules prepared with a formulation exhibiting a complete release of radioiodide (I-123) in vitro and a formulation with an incomplete release of radioiodide. In vitro dissolution profiles for I-123 sodium iodide capsules with two different formulations were determined using the USP XXIII dissolution test. The two formulations studied in vitro were sodium phosphate dibasic powder with 1% magnesium stearate and calcium phosphate dibasic powder with 3% magnesium stearate. By 20 min after initiation of the dissolution test, over 95% of the I-123 was released from capsules of sodium phosphate dibasic powder. The capsules of calcium phosphate dibasic powder reached 75% at 65 min, with no further release occurring thereafter. There was a statistically significant difference in the dissolution profiles of the two formulations. The thyroid uptake of I-123 from capsules exhibiting complete release and incomplete release of radioiodide was determined in hyperthyroid cats. At 4 hr, the mean percentage thyroid uptake value for sodium phosphate dibasic powder with 1% magnesium stearate (complete release formulation) was 12.0% compared to 9.4% for calcium phosphate dibasic powder with 3% magnesium stearate (incomplete release formulation); at 24 hr, the values were 34.4% compared to 23.7%. The data suggest that the incomplete dissolution profile observed in vitro may correlate with a reduction in the bioavailability of the radioiodide in vivo. However, using the Wilcoxon signed rank test, statistically significant differences did not occur between the complete release formulation and incomplete release formulation at either 4 hr or 24 hr (p > .05). The results of the in vivo study with five hyperthyroid cats were not conclusive due to the variability in response between individual cats.     

Compatibility Study Between Atenolol and Tablet Excipients Using Differential Scanning Calorimetry

In order to improve the formulation of atenolol the physico-chemical compatibility between the drug and various excipients, commonly used in tablet manufacturing, was studied with the aid of Differential Scanning Calorimetry (DSC).

Using this method, it was found that atenolol is compatible with starch, Sta-Rx®, Primojel®, Avicel PH®, Ac-Di-Sol®, cross-linked PVP, magnesium stearate, calcium sulphate dihydrate, dicalcium phosphate and icing sugar. Interactions of atenolol with PVP, lactose and the lubricant stearic acid were found, although it cannot be conlusively stated that interaction incompatibilities will occur during storage at room temperature.     

The Effect of Formulation on Radioiodide Thyroid Uptake in the Hyperthyroid Cat

This investigation was designed to compare in vitro dissolution profiles from sodium iodide capsules with radioiodide thyroid uptake in hyperthyroid cats using sodium iodide capsules prepared with a formulation exhibiting a complete release of radioiodide (I-123) in vitro and a formulation with an incomplete release of radioiodide. In vitro dissolution profiles for I-123 sodium iodide capsules with two different formulations were determined using the USP XXIII dissolution test. The two formulations studied in vitro were sodium phosphate dibasic powder with 1% magnesium stearate and calcium phosphate dibasic powder with 3% magnesium stearate. By 20 min after initiation of the dissolution test, over 95% of the I-123 was released from capsules of sodium phosphate dibasic powder. The capsules of calcium phosphate dibasic powder reached 75% at 65 min, with no further release occurring thereafter. There was a statistically significant difference in the dissolution profiles of the two formulations. The thyroid uptake of I-123 from capsules exhibiting complete release and incomplete release of radioiodide was determined in hyperthyroid cats. At 4 hr, the mean percentage thyroid uptake value for sodium phosphate dibasic powder with 1% magnesium stearate (complete release formulation) was 12.0% compared to 9.4% for calcium phosphate dibasic powder with 3% magnesium stearate (incomplete release formulation); at 24 hr, the values were 34.4% compared to 23.7%. The data suggest that the incomplete dissolution profile observed in vitro may correlate with a reduction in the bioavailability of the radioiodide in vivo. However, using the Wilcoxon signed rank test, statistically significant differences did not occur between the complete release formulation and incomplete release formulation at either 4 hr or 24 hr (p >. 05). The results of the in vivo study with five hyperthyroid cats were not conclusive due to the variability in response between individual cats.     

Compatibility Study Between Atenolol and Tablet Excipients Using Differential Scanning Calorimetry

Abstract

In order to improve the formulation of atenolol the physico-chemical compatibility between the drug and various excipients, commonly used in tablet manufacturing, was studied with the aid of Differential Scanning Calorimetry (DSC).

Using this method, it was found that atenolol is compatible with starch, Sta-Rx®, Primojel®, Avicel PH®, Ac-Di-Sol®, cross-linked PVP, magnesium stearate, calcium sulphate dihydrate, dicalcium phosphate and icing sugar. Interactions of atenolol with PVP, lactose and the lubricant stearic acid were found, although it cannot be conlusively stated that interaction incompatibilities will occur during storage at room temperature.     

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 Effect of the Variability in the Physical and Chemical Properties of Magnesium Stearate on the Properties of Compressed Tablets

Abstract

A series of magnesium stearate samples, supplied by foreign and domestic manufacturers, were characterized by their physical and chemical properties. The results Indicated that the samples differed significantly with respect to chemical purity, particle size and surface area. The properties of magnesium stearate lots, manufactured by the same company, were very similar. Whatever variation that was seen was principally due to different suppliers.

Microcrystall1ne cellulose tablet formulations were prepared and evaluated using samples of magnesium stearate obtained from 16 sources. Differences 1n tablet quality were observed 1n regard to bulk volume of the blends, tablet tensile strength, and tablet friability. The data revealed that the smaller particle sized magnesium stearate samples (2.4–7.0 μm), with a large surface area (10.6–14.8 m2/g), had the most detrimental effects on the physical properties of mlcrocrystalHne cellulose tablets. Regression analysis and modeling was used to define quantltate, and predict the effects of magnesium stearate source variation on the physical properties of mlcrocrystalHne cellulose blends and compressed tablets.     

Adsorption and Flotation Characteristics of the Different Types of Frothers

This article investigates the adsorption of different frothers onto talc particles. The adsorption and flotation characteristisc of tallow amine acetate (TAA) + frothers (MIBC and pine oil) was studied for talc mineral. In this study, we analyzed some parameters affecting froth flotation performance and it was determined that adsorption capacity in particular, had an important role in froth flotation enrichment. The effect of pH and adsorption time on adsorption capacity was also studied. Analyses were carried out using ultraviolet spectrometry. The results showed that MIBC had the lowest frother adsorption capacity and it improved recovery during froth flotation of on the talc. It can be said that MIBC was adsorbed on the talc surface less and provided the best conditions to generate bubbles in flotation cell.     

Adhesion of Tablets in a Rotary Tablet Press II. Effects of Blending Time,Running Time,and Lubricant Concentration

Abstract

Of the three essential functions of tablet lubricants, only the true lubricant and glidant properties have been studied in detail by objective means. Only recently has instrumentation which permits the objective measurement of the antiadhesion activity in a rotary tablet press been developed. Using a rotary press instrumented to measure the adhesion of tablets to the lower punch face, this study focuses on the adhesion of tablets in two direct compression systems. At any given compression force, adhesion of microcrystalline cellulose tablets lubricated with magnesium stearate appeared to decrease with increases in blending time or intensity of blending. Over a three-hour running time, adhesion force was found to increase to peak values and then to decline with both microcrystalline cellulose and hydrous lactose lubricated with magnesium stearate. However, ejection forces decreased gradually to apparently limiting values in each case. The adhesion of tablets to the lower punch face appeared to be affected partly by the condition of the tablet - die wall interface. Studies comparing lubricated and unlubricated microcrystalline cellulose suggest two opposing effects on tablet adhesion: (1) enhancing adhesion due to an increased reaction at the lower punch resulting from reduced die wall friction; and, (2) reducing the adhesion of tablets via the “antiadherent” effect. At the lubricant levels studied, stearic acid generally appeared to be less efficient than magnesium stearate in reducing both the adhesion and ejection forces in microcrystalline cellulose blends. However, with hydrous lactose blends, the true lubricant and antiadherent activities of stearic acid appeared to be greater than those of magnesium stearate at the 1.00% level of addition.     

The Effect of the Variability in the Physical and Chemical Properties of Magnesium Stearate on the Properties of Compressed Tablets

A series of magnesium stearate samples, supplied by foreign and domestic manufacturers, were characterized by their physical and chemical properties. The results Indicated that the samples differed significantly with respect to chemical purity, particle size and surface area. The properties of magnesium stearate lots, manufactured by the same company, were very similar. Whatever variation that was seen was principally due to different suppliers.

Microcrystall1ne cellulose tablet formulations were prepared and evaluated using samples of magnesium stearate obtained from 16 sources. Differences 1n tablet quality were observed 1n regard to bulk volume of the blends, tablet tensile strength, and tablet friability. The data revealed that the smaller particle sized magnesium stearate samples (2.4-7.0 μm), with a large surface area (10.6-14.8 m2/g), had the most detrimental effects on the physical properties of mlcrocrystalHne cellulose tablets. Regression analysis and modeling was used to define quantltate, and predict the effects of magnesium stearate source variation on the physical properties of mlcrocrystalHne cellulose blends and compressed tablets.