The Influence of Magnesium Stearate on time Dependent Strength Changes in Tablets

Changes in the mechanical strength of tablets with time are well documented. Sodium chloride tablets increase in strength by over 100% in the first hour after manufacture. It is shown that when mixed with magnesium stearate, this strength change does not occur. Results are also presented for lactose tablets, and possible mechanisms are discussed.     

The Effect of Magnesium Stearate Admixing in Different Types of Laboratory and Industrial Mixers on Tablet Crushing Strength

It is generally known that hydrophobic lubricants such as magnesium stearate can have a strong negative effect on the binding properties of directly compressible filler-binders. It was found that the decrease in binding forces is not only dependent on the tablet ingredients and the lubricant concentration used, but especially on the mixing time and mixing procedure. Most studies were performed, however with small laboratory scale mixers. In order to evaluate the effect of magnesium stearate admixing in different types of laboratory-scale and industrial mixers, the decrease in crushing strength was measured for a test formulation during mixing with the lubricant in different mixers. The formula used consisted of 90% a-lactose monohydrate 100 mesh, 9.5% microcrystalline cellulose and 0.5% magnesium stearate. The mixers used were two laboratory scale mixers: a 2 litre Turbula mixer and a 13 litre cubic mixer and five production scale mixers: a 45 litre drum mixer, 90 litre, 200 litre and 900 litre planetary mixers and a 1.000 litre V-shaped mixer, respectively. For the test formulation used, it was found that the effect of lubricant admixing on tablet crushing strength was strongly dependent on type, size and rotation speed of the mixer used.

When operated at the same rotation speed, the decrease in crushing strength was much faster for the large industrial mixers than for the small laboratory mixers. These differences were explained by differences in shear forces during the mixing process and the efficiency of the mixing procedure.

For the industrial mixers the decrease of the tablet crushing strength as an effect of lubricant admixing was mainly determined by the rotation speed and only to a small extent by the type and size of the apparatus. Moreover no effect of load could be observed between the mutual industrial mixers used.

For a prediction of the effect of lubricant admixing on tablet crushing strength in large mixers, efficient laboratory mixers, operating at high rotation speeds can be used. For this purpose a 2 litre Turbula mixer is a valuable tool in preformulation work.     

The Effect of Magnesium Stearate Admixing in Different Types of Laboratory and Industrial Mixers on Tablet Crushing Strength

Abstract

It is generally known that hydrophobic lubricants such as magnesium stearate can have a strong negative effect on the binding properties of directly compressible filler-binders. It was found that the decrease in binding forces is not only dependent on the tablet ingredients and the lubricant concentration used, but especially on the mixing time and mixing procedure. Most studies were performed, however with small laboratory scale mixers. In order to evaluate the effect of magnesium stearate admixing in different types of laboratory-scale and industrial mixers, the decrease in crushing strength was measured for a test formulation during mixing with the lubricant in different mixers. The formula used consisted of 90% a-lactose monohydrate 100 mesh, 9.5% microcrystalline cellulose and 0.5% magnesium stearate. The mixers used were two laboratory scale mixers: a 2 litre Turbula mixer and a 13 litre cubic mixer and five production scale mixers: a 45 litre drum mixer, 90 litre, 200 litre and 900 litre planetary mixers and a 1.000 litre V-shaped mixer, respectively. For the test formulation used, it was found that the effect of lubricant admixing on tablet crushing strength was strongly dependent on type, size and rotation speed of the mixer used.

When operated at the same rotation speed, the decrease in crushing strength was much faster for the large industrial mixers than for the small laboratory mixers. These differences were explained by differences in shear forces during the mixing process and the efficiency of the mixing procedure.

For the industrial mixers the decrease of the tablet crushing strength as an effect of lubricant admixing was mainly determined by the rotation speed and only to a small extent by the type and size of the apparatus. Moreover no effect of load could be observed between the mutual industrial mixers used.

For a prediction of the effect of lubricant admixing on tablet crushing strength in large mixers, efficient laboratory mixers, operating at high rotation speeds can be used. For this purpose a 2 litre Turbula mixer is a valuable tool in preformulation work.     

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.     

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.     

Effect of Mixing Time on the Lubricating Properties of Magnesium Stearate and the Final Characteristics of the Compressed Tablets

The effect of mixing time on hardness, disintegration time and ejection force in tablettlng of magnesium stearate and lactose granules was studied. The hardness of the tablets decreased with an increase in mixing time of the blends, as previously reported. A semilogarithmic plot of the hardness versus mixing time gave a straight line having a turning point. At the early phase of mixing the hardness was decreasing with a large first-order rate and then continued to decrease with another small first-order rate. The change in disintegration time or ejection force versus mixing time was basically the same as that in the hardness. This type of plot was applicable to the mixing magnesium stearate with not only granular but also powdered materials.     

Viscosity of Some Binary Mixtures of Arenes

The viscosity of 12 binary mixtures of benzene+toluene, +ethylbenzene, +isopropylbenzene, +tert-butylbenzene; toluene+ethylbenzene, +isopro- pylbenzene, +tert-butylbenzene; ethylbenzene+isopropylbenzene; isopropylbenzene+tert-butylbenzene; o-xylene+m-xylene; m-xylene+p-xylene; and p-xylene+o-xylene has been measured over the entire range of composition. The viscosity deviations and excess Gibbs energy of activation G ^*E of viscous flow based on Eyring's theory have been calculated. The results have been analyzed in terms of the change in the structure of pure component molecules. The viscosity data have been correlated with the equations of Grunberg and Nissan; Hind, McLaughlin, and Ubbelohde; Tamura and Kurata; Katti and Chaudhri; McAllister; and Heric and Brewer. The Prigogine–Flory–Patterson– Bloomfield–Dewan (PFPBD) theory has been applied to analyze the excess viscosity of the present binary mixtures.     

The Determination of relative amounts of Phases in Binary Mixtures with Quantitative X-Ray Diffraction

Abstract

The quantitative x-ray diffraction analysis offers often an exact and practical technique to determine the relative amounts of the phases of the solid in question. The sample may contain only one amorphous phase.

The purpose of this paper is to estimate the suitability of this technique to quantify the phase fractions of pharmaceutical substances. Three different method were used to determine the relative amounts of phases. Methods were compared and the major sources of error were estimated. The measurements and calculations are carried out using selegilin hydrochloride, mannitol and modified starch as an example. The results show that the amount of about 2 % of selegilin hydrochloride can be observed reliably from among the mannitol (crystalline substance) or modified starch (amorphous substance). During the work it became obvious that the accuracy of these calculations can essentially be improved planning the measurements carefully.     

The Determination of relative amounts of Phases in Binary Mixtures with Quantitative X-Ray Diffraction

The quantitative x-ray diffraction analysis offers often an exact and practical technique to determine the relative amounts of the phases of the solid in question. The sample may contain only one amorphous phase.

The purpose of this paper is to estimate the suitability of this technique to quantify the phase fractions of pharmaceutical substances. Three different method were used to determine the relative amounts of phases. Methods were compared and the major sources of error were estimated. The measurements and calculations are carried out using selegilin hydrochloride, mannitol and modified starch as an example. The results show that the amount of about 2 % of selegilin hydrochloride can be observed reliably from among the mannitol (crystalline substance) or modified starch (amorphous substance). During the work it became obvious that the accuracy of these calculations can essentially be improved planning the measurements carefully.     

Compaction Properties of Spheronized Binary Granular Mixtures

Two spheronized granular formulations containing 20% anhydrous lactose/80% microcrystalline cellulose (MCC) and 80% anhydrous lactose/20% microcrystalline cellulose were blended in various proportions and compressed. Physical-mechanical properties of the resulting compacts were investigated using tableting indices and compared with powder mixtures of the same compositions. The compacts were compressed at a solid fraction of 0.80 for both powder and bead mixtures. An additional set of bead compacts were made at a solid fraction of 0.87. The thickness of the compacts was measured in the post-ejection stage to investigate their expansion behavior. The tensile strength with and without a stress concentrator and the dynamic indentation hardness of the compacts were determined. The brittle fracture index (BFI) and bonding index (BI) values were also calculated. The microstructure of the beads and compacts were investigated using scanning electron microscopy to observe the bonding phenomena. The results showed that the compacts made from beads underwent different compaction/consolidation behaviors than the powders of the same lactose/MCC compositions. For powdered compacts, the tensile strength with or without a stress concentrator increased with increasing MCC content while the compacts made from beads showed the opposite trend. However, this trend was not seen in the indentation hardness test. The resulting BFI values were all low due to the plastic nature of the materials selected. The BI values of the bead and powder compacts also exhibited opposite tendencies and reflected the divergent mechanical properties of the materials presented in granulated and powdered forms. Microstructure studies revealed the bonding states between the beads in the compacts. Discrepancies in mechanical properties were related to the compressibility, compactibility, and porosities of the excipients studied.     

Quantification of Lubricant Activity of Magnesium Stearate by Atomic Force Microscopy

Magnesium stearate (MgSt) is commonly used in pharmaceutical formulations as a lubricant to facilitate tablet release from the die after compression. In this study, we quantify the effect of MgSt on the interaction forces between microcrystalline cellulose (MCC) and steel surfaces. A quantitative approach to better understand the mechanism by which MgSt affects powder performance will assist in improved control and formulation design. We find that the forces between MgSt and steel surface are stronger than the interactions between MgSt itself, between MgSt and an MCC particle, and an MCC particle and a steel surface. These quantitative findings offer an explanation how MgSt facilitates lubrication during tablet ejection.     

Influence of Magnesium Stearate on the Homogeneity of a Prednisone-Granule Ordered Mix

The use of ordered systems has been advocated in the formulation of microdose delivery systems to improve and maintain drug homogeneity during mixing. This study considered the effect of a lubricant such as magnesium stearate on the degree of homogeneity and stability of a preformed prednisone-granule ordered mix. Micronized prednisone was mixed with starch-lactose granules to produce an ordered mix of satisfactory homogeneity. Magnesium stearate in concentrations above and below the theoretical surface saturation of the granule caused negligible change in the degree of homogeneity. Sieve analysis of the mix and subsequent analysis of size fractions for prednisone allowed the prednisone distribution within the mix to be determined. Prednisone was found to be associated with the granules in all the mixes; the magnesium stearate did not compete for the surface adsorption sites and did not dislodge the drug from the granule surface, during mixing and mild demixing conditions. However, a decrease in surface adsorbed prednisone occurred in all mixes (with and without magnesium stearate) under more severe segregating conditions.

Recent research in drug homogeneity studies in microdose tablets has highlighted serious problems in dosage variation¹. Drugs are frequently micronized to improve their release from the solid dosage form. Micronization produces drug particles which are extremely cohesive and interactive. In practice, the adequate mixing of micronized powders with other excipients may be difficult to achieve since this cohesiveness produces aggregation of drug particles and interaction of the drug with the mixer surfaces. In recent years some research effort has been applied to using the interactive nature of drug particles to improve the homogeneity of mixes^2,3. Controlled adsorption of a micronized drug particle onto a carrier particle to produce an “ordered unit” has been shown to minimize segregation within the mix^4,5. Some of the factors affecting the degree of homogeneity of “ordered mixes” have been studied^6,7. However, little research has been conducted on the influence of other excipients on the homogeneity and stability of preformed ordered mixes. A cautionary note on the use of magnesium stearate in ordered mixtures indicated that the lubricant may displace salicylic acid from a sucrose carrier under conditions of segregation⁸. The purpose of this study, therefore, was to evaluate the influence of a third component such as magnesium stearate on the degree of homogeneity and stability of a preformed prednisone-starch lactose granule ordered system during a mixing process.     

粉体粒度分布分形维数与流动性及硬脂酸镁改进流动性关系

粉体的粒度分布与粉体流动特性密切相关,粉体粒度分布分形维数可以很好地表征粉体的粒度分布情况。本文中在颗粒流动性测试时引入粒度分布分形维数,通过采用利用颗粒几何特征、便于采用数字显微和图像处理计算粉体粒度分布分形维数值的数学模型,得到粉体粒度分布分形维数值,探讨颗粒流动性表征参数与粉体粒度分布分形维数值间的关系;并就流动助剂硬脂酸镁对粉体流动性能的改进与粉体粒度分布分形维数值关系进行了初步探讨。结果表明:粉体粒度分布分形维数值可以用于表征粉体流动性能,粉体粒度分形维数值可作为指导掺杂流动助剂量的参数。     

Theory of Membrane Separation of Binary Gas Mixtures

A general approach to the solution of the problem on convective mass transfer in the process of separation of binary gas mixtures in the channels of membrane units is proposed. An integral equation for the main separation parameter -- the rate of flow of a binary mixture component through a membrane -- has been obtained.     

Evaluation of Particle Size Distribution and Specific Surface Area of Magnesium Stearate

The geometric mean diameter and several other particle size distribution parameters of nine lots of magnesium stearate from Mallinckrodt Inc. and one lot from Witco Corporation were determined using a light scattering particle size analyzer. Similarly, the specific surface area of these lots was also determined using both single and multi-point B.E.T. methods. A regression analysis of the data indicated that there was a good correlation between the specific surface area and the geometric mean diameter of the various samples. Also, the volume mean diameter, the sauter mean diameter, the 10th, 50th and 90th percentile points, and the span values were consistent with the geometric mean diameter data. The results of this study indicate that the use of a light scattering particle size analyzer provides a quick, simple and reliable technique for evaluating the batch-to-batch variability in magnesium stearate.     

钢筋抗拉强度测量结果的不确定度评定

用微机控制电液伺服式万能试验机测量钢筋的抗拉强度时,为确定测量结果的分散性即测量结果的置信区间,对影响检测结果的诸多因素进行分析,确定不确定度产生的来源,并采用A类不确定度评定和B类不确定度评定的方法,对各个不确定度分量进行评定,再根据各个量的方差和协方差算得合成标准不确定度,最终用扩展不确定表示,给出钢筋抗拉强度测量的不确定度报告。     

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.     

电线电缆抗张强度检测结果的测量不确定度评定

本文分析了电线电缆绝缘材料抗张强度检测结果测量不确定度的主要来源,介绍了抗张强度测量不确定度的评定步骤和方法,给出了评定结果.     

Factor of Thermodiffusion of Binary Mixtures Containing Alcohol Vapor

Thermodiffusion separation of the binary mixtures of argon with an ethanol, n-propanol, and iso-propanol vapor and the binary mixtures of ethanol with an n-propanol and iso-propanol vapor has been measured in the temperature range 331–347 K by the two-flask method and the thermodiffusion factor has been determined. The experimental values of the thermodiffusion factor have been compared to the results of calculation according to the Chapman-Enskog theory. __________ Translated from Inzhenerno-Fizicheskii Zhurnal, Vol. 78, No. 3, pp. 82–85, May–June, 2005.