Effect of Active Raw Material Variability on Tablet Production: Physicochemical, Physiocomechanical and Pilot Plant Studies

Batch-to-batch variation in an active raw material was evaluated following a production process change by the raw material supplier. Physicochemical and physicomechanical tests were applied and indicated that polymorphism or solvate formation was not occurring but changes in crystal properties in terms of size and degree of aggregation were involved. Other more subtle differences in crystal properties were also possible

The deleterious effect of the raw material process change on tablet production was noted and a method of overcoming the problem identified

The necessity for comprehensive? reformulation studies including physicomechanical screening is underlined. Such studies are also necessary if changes in raw material production methods occur to avoid process problems related to the marked hatch-to-batch variation that can occur in these instances     

Project,Design, and Use of a Pilot Plant for Nanocapsule Production

The aim of this study was to find the scale-up parameters necessary for the preparation of nanocapsules (NCs) for pharmaceutical purposes. Starting from the laboratory scale (0.06 L), we designed and assembled a pilot plant (2 L) to produce NCs with the so-called emulsification-diffusion technique. We wanted to check if classical tools adequate for the pharmaceutical industry and for industrial scale-up purposes according to well-known chemical engineering technique could be used to perform the NC preparation. Experiments were carried out by varying some operative parameters, such as the impeller speed, the agitation duration for the emulsion preparation, and the reagent concentrations. As expected, good accordance between the NC produced at the laboratory scale and at the pilot plant scale was obtained. We conclude that the pilot plant can be used to perform a scale-up study of the industrial production of NC.     

Project, Design, and Use of a Pilot Plant for Nanocapsule Production

The aim of this study was to find the scale-up parameters necessary for the preparation of nanocapsules (NCs) for pharmaceutical purposes. Starting from the laboratory scale (0.06 L), we designed and assembled a pilot plant (2 L) to produce NCs with the so-called emulsification-diffusion technique. We wanted to check if classical tools adequate for the pharmaceutical industry and for industrial scale-up purposes according to well-known chemical engineering technique could be used to perform the NC preparation. Experiments were carried out by varying some operative parameters, such as the impeller speed, the agitation duration for the emulsion preparation, and the reagent concentrations. As expected, good accordance between the NC produced at the laboratory scale and at the pilot plant scale was obtained. We conclude that the pilot plant can be used to perform a scale-up study of the industrial production of NC.     

Particle Morphology of Amorphous Aluminum Hydroxycarbonate and Its Effect on Tablet Production

The particle morphology of amorphous aluminum hydroxycarbonate was studied by disaggregation induced by phosphate adsorption and direct observation by high resolution transmission electron microscopy. The primary particles are sheet-like and have equivalent diameters of 55A or less. The primary particles are believed to correspond to planar polymers comprised of six-membered rings of aluminum ions joined by double hydroxide bridges. Secondary particles form by attractive interaction of primary particles. The size of the primary particles affects the porosity of the secondary particles. The granulating and tableting properties of two spray dried amorphous aluminum hydroxycarbonates were shown to be related to the size of the primary particles and the porosity of the secondary particles.     

Particle Morphology of Amorphous Aluminum Hydroxycarbonate and Its Effect on Tablet Production

Abstract

The particle morphology of amorphous aluminum hydroxycarbonate was studied by disaggregation induced by phosphate adsorption and direct observation by high resolution transmission electron microscopy. The primary particles are sheet-like and have equivalent diameters of 55A or less. The primary particles are believed to correspond to planar polymers comprised of six-membered rings of aluminum ions joined by double hydroxide bridges. Secondary particles form by attractive interaction of primary particles. The size of the primary particles affects the porosity of the secondary particles. The granulating and tableting properties of two spray dried amorphous aluminum hydroxycarbonates were shown to be related to the size of the primary particles and the porosity of the secondary particles.     

原料配比对泡沫膏体充填材料性能的影响

以水泥、粉煤灰、煤矸石、膨润土等为原料制备了泡沫膏体充填材料,采用单因素试验研究了不同水料比条件下,原料配比对泡沫膏体充填材料流动度、凝结时间、干密度及后期抗压强度的影响规律。结果表明:流动度随水料比和煤矸石掺量的增加而增加,随发泡剂和膨润土掺量的增加而减小,但在高、低水料比条件下流动度随粉煤灰掺量的增加其变化趋势略有不同;凝结时间随水料比、粉煤灰、煤矸石及发泡剂掺量的增加而延长,而膨润土掺量则对其影响不大;干密度随水料比、粉煤灰、煤矸石及发泡剂掺量的增加而减小,随膨润土掺量的增加先减后增;后期抗压强度随煤矸石、发泡剂掺量的增加而减小,随膨润土掺量的增加先增后减,在高、低水料比条件下粉煤灰对其影响规律相反,此外高水料比有助于原料之间配合成型,对强度有益,但随原料掺量的增加其强度急剧下降。     

Studies on Sustained Release I: The Biopharmaceutical Design and Production of an Inert Matrix Type Sulfamethizole Tablet,Employing Polymethylme Thacrylate

Abstract

An inert matrix type sustained release tablet of sulfamet-hizole is attempted. Sustained release dosage form design parameter values were first calculated. Thirteen different formulations were prepared using polymethylmethacrylate as the sustaining polymer. Release and dissolution profiles were determined by the flow-through cell and the rotating bottle apparatus. Experimental results were fitted to several different kinetic equations using a computer program written for this purpose. Result of the final formulation showed that the goal was achieved.

* Presented partly in the 7. Scientific Meeting of TÜBITAK (Turkish Scientific and Technical Research Council), Ankara, Oct. 1980.     

III. Segregation of Active Constituents from Tablet Formulations During Grinding: Effects on Coated Tablet Formulations

Abstract

Grinding or milling coated tablets in preparation for their assay can cause the physical separation of an active ingredient from the coating and other tablet components. This phenomenon has been shown to partially account for the poor reproducibility between duplicate assays, and for discrepancies among assays for the same group of tablets but which were composited by different methods.

The effect of compositing methods on the assay results is shown with commercial enteric coated aspirin tablets from various manufacturers. Samples for assay were prepared by manual grinding with a glass mortar and pestle, mechanical grinding with an electric tablet grinder, direct dissolution of the tablets in a suitable solvent, and uncoating of the tablets with an organic solvent prior to their manual grinding.

Suggestions are offered to minimize the effects of segregation of an active tablet ingredient during grinding or milling on the assay results.     

III. Segregation of Active Constituents from Tablet Formulations During Grinding: Effects on Coated Tablet Formulations

Grinding or milling coated tablets in preparation for their assay can cause the physical separation of an active ingredient from the coating and other tablet components. This phenomenon has been shown to partially account for the poor reproducibility between duplicate assays, and for discrepancies among assays for the same group of tablets but which were composited by different methods.

The effect of compositing methods on the assay results is shown with commercial enteric coated aspirin tablets from various manufacturers. Samples for assay were prepared by manual grinding with a glass mortar and pestle, mechanical grinding with an electric tablet grinder, direct dissolution of the tablets in a suitable solvent, and uncoating of the tablets with an organic solvent prior to their manual grinding.

Suggestions are offered to minimize the effects of segregation of an active tablet ingredient during grinding or milling on the assay results.     

Fast-Disintegrating Sublingual Epinephrine Tablets: Effect of Tablet Dimensions on Tablet Characteristics

ABSTRACT

The purpose of this study was to evaluate the effect of changing dimensions on the hardness (H), disintegration time (DT), and wetting time (WT) of fast-disintegrating epinephrine tablets for sublingual administration as potential first aid treatment for anaphylaxis. Tablet formulations I and II, containing 0% and 10% epinephrine bitartrate, respectively, and weighing 150 mg were prepared by direct compression. Formulations were compressed at a range of forces using an 8/32″ die with concave punches (CP); a 10/32″ and an 11/32″ die with CP and flat punches (FP). Tablet weight variation, content uniformity, thickness, H, DT, and WT were measured. The 8/32″, 10/32″, and 11/32″ dies resulted in tablet thickness of ranges 0.25–0.19″, 0.17–0.1″, and 0.16–0.08″, respectively. The DT and WT using the 8/32″ die were ≤10 and ≤30 sec, respectively, at H ≤5.4 ± 0.2 kg for formulation I, and H ≤5.4 ± 0.3 kg for formulation II. The DT and WT were ≤10 and ≤30 sec, respectively, using 10/32″ die/CP, 10/32″ die/FP, 11/32″ die/CP, and 11/32″ die/FP at H ≤6.2 ± 0.6 kg, ≤6.8 ± 0.4 kg, ≤4.9 ± 0.1 kg, and ≤7.2 ± 0.3 kg, respectively, for formulation I. For formulation II, the DT and WT were ≤10 sec and ≤30 sec, respectively, when H < 4 kg. No difference in DT and WT was observed between concave and flat tablets. The 11/32″ and 10/32″ dies resulted in more ideal tablet dimensions for sublingual administration, but H must be maintained <4 kg to ensure rapid DT and WT.     

Effect of Various Factors on the Corrosion and Rusting of Tooling Material Used for Tablet Manufacturing

Various factors that cause the rusting of tablet punches and dies by a hydrochloride salt were evaluated. Tooling material rich in nickel content was found to have the best resistance to rusting by the hydrochloride salt. Other factors such as humidity, temperature and contact time with this hydrochloride salt were also found to be responsible for rusting of tooling material.

The hydrogen chloride liberated from the salt was found to be the cause of rusting of tooling. A correlation between the stability of hydrochloride salt as determined by thermogravimetric analysis and its effect on rusting of tooling material was demonstrated. Optimization of tooling composition during preformulation is recommended.     

Effect of Various Factors on the Corrosion and Rusting of Tooling Material Used for Tablet Manufacturing

Abstract

Various factors that cause the rusting of tablet punches and dies by a hydrochloride salt were evaluated. Tooling material rich in nickel content was found to have the best resistance to rusting by the hydrochloride salt. Other factors such as humidity, temperature and contact time with this hydrochloride salt were also found to be responsible for rusting of tooling material.

The hydrogen chloride liberated from the salt was found to be the cause of rusting of tooling. A correlation between the stability of hydrochloride salt as determined by thermogravimetric analysis and its effect on rusting of tooling material was demonstrated. Optimization of tooling composition during preformulation is recommended.     

一种以煤为原料造气的氢气产品生产工艺概述

介绍了用煤生产的合成氨原料气，经膜分离、变压吸附和低温吸附分离提纯技术生产工业氢、纯氢或高纯氢，并对该工艺技术进行评述。     

活性包装材料与技术探讨

活性包装可以更好的对食品起到保护作用,已成为包装界关注的焦点.本文简要介绍了活性包装的定义,活性包装的材料,包装技术及现阶段活性包装的应用和活性包装应用的发展前景.     

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.     

Instrumented Tablet Press Studies on the Effect of Some Formulation and Processing Variables on the Compaction Process

Abstract

Using an instrumented tablet press, compression force-time measurements were used to evaluate the effects of formulation and processing variables on the compaction process. The effects of tablet press speed, punch size, depth of upper punch penetration (into the die), and the setting of the overload spring mechanism were studied. The effects of tablet weight, particle size and amount of lubrication were also studied. Several direct compression materials which are believed to compact by different mechanisms were used in the study. The results indicate the sensitivity of the area under the compression force-time curve and the Area/Height ratio. Some of the changes seen in the area and A/H ratio were those which would be expected from a relatively simple model of compaction/compression. The results clearly show the usefulness of the instrumented tablet press as an analytical tool in the development of tablet formulations, the evaluation of processing requirements, and the remedy of tablet production problems.     

Instrumented Tablet Press Studies on the Effect of Some Formulation and Processing Variables on the Compaction Process

Using an instrumented tablet press, compression force-time measurements were used to evaluate the effects of formulation and processing variables on the compaction process. The effects of tablet press speed, punch size, depth of upper punch penetration (into the die), and the setting of the overload spring mechanism were studied. The effects of tablet weight, particle size and amount of lubrication were also studied. Several direct compression materials which are believed to compact by different mechanisms were used in the study. The results indicate the sensitivity of the area under the compression force-time curve and the Area/Height ratio. Some of the changes seen in the area and A/H ratio were those which would be expected from a relatively simple model of compaction/compression. The results clearly show the usefulness of the instrumented tablet press as an analytical tool in the development of tablet formulations, the evaluation of processing requirements, and the remedy of tablet production problems.     

中国钛工业发展现状及原料问题

分析了我国钛工业的现状和存在的问题,指出我国有限的钛资源难以维持目前过大的钛工业生产规模,钛产品的出口又加剧了资源短缺的问题,近年来钛铁矿、钛渣等原料价格上涨体现了供求矛盾进一步加剧的现实.同时,环境污染和国外技术壁垒也制约着我国钛工业的发展,节能降耗,实现环境友好型生产,对高能耗、高污染的钛工业可持续发展尤为重要.     

The Effect of Precipitants on MnOx-Ni/TiO2 SCR Catalysts Prepared by Titanium Slag as Raw Material

Mn-Ni/TiO₂ catalysts were prepared using a joint precipitation method with acid-dissolved titanium slag as raw material for selective catalytic reduction of nitrogen oxide. The joint precipitation method was accomplished with different precipitants, such as sodium hydroxide, carbamide, ammonia, or hydrogen peroxide. The deNOx activities of the catalysts prepared by different precipitants were investigated with SCR activity reactor within temperatures of 90–350°C. It is evident that the Mn-Ni/TiO₂ catalyst with carbamide-ammonia-hydrogen peroxide as precipitant has superior catalytic activity, which the NO conversion can reach 90% at 120°C, with a wider temperature window (120–300°C) for the NH₃-SCR reaction. H₂-TPR results showed that the reduction potential of MnOx species on Mn-Ni/TiO₂ catalysts is increased compared to that of Mn/TiO₂ catalysts. Oxygen mobility is enhanced by interaction between Ni and Mn atoms due to use of carbamide-ammonia peroxide as precipitant. XPS results suggest that the presence of MnO₂ is the major phase in nickel-doped Mn/TiO₂ catalysts. Our NH₃-TPD results illustrated that the catalysts have a lot of acid-active sites, which lead to attracting more ammonia to participate in the catalytic reaction.