Comparison of two Varieties of Microcrystalline Cellulose as Filler-Binders II. Hydrochlorothiazide Tablets

Abstract

In tests of direct-compression hydrochlorothiazide tablets prepared with either of two varieties of microcrystalline cellulose (Avicel PH 101 and Avicel PH 102), PH 102 tablets had better mechanical properties (owing to lower compressibility of mixtures and greater Interparticle bonding), while PH 101 tablets released the active principle faster. These differences are related to observed differences In tablet micropore structure.     

Comparison of two Varieties of Microcrystalline Cellulose as Filler-Binders II. Hydrochlorothiazide Tablets

In tests of direct-compression hydrochlorothiazide tablets prepared with either of two varieties of microcrystalline cellulose (Avicel PH 101 and Avicel PH 102), PH 102 tablets had better mechanical properties (owing to lower compressibility of mixtures and greater Interparticle bonding), while PH 101 tablets released the active principle faster. These differences are related to observed differences In tablet micropore structure.     

Weight and Weight Uniformity of Hard Gelatin Capsules Filled with Microcrystalline Cellulose and Silicified Microcrystalline Cellulose

ABSTRACT

The objective of this study was to investigate the weight and weight uniformity of hard gelatin capsules filled with microcrystalline cellulose (MCC) and silicified microcrystalline cellulose (SMCC) powdered formulations. A tamping-type encapsulation apparatus was used to fill the capsules. The four formulations that were tested included MCC alone, MCC blended with fumed silica, SMCC, and high-density SMCC (SMCC-HD). The mean capsule weight and the average variation in mean capsule weight of each formulation were determined. Both SMCC products exhibited better flow than the MCC alone, with SMCC-HD being the freest flowing of the powders investigated. Capsules filled with the SMCC products had higher fill weights than those containing the MCC powders. The SMCC-containing capsules exhibited the lowest variation in weight, although these findings were not significantly different from either of the MCC-containing capsules. Significantly higher weight variations were found in capsules filled with SMCC-HD. A relationship between Carr's compressibility index and capsule weight variation was found, with more compressible materials producing more uniformly filled capsules. No relationship could be established between powder flow and capsule weight uniformity. These findings suggest that powder flow may not be a critical parameter in ensuring capsule weight uniformity when the encapsulation equipment utilizes a tamping-type filling system.     

Extrusion-Spheronization of Blends of Carbopol 934 and Microcrystalline Cellulose

We evaluated the effects of several process variables on the pharmaceutical and drug release properties of extrusion-spheronization pellets of blends of Carbopol 934 and microcrystalline cellulose (MCC) containing a high proportion of Carbopol. The model drug was theophylline. Rheological monitoring during mixing was by mixer torque rheometry. Carbopol:MCC blends wetted with a CaCl₂ solution showed different rheological behavior compared to blends with a high proportion of MCC wetted with water only. In contrast to previous suggestions, the optimal wetting point for extrusion did not coincide with the point of peak torque, but occurred just beyond this point, at much lower torque. The influence of process variables on blend properties was investigated with a three-variable factorial design (Carbopol:MCC ratio, wetting liquid proportion, CaCl₂ :Carbopol ratio), and the influence of process variables on pellet properties with a four-variable design (the variables listed plus extrusion screen hole diameter). Blend torque values were strongly influenced by CaCl₂ proportion, while mean pellet diameter was influenced by Carbopol:MCC ratio. Mean pellet diameter also differed depending on whether the pellets contained theophylline. The observed among-formulation differences in theophylline release kinetics were largely explained by differences in pellet size and theophylline hydration state. Compaction of pellets to form tablets markedly modified the drug release profile, making it biphasic.     

Extrusion-Spheronization of Blends of Carbopol 934 and Microcrystalline Cellulose

We evaluated the effects of several process variables on the pharmaceutical and drug release properties of extrusion-spheronization pellets of blends of Carbopol 934 and microcrystalline cellulose (MCC) containing a high proportion of Carbopol. The model drug was theophylline. Rheological monitoring during mixing was by mixer torque rheometry. Carbopol:MCC blends wetted with a CaCl₂ solution showed different rheological behavior compared to blends with a high proportion of MCC wetted with water only. In contrast to previous suggestions, the optimal wetting point for extrusion did not coincide with the point of peak torque, but occurred just beyond this point, at much lower torque. The influence of process variables on blend properties was investigated with a three-variable factorial design (Carbopol:MCC ratio, wetting liquid proportion, CaCl₂ :Carbopol ratio), and the influence of process variables on pellet properties with a four-variable design (the variables listed plus extrusion screen hole diameter). Blend torque values were strongly influenced by CaCl₂ proportion, while mean pellet diameter was influenced by Carbopol:MCC ratio. Mean pellet diameter also differed depending on whether the pellets contained theophylline. The observed among-formulation differences in theophylline release kinetics were largely explained by differences in pellet size and theophylline hydration state. Compaction of pellets to form tablets markedly modified the drug release profile, making it biphasic.     

羧甲基纤维素钠／TiO2纳米复合物的制备与表征

用纳米TiO2为原料,以羧甲基纤维素钠(CMC-Na)为基体,采用共混法制得CMC-Na/TiO2纳米复合物。通过傅立叶红外光谱(FT-IR)、热重分析(TG)、透射电镜(TEM)等手段对该体系进行了表征。结果表明,由于纳米TiO2粒子的引入,CMC-Na分子FT-IR的某些特征峰的波数发生明显变化;纳米TiO2在复合物中的分散性较好;复合材料的热稳定性高于纯CMC-Na薄膜;此外,复合材料的力学性能有所提高。     

Effect of Formulation Variables on Dissolution Profile of Diclofenac Sodium from Ethyl- and Hydroxypropylmethyl Cellulose Tablets

The effects of formulation variables on the release profile of diclofenac sodium from ethyl cellulose (EC) and hydroxypropylmethyl cellulose (HPMC) matrix tablets were investigated. With increase in viscosity of ethyl cellulose used in nonaqueous granulation, a decrease in drug release from the tablets was observed, while the percentage of fines articles passed through 60 mesh) in the granulation had a significant effect on the dissolution profile. Granules containing 15% fines exhibited slow release of the drug in comparison to those containing 30% fines with EC matrices. An analysis of kinetics of drug release from hydrophobic EC matrix showed Fickian diffusion regulated dissolution. Drug release from HPMC tablets followed an apparent zero-order kinetics.     

Effect of Formulation Variables on Dissolution Profile of Diclofenac Sodium from Ethyl- and Hydroxypropylmethyl Cellulose Tablets

Abstract

The effects of formulation variables on the release profile of diclofenac sodium from ethyl cellulose (EC) and hydroxypropylmethyl cellulose (HPMC) matrix tablets were investigated. With increase in viscosity of ethyl cellulose used in nonaqueous granulation, a decrease in drug release from the tablets was observed, while the percentage of fines articles passed through 60 mesh) in the granulation had a significant effect on the dissolution profile. Granules containing 15% fines exhibited slow release of the drug in comparison to those containing 30% fines with EC matrices. An analysis of kinetics of drug release from hydrophobic EC matrix showed Fickian diffusion regulated dissolution. Drug release from HPMC tablets followed an apparent zero-order kinetics.     

Relationseips Between Drug Dissolution Profile and Gelling Agent Viscosity in Tablets Prepared with Hydroxypropylmethylcellulose (HPMC) and Sodium Carboxymethylcellulose (NaCMC) Mixtures

Two varieties of HPMC, two varieties of NaCMC and various HPMC/NaCMC mixtures were characterized with the aim of providing a sound basis for the selection of appropriate mixtures to use as gelling agents in controlled-release tablets for hydrosoluble drugs. For both HPMC and NaCMC, one variety was of high and the other of low nominal viscosity. We also investigated possible relationships between the rheological properties of HPMC/NaCMC mixtures and atenolol release from tablets prepared with such mixtures. The mean molecular weights of each polymer variety were estimated on the basis of determination of their intrinsic viscosities in aqueous dispersions. Rotational viscosimetry of 2% aqueous dispersions of the polymers and polymer mixtures revealed rheological synergism in some mixtures. Drug dissolution trials were carried out in water and 0.1 N HCl. Dissolution medium, gelling agent composition and proportion of gelling agent in the tablet all affected dissolution profiles. Fitting of Korsmeyer et al.'s equation to the data for dissolution in water indicated zero-order dissolution kinetics for all formulations. For tablets prepared with the most viscous HPMC variety, %hour dissolution efficiency was closely correlated with the apparent viscosity (shear rate 0.5 s^-1) of the aqueous dispersion of the polymer mixture used as gelling agent. Assays of tablet erosion rates indicated that the erosion mechanism may contribute to the observed zero-order dissolution kinetics, but that other factors are probably also involved.     

氧化微晶纤维素交联壳聚糖复合膜的制备及性能

目的 制备氧化微晶纤维素交联壳聚糖复合膜,并探索交联改性对壳聚糖复合薄膜性能的影响。方法 首先采用高碘酸钠氧化法对微晶纤维素进行氧化处理,制备氧化微晶纤维素,再通过溶液共混流延法制备不同质量分数(0%、1%、3%、5%、7%、9%)的氧化微晶纤维素交联壳聚糖复合薄膜。通过对复合薄膜组分、形貌、力学性能、光学性能、热稳定性及阻隔性能的表征,考察不同含量的氧化微晶纤维素对壳聚糖薄膜各性能的影响。结果 氧化微晶纤维素表面的醛基能与壳聚糖中的氨基发生交联反应,氧化微晶纤维素的加入可以改善壳聚糖薄膜的拉伸强度和断裂伸长率,复合薄膜的拉伸强度和断裂伸长率最大分别达到了43.07 MPa和19.42%;随着氧化微晶纤维素含量的增大,复合薄膜的紫外屏蔽性能增强,水蒸气透过系数增高,但热稳定性未见明显变化。结论 采用氧化微晶纤维素交联改性壳聚糖可以有效改善壳聚糖薄膜的力学性能和紫外屏蔽性能,有助于进一步扩大其包装应用范围。     

Comparative compaction properties of various Microcrystalline Cellulose types and Generic Products

Abstract

The purpose of this review is to compare the tableting properties of conventional microcrystalline cellulose (MCC) with those of other common direct compression diluents and of the numerous new MCC grades and brands recently made available. After a brief discussion of the mechanisms of consolidation involved in the formation of MCC tablets, the first section deals with the basic mechanical properties of powders important for compression. Values of parameters describing ductility, brittleness, elasticity and viscoelasticity are presented and discussed in relation with the degree of polymerization, the crystallinity, the moisture content and the morphological properties of the materials.

The tableting properties of the powders during the compression process (densification behavior, work of compression) and the mechanical strength of the finished products (compactibility) are examined. Special attention is given to the effects of moisture content, lubricants and other added substances on the performances of MCC products. Comparative tablet weight variation data are provided for several MCC types from different supplies.

Finally, aging of the MCC compacts is discussed in relation to environmental conditions, before warning the user in the conclusion on the considerable variability of MCC products currently available on the market.     

Comparative compaction properties of various Microcrystalline Cellulose types and Generic Products

The purpose of this review is to compare the tableting properties of conventional microcrystalline cellulose (MCC) with those of other common direct compression diluents and of the numerous new MCC grades and brands recently made available. After a brief discussion of the mechanisms of consolidation involved in the formation of MCC tablets, the first section deals with the basic mechanical properties of powders important for compression. Values of parameters describing ductility, brittleness, elasticity and viscoelasticity are presented and discussed in relation with the degree of polymerization, the crystallinity, the moisture content and the morphological properties of the materials.

The tableting properties of the powders during the compression process (densification behavior, work of compression) and the mechanical strength of the finished products (compactibility) are examined. Special attention is given to the effects of moisture content, lubricants and other added substances on the performances of MCC products. Comparative tablet weight variation data are provided for several MCC types from different supplies.

Finally, aging of the MCC compacts is discussed in relation to environmental conditions, before warning the user in the conclusion on the considerable variability of MCC products currently available on the market.     

Relationseips Between Drug Dissolution Profile and Gelling Agent Viscosity in Tablets Prepared with Hydroxypropylmethylcellulose (HPMC) and Sodium Carboxymethylcellulose (NaCMC) Mixtures

Abstract

Two varieties of HPMC, two varieties of NaCMC and various HPMC/NaCMC mixtures were characterized with the aim of providing a sound basis for the selection of appropriate mixtures to use as gelling agents in controlled-release tablets for hydrosoluble drugs. For both HPMC and NaCMC, one variety was of high and the other of low nominal viscosity. We also investigated possible relationships between the rheological properties of HPMC/NaCMC mixtures and atenolol release from tablets prepared with such mixtures. The mean molecular weights of each polymer variety were estimated on the basis of determination of their intrinsic viscosities in aqueous dispersions. Rotational viscosimetry of 2% aqueous dispersions of the polymers and polymer mixtures revealed rheological synergism in some mixtures. Drug dissolution trials were carried out in water and 0.1 N HCl. Dissolution medium, gelling agent composition and proportion of gelling agent in the tablet all affected dissolution profiles. Fitting of Korsmeyer et al.'s equation to the data for dissolution in water indicated zero-order dissolution kinetics for all formulations. For tablets prepared with the most viscous HPMC variety, %hour dissolution efficiency was closely correlated with the apparent viscosity (shear rate 0.5 s^?1) of the aqueous dispersion of the polymer mixture used as gelling agent. Assays of tablet erosion rates indicated that the erosion mechanism may contribute to the observed zero-order dissolution kinetics, but that other factors are probably also involved.     

聚乳酸/柠檬酸三丁酯改性微晶纤维素的制备与性能

选用微晶纤维素(MCC)和短链的柠檬酸三丁酯(TC)在溶液体系中通过酯交换反应制备表面改性纤维素(TM).扫描电镜研究发现,酯交换的改性过程完全破坏了纤维素的晶体结构,减小了纤维素的分散尺寸,由50 μm减小为200～300 nm;动态力学热分析和流变性能分析表明,纤维素的表面改性改善了其在聚乳酸中的分散效果,提升了与...     

微晶纤维素表面接枝对苯二胺的制备及其荧光性能

以微晶纤维素(MCC)为原料,高碘酸钠(NaIO4)为氧化剂首先制备了双醛纤维素(DAC),进而与对苯二胺(PPDA)进行小分子接枝反应,得到对苯二胺改性的微晶纤维素。通过红外光谱、热重分析、示差扫描量热仪和荧光显微镜分别表征了MCC氧化和接枝前后样品的变化,以及产物的荧光性能。结果表明,MCC经高碘酸钠氧化,可选择性地将C2、C3键的羟基氧化成醛基;对苯二胺接枝于DAC后可形成碳氮双键,具有明显的荧光效应。     

Acoustic Characterization of a Microcrystalline Cellulose Powder During and After Its Compression

Acoustic emissions were detected, both during the roller compaction of the microcrystalline cellulose powder and from single tablets after compaction by a single-punch tablet machine, via air using a microphone with a flat frequency response up to 20 kHz. Both of the compaction units were instrumented for the measurement of applied compressive force. The microcrystalline cellulose roller compacted using compressive forces below 30 kN showed a quite normal compaction behaviour but the product compacted at this force split into two and turned to yellow by its edges. This “capping” phenomenon was indicated by an enhancement of acoustic emission in the region of about 17-23 kHz. Acoustic emissions from single tablets after compaction by a single-punch tablet machine seemed to appear as wave packets consisting in very many frequency components that may, in addition, be time-varying. However, some small peaks were found probably being characteristic of these transient sounds.     

微晶纤维素改性大豆蛋白胶黏剂的黏结性能及热压工艺的研究

应用微晶纤维素和尿素溶液对大豆分离蛋白进行改性,得到了一系列大豆蛋白胶黏剂,考察了微晶纤维素含量、尿素浓度对胶黏剂胶黏强度的影响;进一步优化了胶黏剂的热压条件。实验结果表明:微晶纤维素改性大豆蛋白胶黏剂(MSP)的胶黏强度比未改性大豆蛋白胶黏剂的大,微晶纤维素含量对改性大豆蛋白胶黏剂胶黏强度的影响存在一个最佳值;微晶纤维素和尿素共同改性大豆蛋白胶黏剂相比仅有微晶纤维素改性的大豆蛋白胶黏剂,其胶黏强度进一步提高。研究MSP热压条件发现,其最佳热压条件为:热压温度100℃;热压压力2 MPa;热压时间10 min。     

Effects of Grinding with Microcrystalline Cellulose and Cyclodextrins on the Ketoprofen Physicochemical Properties

Ground mixtures of ketoprofen (KETO) with native crystalline β-cyclodextrin, amorphous statistically substituted methyl-β-cyclodextrin, and microcrystalline cellulose were investigated for both solid phase characterization (differential scanning calorimetry (DSC) powder X-ray diffractometry, and infrared (IR) spectrometry) and dissolution properties (dispersed amount and rotating disk methods) to evaluate the role of the carrier on the performance of the final product. The effects of different grinding conditions, partial sample dehydration, and 1 year storage at room temperature were also investigated. The results pointed out the importance of the carrier nature on the efficiency of the cogrinding process. Both cyclodextrins were much more effective than was microcrystalline cellulose, even though no true inclusion complex formation occurred by mechanochemical activation. The best results were obtained from ground mixtures with methyl-β-cyclodextrin, which showed the best amorphizing and solubilizing power toward the drug and permitted an increase of approximately 100 times its intrinsic dissolution rate constant, in comparison with the approximate 10 times increase obtained from ground mixtures with β-cyclodextrin.     

Quantitation of Flurbiprofen in Tablets Using High Performance Liquid Chromatography

A stability-indicating high-performance liquid chromatography method for the quantitation of flurbiprofen in tablets was developed. The method is accurate and precise with a percent relative standard deviation of 0.7 based on 8 readings. A number of inactive ingredients present in the tablets did not interfere with the assay procedure. The extraction procedure from the tablets is very simple. The recovery from the synthetic mixtures was quantitative. The drug appears to be very sensitive to strong acids and bases since a 5 minute boiling caused the degradation of drug (100 %) in both the solutions