Mixture Of Microcrystalline Cellulose Research Articles

Mucosal drug delivery using cellulose derivatives as a functional polymer

In order to develop nasal powder preparations with higher bioavailability for peptide delivery, the effect of a combination of hydroxypropyl cellulose (HPC) and microcrystalline cellulose (MCC) used as base materials and microenvironment for the drugs in the preparations was examined. Significant enhanced absorption of leuprolide, calcitonin and FITC-dextran was attained by the addition of a small amount of HPC to MCC. It is suggested that MCC works as an absorption enhancer by causing a locally high concentration of drugs in the vicinity of the mucosa surface. On the other hand, HPC works to increase retention of drugs on the nasal mucosa due to its gel-forming property. In comparison to the powder mixtures of MCC and HPC in which drugs were distributed to the MCC or HPC, selective distribution of drugs to MCC is shown to be a critical factor for enhancing nasal absorption. These results showed that the microenvironment of drugs in the functional base material could critically affect the nasal absorption of drugs.

Modulation of the tabletting behaviour of microcrystalline cellulose pellets by the incorporation of polyethylene glycol

This study investigated the effect of incorporating a soft material (polyethylene glycol; PEG) into pellets of microcrystalline cellulose (MCC) on the compression behaviour and compactability of the pellets. Low and high porosity MCC pellets were formed. Pellets were also formed from a 1:1 (w/w) mixture of MCC and PEG 6000 to have a porosity equal to that of the low porosity MCC pellets. The degree of compression of the pellets and the porosity, permeability to air and tensile strength of the resulting tablets were determined. Some of the tablets were also deaggregated, and the thickness and porosity of the retrieved pellets were determined. The lowest total tablet porosity was seen with tablets made from pellets containing PEG. The intergranular porosity and the permeability of these tablets were similar to those of tablets made of the high porosity MCC pellets. However, the thickness and porosity of retrieved MCC/PEG pellets were similar to those of the low porosity MCC pellets. The degree of compression levelled off at a lower pressure for the MCC/PEG pellets than for the MCC pellets.Tablet strength values for the MCC/PEG pellets was intermediate between the MCC pellet types and not greatly affected by the applied pressure. It was concluded that the deformation propensity of the pellets was, in general terms, increased due to the presence of the soft material. However, the character of the deformation behaviour changed towards an increased tendency for local deformation during compression, i.e., the ability of adjacent pellet surfaces to conform to each other increased, without marked changes in the main dimensions and porosity of the pellets.

Importance of the Fraction of Microcrystalline Cellulose and Spheronization Speed on the Properties of Extruded Pellets Made from Binary Mixtures*

The aim of the study was to prove the importance of the binary mixture composition and spheronization speed on pellet properties. Extrudates from different binary mixtures of microcrystalline cellulose (MCC) and dicalcium phosphate dihydrate were prepared with a power-consumption-controlled extruder and spheronized at different speeds. The water content of the extrudate for the production of spherical pellets was evaluated. The pellets were characterized in terms of size, shape, porosity, mechanical properties, and disintegration. The fraction of MCC in the binary mixtures had the highest impact on the pellet properties. With an increasing fraction of MCC more water was required for successful pelletization, size and porosity of the pellets decreased, and the surface tensile stress increased. These observations were evaluated using the “sponge” and the “crystallite–gel” models for MCC. The latter led to the conception that an extrudate consists of two phases: a percolating crystallite–gel phase formed by MCC and water during extrusion and a filler phase formed by the second component of the binary mixture. This two-phase concept provides explanations for the extent of shrinking during drying and for the disintegration behavior. The spheronization speed had an influence on the size but not on porosity or surface tensile stress of the pellets. The best results were obtained at intermediate spheronization velocities of 10 and 13.4 m/sec. Fundamental properties of extrudates and pellets can be described by applying a two-phase concept of the crystallite–gel model.

Effect of density on mechanical properties of sinter-hardened materials : F.Chagnon, Y.Trudel. (Quebec Metal Powders, Ltd, Canada.)

Despite the widespread use of solid-form drug delivery within the pharmaceutical industry, tablets remain challenging to formulate because their properties depend strongly on the powder composition and details of the compaction process. Powder compaction simulations, using the finite element method (FEM) in combination with the density-dependent Drucker-Prager Cap model, can be used to aid the design process of pharmaceutical tablets. Parametrisation is typically carried out manually and requires experimental data for each powder considered. This becomes cumbersome when considering different ratios of component powders. An automated parameterisation workflow was developed and validated using experimental powder mixtures of micro-crystalline cellulose and dibasic calcium phosphate dihydrate. FEM simulations reproduced experimental compaction curves with a mean error of 2.5% of the maximum compaction pressure. Moreover, a mixing methodology was developed to estimate parameters of mixtures using only pure-component parameters as input. The experimental compaction curves of mixtures were predicted with a mean error of 4.8%.

Development of an abdominal magnetic resonance (MR) contrast agent formulation with Oral Magnetic Particles (OMP, Ferristene)

A formulation for fast dispersible granules with the magnetic resonance (MR) contrast agent, Oral Magnetic Particles (OMP), was developed. The formulation contained viscosity-increasing agents (xanthan gum and a mixture of microcrystalline cellulose and sodium carboxymethylcellulose). The granules were dispersed easily in water when stirred by hand and became a viscous OMP suspension with apparent homogeneity, but does not form granule aggregates (lump), within 10 min. The dispersibility was greatly affected by the binder type and addition of disintegrant. Hydroxypropylcellulose and low-substituted hydroxypropylcellulose were preferable. The preparation method to incorporate OMP into the granules also greatly influenced the dispersibility of the granules. A fluidized bed granulation of the base granules containing additives and subsequent coating of OMP onto the granules was eventually utilized. The formulation was able to control the viscosity of the suspension by regulating the content of viscosity-increasing agent while maintaining dispersibility. The developed formulation gave a good MR contrast image in rats and no magnetic susceptibility artifact was observed.

Effect of compression speeds on the compaction properties of a 1:1 paracetamol–microcrystalline cellulose mixture prepared by single compression and by combinations of pre-compression and main-compression

A 1:1 blend of paracetamol and microcrystalline cellulose was compacted at different compression speeds by single compression or combinations of pre- and main-compression. The tensile strengths of the tablets decreased from 0.74±0.01 to 0.44±0.05 MPa as the compression speed was increased from 78 to 390 mm/s when a single compression pressure of 80 MPa was used to compress the tablets. When combinations of pre- and main-compression of 320 and 240 MPa were used to compress the tablets, tensile strengths decreased from 3.12±0.67 MPa at a compression speed of 78 mm/s to 1.24±0.36 MPa when the compression speed was 390 mm/s. The energies of compression and the ratio of elastic to plastic energies increased with increase in compression speed. This was because the material was becoming more elastic and more energy was required for the elastic expansion leading to a reduction in the energy available for plastic deformation and bond formation which resulted in a decrease in tensile strengths. Pre-compression played a major role at high compression speeds. The tensile strengths of tablets (1.2±0.08 MPa) compressed with a pre-compression of 160 MPa followed by a main-compression of 80 MPa (compression speed of 390 mm/s) were similar to the tensile strengths of tablets (1.1±0.10 MPa) compressed using a single compression of 320 MPa at the same compression speed of 390 mm/s. Thus, combinations of lower pressures can be employed to compress the material to the same tensile strength as a high single compression.

Preparation and evaluation of a compressed tablet rapidly disintegrating in the oral cavity.

In order to make a compressed tablet which can rapidly disintegrate in the oral cavity, microcrystalline cellulose and low-substituted hydroxypropylcellulose were used as disintegrants, and ethenzamide and ascorbic acid were chosen as poorly and easily water soluble model drugs, respectively. The mixture of microcrystalline cellulose and low-substituted hydroxypropylcellulose was compressed at 100--500 kgf in the absence of an active ingredient. The properties of these tablets, such as hardness, porosity, the time required for complete wetting of a tested tablet (wetting time), water uptake and disintegration time determined by a new disintegration apparatus, were investigated to elucidate the wetting and disintegration characteristics of these tablets, When the MCC/L-HPC ratio was in the range of 8:2 to 9:1, the shortest disintegration time was observed. The disintegration of tablets containing ethenzamide or ascorbic acid was examined next. Tablet disintegration time in the oral cavity was also tested, and good correlation between the disintegration behaviors in vitro and in the oral cavity was recognized.

Extrusion/spheronization--effect of moisture content and spheronization time on pellet characteristics.

As part of a larger effort aimed at optimizing the properties of pellets produced by spheronization of extruded masses, the effect of the moisture content of wet masses on extrusion force and torque was studied. The wet masses were composed of either microcrystalline cellulose (MCC) or mixtures of MCC with lactose or dicalcium phosphate. Based on the force and torque data, a moisture content "window" was defined for consistent extrusion. Moisture exerts a lubricant effect, and a moisture level of 100-120% w/w dry solid seemed necessary for the extrusion of MCC into rod-shaped, discrete pieces. Screen force clearly depended on the moisture content but was relatively insensitive to extruder speed, especially at 80% and 100% moisture content. The physical properties of pellets as a function of spheronization time were studied by sampling the material at known intervals. The percent yield, tapped density, and a two-dimensional sphericity index of an 18/20 mesh fraction of pellets were measured. Maximum yield, tapped density, and sphericity were achieved within 60 sec in the spheronizer. With increasing residence time, the shape and density were unchanged while the yield was severely reduced. Among the formulations studied, pellets with equal amounts of lactose and MCC were superior to those of pure MCC in yield, density, and sphericity. Based on these results, an outline to optimize the endpoint of the spheronization process for formulations containing MCC is suggested.

A relationship between surface free energy and polarity data and some physical properties of spheroids

Spherical particles have been produced by extrusion and spheronisation of a wet mass of lactose, microcrystalline cellulose and indomethacin (as a model drug), and of mixtures of microcrystalline cellulose, barium sulphate and glyceryl monostearate (to test the general applicability of the surface energy predictions). The surface energies of the powders were estimated from contact angle measurements. The work of cohesion of each powder, and the work of adhesion between pairs of powders were assessed, as were spreading coefficients of the powders over each other. It was found that the spheres produced without indomethacin (lactose and microcrystalline cellulose only) required a significantly higher force to cause crushing, and were also of higher density than any of the four batches which contained different levels of indomethacin. The batches with added indomethacin had similar physical properties irrespective of indomethacin loading. Spheroids containing glyceryl monostearate and barium sulphate had much higher porosities and lower crushing strengths than the indomethacin based formulations. These differences are explained in terms of much lower works of adhesion and cohesion for barium sulphate and glyceryl monostearate than were obtained for the other materials. The differences in the properties of the spheroids have been explained in terms of interfacial phenomena, and in particular the relative works of adhesion between the solids.

Moisture-Activated dry Granulation in a high Shear Mixer

AbstractThe applicability of a 25 litre high shear mixer for moisture-activated dry granulation was examined. Microcrystalline cellulose, potato starch or a mixture of 50% m/m of each was used as moisture absorbing material. The effects of water content, wet massing time, moisture absorbing material and dry mixing time on the size distribution, and the compressibility of the granulations were investigated. Tablets were compressed on a single punch press from all the granulations and on a rotary press from a few of the granulations.It was shown that the physical properties of the tablets were primarily affected by the water content, the moisture absorbing material, and the compression force. Tablets with low mass variation, high crushing strength, low friability, and short disintegration time were achieved with both tablet presses by using a mixture of microcrystalline cellulose and potato starch as moisture absorbing material.

Effect of Crystallinity of Microcrystalline Cellulose on Granulation in High-shear Mixer.

Granulation was carried out using binary mixtures of microcrystalline cellulose (MCC) and cornstarch (CS); water was used as granulating liquid. The effect of crystallinity of MCC on granulation was examined using MCC pulverized by a jet mill (J-MCC) and a vibrational rod mill (R-MCC). Crystallinity of J-MCC was nearly equal to that of intact MCC (I-MCC), but that of R-MCC was remarkably low due to the mechanochemical effect. The growth rate of granules with R-MCC was greater than those with I-MCC and J-MCC; the latter two had a grnule having a core (MCC and CS) around which CS was layered. R-MCC provided granules in which CS and abraded MCC were homogeneously mixed. In addition, R-MCC remarkably decreased the difference in drug content among the size fractions of granules compared with I-MCC. These results suggest that the decrease in crystallinity of MCC may increase the tendency of its abrasion by shear force of impeller, because of an increase of the fragile amorphous region swollen by added water; this, in turn, results in a difference in the growth mechanism and in a greater growth rate.

Consolidation and compaction characteristics of a three-component particulate system

The consolidation and compaction characteristics of a three-component particulate system consisting of dibasic calcium phosphate dihydrate (DCP), microcrystalline cellulose (MCC) and polyethylene (PE) has been studied. The effects of compression speed on mean yield pressure, extent of particle rearrangement, crushing strength, elastic recovery and energy analysis were measured. It was found that the incorporation of up to 1% w/w of PE in a mixture composed of 25% DCP and 75% MCC did not significantly compromise tablet properties and it was possible to obtain intact compacts at a relatively low compaction force of 5.0 RN. This suggested that the 25% DCP/75% MCC mixture can suitably accommodate the incorporation of a very viscoelastic material without significantly affecting bond strength. The mean yield pressure of DCP-MCC-PE compacts surprisingly decreased with a progressive increase in concentration of PE. It is suggested that relatively greater fragmentation of DCP and more efficient filling of the pores occurs as the elastic PE absorbs more of the applied force. The crushing strength of the tablets decreased with increasing speed of compression, due probably to the elastic nature and extensive energy-absorption properties of PE reducing the overall net compaction energy available for particle-particle bonding. It was found that as the mass fraction of PE was increased, this produced a corresponding increase in the elastic recovery of the tablets, due again to the high elasticity of PE. The extent of particle rearrangement (Db) decreased with increasing concentration of PE; suggesting that adhesion between the particles correspondingly increased, most likely due to complex interactions of the three components.

Evaluation of heat-conduction microcalorimetry in pharmaceutical stability studies. IV. The influence of microcrystalline cellulose on the hydration rate of anhydrous lactose

Abstract Microcalorimetry at 25.0° C, differential scanning calorimetry (DSC) and water uptake measurements were used to monitor the influence of water vapour on a 50/50 mixture of microcrystalline cellulose (MCC) and anhydrous lactose (26% α- and 74% β-lactose), and on MCC alone, after storage at various relative humidities for different lengths of time. It was shown that MCC protects anhydrous lactose when surrounded by abundant water vapour by slowing down the rate of hydration. In a limited amount of water vapour, it was shown that MCC can redistribute its absorbed water through the vapour phase. This extends the duration of incorporation of hydrate water in anhydrous lactose over that seen when anhydrous lactose is alone. In the evaluation of the microcalorimetric technique it was shown that if a process is in progression before the first microcalorimetric measurement in a series, important information can be lost and the result may be difficult to interpret. However, together with other analytical techniques, the microcalorimetric result can give a valuable indication of how the process has proceeded.

Cation-Decationized y type zeolites as catalysts of petrochemical processes (review): Khr. Dimitrov and Tsv. Bezukhanova, Neftekhimiya 23, No. 4, 454–469, 1983

A formulation for fast dispersible granules with the magnetic resonance (MR) contrast agent, Oral Magnetic Particles (OMP), was developed. The formulation contained viscosity-increasing agents (xanthan gum and a mixture of microcrystalline cellulose and sodium carboxymethylcellulose). The granules were dispersed easily in water when stirred by hand and became a viscous OMP suspension with apparent homogeneity, but does not form granule aggregates (lump), within 10 min. The dispersibility was greatly affected by the binder type and addition of disintegrant. Hydroxypropylcellulose and low-substituted hydroxypropylcellulose were preferable. The preparation method to incorporate OMP into the granules also greatly influenced the dispersibility of the granules. A fluidized bed granulation of the base granules containing additives and subsequent coating of OMP onto the granules was eventually utilized. The formulation was able to control the viscosity of the suspension by regulating the content of viscosity-increasing agent while maintaining dispersibility. The developed formulation gave a good MR contrast image in rats and no magnetic susceptibility artifact was observed.

Directly compressed tablets of acetaminophen using several binding agents.

The effects of three binding agents, microcrystalline cellulose (MCC), hydroxypropyl cellulose (HPC) and polyvinylpolypyrrolidone (PVPP), as well as a physical mixture and a freeze-dried mixture of MCC and HPC (4 : 1), on the binding and disintegrating properties of acetaminophen (AAP) tablets prepared by direct compression were studied. Swveral physical properties of the powders and tablets were also studied. The order of binding ability of the binding agents evaluated from the cohesion was as follows : freeze-dried mixture ≒MCC≒ physical mixture>HPC>PVPP. The order of hardness of AAP tablets containing various concentrations of the binding agents was as follows : freeze-dried mixture>physical mixture>MCC>HPC>PVPP. The disintegration time of AAP tablets containing MCC was very long, while that of tables containing other binding agents was short. This is probably because crystalline regions of MCC bond strongly to each other in tablets, and this is related to the small amount of water intake and low swelling ratio of MCC. PVPP was shown to have a rather large pore volume and small cohesion, and this is presumably related to the good disintegrating properties of PVPP. The physical mixture and the freeze-dried mixture of MCC and HPC were excellent binding agents and disintegrators for tablets of drug powders with poor binding properties such as AAP.

Effects of grinding on physical and chemical properties of crystalline medicinals with microcrystalline cellulose. III. Infrared spectra of medicinals in ground mixtures.

Several drugs, such as benzoic acid, aspirin, salicylic acid, and methyl p-hydroxy benzoate, all of which had intermolecular hydrogen bondings, were ground with microcrystalline cellulose respectively. Each drug was ground with β-cyclodextrin too. The inclusion compounds of each drug with β-cyclodextrin were prepared from aqueous solution. When the drugs were ground with β-cyclodextrin, rapid disappearance of X-ray diffraction peaks and that of heat of fusion of drugs, compared with microcrystalline cellulose, were observed. About the inclusion compounds, it was concluded from X-ray diffraction, thermal analysis, and ultraviolet measurements that β-cyclodextrin formed 1 : 1 adduct with each drug and the drug molecules were preffered oriented. The conditions of the drug molecules in the ground mixtures and in the inclusion compounds were investigated using infrared spectroscopy, especially by monitoring the carbonyl stretching bands near 1700 cm-1. When the dispersion of drugs into matrices were completed, the distinct frequency shift of the carbonyl stretching bands was observed in the infrared spectra of these sample. From these results, it would be reasonable to consider that in the ground mixture of microcrystalline cellulose, the drug molecules were present monomolecularly, presumably interacting with cellulose molecules by hydrogen bondings.

The properties of tablets containing microcrystalline cellulose.

Tablets have been prepared from mixtures of microcrystalline cellulose (Avicel) and spray dried lactose. Tests on these showed that a maximum value of dissolution rate occurred as the percentage of the cellulose increased. This maximum was at 4% w/w for mixtures containing Avicel PH 101 and coincided with the point of maximum liquid penetration rate. With grade PH 105 this maximum was at 2% w/w and corresponded to the optimum balance between the opposing factors of disintegration and liquid penetration rate. Addition of up to 2% w/w magnesium stearate to the formulation containing 4% w/w PH 101 grade had little effect on pore structure, but decreased the dissolution rate by retarding water penetration. Similar concentrations of Carbowax 4000 caused no such decrease.