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The Evaluation of Powdered Cellulose as a Pharmaceutical Excipient
Abstract
Highly functional excipients including cellulose derivatives have been developed recently, and it has been reported that the use of these materials may make tablets show excellent workability as well as disintegration. Microcrystalline cellulose and powdered cellulose, in general, are representative excipients using cellulose as the raw material. In this study, powdered cellulose in particular was examined. The workability and disintegration of powdered cellulose were measured to examine its usefulness as an excipient. A standard formulation (prepared by mixing and granulating lactose and corn starch in a ratio of 7:3) was used as the control material. As a result, the addition of powdered cellulose made it possible to obtain functionally excellent tablets. In other words, tablets containing powdered cellulose showed higher hardness and faster disintegration in comparison with the standard formulation. Based on these results, it was found that powdered cellulose is a useful and functional excipient if added to the formulation in proper quantities.
... A fully automated packaging machine YS-93SRzII (Yuyama Manufacturing Co., Ltd., Osaka, Japan) was used for one dose packaging (ODP). The lactose, SP, and various SGs were dispensed at a rate of 0.2 g/package [9], and the speed of the fully automated packaging machine was set to 40 packets/min. The adhesion of SGs during the ODP process was determined by comparing the weight before and after dispensing, and recovery rate (%) was evaluated following equation; (weight without dispensing -weight with dispensing)/weight without dispensing × 100. ...
Background:
The improvement in flowability and adhesion of starch powder (SP) is essential for using starch as an excipient for lactose intolerant patients. In this study, we attempted to evaluate the usefulness of hydroxypropylcellulose with molecular weight 80,000 (HPC-80) in the preparation of the starch granules (SG) as a substitute for excipient lactose.
Methods:
Hydroxypropylcellulose with molecular weight 30,000 (HPC-30) and HPC-80 were used as binders to prepare the SG, and defined as HPC-30-SG and HPC-80-SG, respectively. Mean particle size (D50) was measured according to the Method, Optical Microscopy of Particle Size Determination in Japanese Pharmacopoeia, Eighteenth Edition, and storage stability were evaluated by measuring of the physical properties after vortexing the granules for 180 s (physical impact). The product loss rate was calculated from the weight change of the various excipients before and after the one dose packaging (ODP).
Results:
The D50 of SP (30 µm) was smaller than that of the lactose powder (115 µm). The granulation with 0.75-3% HPC-30 and HPC-80 increased the particle size of SP, and the D50 in 1.5% HPC-30-SG (255 µm) and HPC-80-SG (220 µm) were higher than that of lactose. The excipient was removed from the heat seal of the ODP, and upon visual inspection, a large amount of starchy material was observed to be adhering to the paper in the SP. On the other hand, the low recovery rate in SP was attenuated by the granulation with HPC-30 and HPC-80. In the both HPC-30 and HPC-80, the improvement in recovery rate reached a plateau at 1.5%, and the levels of recovery rate was similar to that of lactose. The recovery rate in the 0.75-3% HPC-30-SG and 0.75% HPC-80-SG were decreased by the physical impact, however, the recovery rate and amount of 1.5% and 3% HPC-80-SG were not affected by the physical impact, and these levels were similar to that of lactose.
Conclusions:
The use of HPC-80 as a binder of SG was found to produce a higher quality granule product than conventional HPC-based SG. This finding is useful in streamlining the preparation of starch-based powdered medicine in clinical applications.
A rapidly disintegrating tablet is known to be a form that can be swallowed easily because it is disintegrated by saliva in the mouth. In this study, the roller compactor and the rotary tableting machine, production equipment generally used, were employed in the manufacture of granules and tablets. Ethenzamide, a water-insoluble drug, and ascorbic acid, a water-soluble drug, were used as model drugs, and tablets containing these drugs at a rate of 70% in the formulation were prepared.
In the case of 70% ethenzamide tablets, the addition of a superior disintegrant was needed since the disintegration time of the tablet was long. As a result of examining five disintegrants, tablets prepared with Kollidon CL disintegrated the most rapidly. The amount of water adsorbed by Kollidon CL was large, and its maximum swelling speed was marked. Therefore, it was found that Kollidon CL adsorbed water the fastest compared with the other disintegrants. On the other hand, although the subjects described a gritty texture when ethenzamide tablets disintegrated in the mouth, the texture was improved on using a combination of Kollidon CL with its superior swelling power and fine-grade Kollidon CL-M with a superior distribution.
In the case of 70% ascorbic acid tablets, the addition of a superior binder was needed since the tablet could not be formed well. As a result of examining three sorts of binders, water-soluble polymers, saccharides, and water-insoluble polymers, the disintegration time was very long in the case of water-soluble polymers, and tablets failed to form in the case of saccharides. Regarding water-insoluble polymers, the tensile strength and disintegration time were good, but subjects reported a powdery texture in the mouth. The texture was improved on using a combination of water-insoluble polymers and saccharides. The combination of PC-F and EMDEX reduced the required amount of PC-F causing the powdery texture to a 5% minimum.
In order to study the effect of surface roughness and substrate material type on the adhesion of particles, measurements were made using the pendulum impact separation method using a variety of powders and substrates. Two methods were used to attach powder particles to a substrate: the free falling method and the fluidized method. When the powders were deposited on a substrate by free falling (with negligible force), the force of adhesion to the substrate with a rough surface was less than the adhesion to the smooth surface substrate. The degree of reduction in adhesive force increased as the shape of sample powder more closely resembled a sphere. When the powders were attached to a substrate under a fluidized state, a remarkable increase in adhesive force was observed in organic powder/polyvinyl chloride (PVC) systems. This is probably due to the electrostatic force produced by the collision and/or friction of particles to the PVC sheet.
Abstract In previous studies a novel agglomerated cellulose powder was shown to own advantageous properties for direct compression. Due to the favourable particle and powder properties this material has good binding and disintegration ability in direct compression tablets. In this study the dissolution properties of direct compression tablets containing the agglomerated cellulose powder as a fillerbinder were evaluated. Especially the effect of the amount of cellulose, the porosity of tablets, the solubility of drug material and the amount and the amount and mixing method of lubricant, magnesium stearate were studied. Tablets containing different amounts of cellulose with dicalcium phosphate as a filler and 10 wt % of water soluble sodium tolmetin as a drug were compressed at a constant pressure of 150 MPa. The breaking strength of tablets increased with increasing amounts of agglomerated cellulose powder. However, the dissolution of drug accelerated up to cellulose amount of 50 wt %. This was due to the ability of the agglomerated cellulose powder to enhance the water penetration into powder compact and the loosening of tablet structure, i.e. formation of cracks. Tablets containing 20 wt % of cellulose material and 10 wt % of drug material were compressed to different porosities. Tablet porosity had no effect on dissolution of poorly water soluble tolfenamic acid. Also the dissolution of water soluble sodium tolmetin was only slightly affected by the porosity of tablets. This supports the suggested disintegrant mechanism of the agglomerated cellulose powder. The expansion of cellulose agglomerates, which have been deformed, under compression, is widely responsible for the disintegration of the tablets. An increase in the amount as well as in the mixing intensity of magncsium stearate decreased the dissolution of sodium tolmetin from tablets containing 20 wt % of agglomerated cellulose. However, the intrinsic wetting and dissolution phenomens were practically unchanged when the amount of magnesium stearate was below 2 wt %. Thus, the retardation of drug dissolution was acceptable at low lubricant concentrations. The properties of tablets containing the agglomerated cellulose were compared to those containing microcrystalline cellulose. In all cases tablets containing the agglomerated cellulose powder liberated drug clearly faster and more properly than corresponding microcrystalline cellulose tablets.
A comparison of the range of microcrystalline (MCC) and microfine (MFC) cellulose from different manufacturers has been undertaken. Tests included those associated with the powder (e.g., bulk properties, particle density, particle size range, sliding friction and swelling), those associated with tablet formation (e.g., Heckel, Kawakita and force-displacement curve evaluation) and those associated with the formed tablets (e.g., mechanical strength and disintegration). Measures of bulk properties differentiated between the MCC and MFC products. Similar grades within these types were not always equivalent and divergences were not associated with particle size range. All the products possessed similar values for sliding friction. The MCC products generally had lower values for the mean yield pressure than the MFC products, although one MCC (Heweten® 10) had an atypical higher value than other MCCs. The approach of Kawakita and Lüdde (1970/71) (Powder Technol., 4 (1970/1971) 61–68) however, appeared insensitive to differences in the compressibility of the products. Treatment of the force-displacement curves by multivariate analysis of variance suggested that all the products were distinctly different. The same statistical approach applied to the relationship between mechanical strength and tabletting pressure, however, suggested that the products could be divided into three groups. The first group contained all the MCC products except one (Heweten® 12). The second group contained one MCC product (Heweten® 12) plus three MFC products, and the third group consisted of the remaining MFC products. The tablets produced at a constant force disintegrated in different times. These differences were not associated with the swelling properties of the cellulose products. Short disintegration times were often associated with tablets with poor mechanical properties. The results clearly indicate that care must be taken in changing from one cellulose product to another in an optimized tablet formulation.
Measurements have been made of the tensile strengths of samples of microcrystalline cellulose (Avicel) containing up to 15 wt.% of added moisture. The moisture causes increases in the range of interparticle forces, to, in the surface energy of the particles E02 and a parameter α which is characteristic of each material.By combining the results with sorption/ desorption isotherms measurements of the enthalpy of desorption, it is concluded that the first 3 wt.% of moisture is strongly bound within the particles. At higher levels, it appears to form pendular bonds on their surfaces.
The overall objective of this study was to compare the rheological properties and tablet characteristics of two new varieties of celluloses (Vivacel 101 and 102), recently produced and commercialized, with the classical varieties of celluloses (Avicel and Elcema). The results showed no significant differences in the rheological properties of Vivacel and Avicel, while significant differences were found between the two celluloses and Elcema. Furthermore, there were no statistically significant differences in the disintegration times and Td values of Vivacel and Avicel. In conclusion, it was found that these new celluloses offer all the known advantages of Avicel.
On the knowledge of new powdered cellulose as inactive ingredient in direct compression
- P Szabo-Revesz
- K Pintye-Hodi
- M Miseta
- B Selmeczi