No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Understanding the compaction behaviour of Low-substituted HPC: Macro, micro and nano-metric evaluations
Pharmaceutical Development and Technology
Abstract
The fast development in materials science has resulted in the emergence of new pharmaceutical
materials with superior physical and mechanical properties. Low-substituted hydroxypropyl cellulose
is an ether derivative of cellulose and is praised for its multi-functionality as a binder, disintegrant,
film coating agent and as a suitable material for medical dressings. Nevertheless, very little is known
about the compaction behaviour of this polymer. The aim of the current study was to evaluate the
compaction and disintegration behaviour of four grades of L-HPC namely; LH32, LH21, LH11 and
LHB1. The macrometric properties of the four powders were studied and the compaction behaviour
was evaluated using the out-of-die method. LH11 and LH22 showed poor flow properties as the
powders were dominated by fibrous particles with high aspect ratios, which reduced the powder
flow. LH32 showed a weak compressibility profile and demonstrated a large elastic region, making it
harder for this polymer to deform plastically. These findings are supported by AFM which revealed
the high roughness of LH32 powder (100.09±18.84 nm), resulting in small area of contact, but
promoting mechanical interlocking. On the contrary, LH21 and LH11 powders had smooth surfaces
which enabled larger contact area and higher adhesion forces of 21.01±11.35 nN and 9.50±5.78 nN
respectively. This promoted bond formation during compression as LH21 and LH11 powders had low
strength yield.
... The observed compressibility and compactibility are very high and uncommon for pharmaceutical powders, especially L-HPC being a plastic binder/disintegrant [12,13]. This could be attributed to the error in the estimation of the true density value of L-HPC grades by ElShaer et al. [11], which was reported to be more than 2.5 g/cm 3 [15]. Moreover, a true density value of 1.3 g/cm 3 of all L-HPC grades has also been reported in the manufacturer's technical literature (Shin-Etsu Chemicals Co, Ltd.,Tokyo, Japan) [16]. ...
... Moreover, a true density value of 1.3 g/cm 3 of all L-HPC grades has also been reported in the manufacturer's technical literature (Shin-Etsu Chemicals Co, Ltd.,Tokyo, Japan) [16]. This confirms that true density values of L-HPC grades reported by ElShaer et al. [11] (>2.5 g/cm 3 ) were too high, thus leading to overestimation of compressibility and compactibility of L-HPC grades [17,18]. Hence, a precise and accurate calculation of compressibility and compactibility of different L-HPC grades based on established mathematical models as well as powder technology rules was required. ...
... However, detailed studies of compaction and disintegration behavior of pure L-HPC and its grades are limited. Recently, ElShaer et al. [11] reported the effect of different grades of L-HPC grades on its compaction and disintegration behavior. However, the study was limited to only four grades of L-HPC (LH-11, LH-21, LH-B1, and LH-32) with LH-11, LH-21, and LH-B1 having a similar particle size of approximately 45-50 µm and similar hydroxypropyl (HPO) content of 11%. ...
As final attributes of dosage form largely depend on the properties of excipients used, understanding the effect of physicochemical properties of excipients is important. In the present study, six grades of L-HPC with varying degrees of particle size and hydroxypropyl content and the influence of the grade on compaction as well as disintegration behavior were studied. All grades of L-HPC were compressed at different compression loads to achieve different tablet porosity. Compressibility and compactibility of L-HPC grades were evaluated using a modified Heckel equation and percolation model. Further effects of particle size and hydroxypropyl content of L-HPC on tablet porosity and disintegration time were evaluated using a 32 full-factorial design. From compaction studies, it was found that compressibility of L-HPC largely depends upon the particle size with lower particle size grade showing lower compressibility. Whereas consolidation/bonding behavior of L-HPC is independent of particle size and % hydroxypropyl content. By factorial design, it was found that particle size and % hydroxypropyl content have a significant effect on the disintegration behavior of L-HPC. It was found that smaller particle sizes and higher hydroxypropyl content of L-HPC show longer disintegration time. Thus, careful consideration of excipients selection should be made to achieve desired quality attribute of the product.
... The reciprocal slope of the linear part of the Heckel plot represents the mean yield pressure, which is an index of plastic deformation. 16) Heckel analysis is also known as the in-die method ("at-pressure method") 2,[17][18][19] and out-of-die method ("zero-pressure method"). 20,21) The in-die method requires a sensor to measure the punch displacement and compression force simultaneously, and it is essential to accurately measure the height of the powder bed in the die. ...
... It has been used to classify the deformation properties of powders during the compression, using single components of API and excipients and pharmaceutical formulations. 19,31,32) However, for in-die Heckel analysis, the mean yield pressure varies with the range of compression pressures to be linearly approximated, and the mean yield pressure is affected by the weight and true density of the sample. 24) In contrast, it is obviously that P y,in is significantly lower than P y,out because of elasticity properties. ...
A quantitative evaluation method for determining the effect of tableting speed on the compression properties of pharmaceutical powders was investigated in this study. Cilostazol and ibuprofen were used as active pharmaceutical ingredients (APIs) and mixed with lactose monohydrate and microcrystalline cellulose. Viscoelasticity was examined to evaluate the raw material, and stress relaxation tests were conducted to determine the apparent viscosity and elasticity coefficients of the placebo and two APIs. Tablets were prepared using a compaction simulator and a rotary tablet press at the tableting speeds ranging from laboratory to commercial. The in-die or out-of-die strain rate sensitivity (SRS) indices were determined as a measure of the compressibility and compactibility. The results showed that the sensitivity of the out-of-die SRS was higher than that of the in-die SRS. The out-of-die SRS of ibuprofen 20% powder, which showed high elasticity and low viscosity, was 13.3–47.9%, whereas that of the placebo and cilostazol 20% (w/w) powder was <7.5%. A peripheral speed difference of more than 300 mm/s during the out-of-die SRS was sensitive enough to detect the capping tendency. Cilostazol, which has lower elasticity and higher viscosity than ibuprofen, was tested using powder mixtures with the API concentrations of 5–40%; the compressibility SRS was <5% for all API concentrations. In contrast, the compressibility SRS of ibuprofen increased from 4.8 to 81% depending on the API concentration. Using the compressibility SRS as an index, it was possible to extract the tableting speed-dependent compressibility characteristics of API from the powder mixtures containing API.
Fullsize Image
... (Herting and Kleinebudde, 2008). Low-substituted hydroxypropyl cellulose (L-HPC) is an excipient used as disintegrant and binder due to its swelling and compressibility (Alvarez-Lorenzo et al., 2000;ElShaer et al., 2018;Onuki et al., 2018). L-HPC is available in different particle sizes and substitutions. ...
... A reduction in particle size yields tablets with higher tensile strength, while increasing the hydroxypropoxy substitution results in an increase in disintegration time. (Alvarez-Lorenzo et al., 2000;ElShaer et al., 2018). Recently, L-HPC was included in a systematic study with 81 excipients in roller compaction. ...
Despite wide commercial application of hypromellose acetate succinate (HPMCAS) in spray-dried amorphous solid dispersion (ASD) drug products, little information is available in the references on downstream processing of spray-dried dispersions with HPMCAS. Poor flow and high dilution factor are a challenge in formulating spray-dried ASDs into tablets, leaving little space for other excipients facilitating binding and disintegration. Direct compression is not possible due to the poor powder flow of spray-dried ASDs. Moisture has to be avoided due to the plasticizing properties of water on the ASD, resulting in reduced stability of the amorphous state. Thus, dry granulation by roller compaction and subsequent tablet compression is the preferred downstream process. We report the investigation of downstream processing by roller compaction and tablet compression of a high load formulation with 75% of spray-dried amorphous solid dispersion (Nifedipine:HPMCAS 1:2). A head to head comparison of microcrystalline cellulose/croscarmellose (MCC/cl-NaCMC) as binder/disintegrant vs. MCC and low-substituted hydroxypropyl cellulose (L-HPC) as excipient for binding and disintegration showed improved re-workability of the formulation with MCC/L-HPC after roller compaction. Upon transfer to the rotary press, a 45% higher tensile strength of tablets is observed after dry granulation with MCC/L-HPC.
... al. and Awad et. al. for microcrystalline cellulose and kaolin, respectively (46,47). This improvement in compactibility and tabletability of the material was attributed to the enhanced ability of solid to deform plastically and increased adhesion between particles. ...
Particle engineering of excipients, at sub-particulate level using co-processing, can provide high functionality excipients. NanoCrySP technology has been recently explored as a novel approach for the generation of nanocrystalline solid dispersion of poorly soluble drugs, using spray drying process. The purpose of the present study was to generate co-processed mannitol and sorbitol (SD-CSM) using NanoCrySP technology having similar composition to commercial co-processed excipient (Compressol® SM, CP). The characterization of excipients was performed to evaluate their various physicomechanical properties. The sub-micron crystallite size of sorbitol in the matrix of mannitol was determined using the Williamson-Hall equation and Halder-Wagner equation. The reduction in crystallite size of sorbitol and mannitol, lower melting point, and lower heat of fusion of SD-CSM could be responsible for excellent compactibility, better tabletability, and comparable compressibility with respect to CP. This was confirmed by the compressibility-tabletability-compactibility (CTC) profile and Heckel plot analysis. Overall, SD-CSM generated using NanoCrySP technology improved functionalities of excipients over CP and would be useful for direct compression application.Graphical abstract
... Elastic-plastic properties of powders and pellets. Disintegration of compacts of fast-dissolving formulation Mucoadhesion properties of polymers [82] Compression Analysis Heckle Model ...
Oral modified-release multiparticulate dosage forms, which are also referred to as oral multiple-unit particulate systems, are becoming increasingly popular for oral drug delivery applications. The compaction of polymer-coated multiparticulates into tablets to produce a sustained-release dosage form is preferred over hard gelatin capsules. Moreover, multiparticulate tablets are a promising solution to chronic conditions, patients' adherence, and swallowing difficulties if incorporated into orodispersible matrices. Nonetheless, the compaction of multiparticulates often damages the functional polymer coat, which results in a rapid release of the drug substance and the subsequent loss of sustained-release properties. This review brings to the forefront key formulation variables that are likely to influence the compaction of coated multiparticulates into sustained-release tablets. It focusses on the tabletting of coated drug-loaded pellets, microparticles, and nanoparticles with a designated section on each. Furthermore, it explores the various approaches that are used to evaluate the compaction behaviour of particulate systems.
The object of the present study is to evaluate the effect of application of low-substituted hydroxypropyl cellulose (L-HPC) 11 and B1 as excipients promoting floating in gastroretentive tablets. Directly compressed tablets were formed based on experimental design. Face-centred central composite design was applied with two factors and 3 levels, where amount of sodium alginate (X1) and L-HPC (X2) were the numerical factors. Applied types of L-HPCs and their 1:1 mixture were included in a categorical factor (X3). Studied parameters were floating lag time, floating time, floating force, swelling behaviour of tablets and dissolution of paracetamol, which was used as a model active substance. Due to their physical character, L-HPCs had different water uptake and flowability. Lower flowability was observed and lower water uptake after 60 minutes at L-HPC 11 compared to L-HPC B1. Shorter floating times were detected at L-HPC 11 and L-HPC mixtures with 0.5% content of sodium alginate, whereas alginate was the only significant factor. Evaluating results of drug release and swelling studies on floating tablets revealed correlation, which can serve to help to understand the mechanism of action of L-HPCs in the field development of gastroretentive dosage forms.
Background
Mebendazole (MBZ) is an extremely insoluble and therefore poorly absorbed drug and the variable clinical results may correlate with blood concentrations. The necessity of a prolonged high dose treatment of this drug increases the risk of adverse effects.
Methods
In the present study we prepared redispersible microparticles (RDM) containing MBZ, an oral, poorly water-soluble drug, in different proportions of low-substituted hydroxypropylcellulose (L-HPC). We investigated the microparticulate structures that emerge spontaneously upon dispersion of an RDM in aqueous medium and elucidated their influence on dissolution, and also on their oral bioavailability and therapeutic efficiency using a murine model of infection with the nematode parasite Trichinella spiralis.
Results
Elevated percentages of dissolved drug were obtained with RDM at 1:2.5 and 1:5 ratios of MBZ: L-HPC. Thermal analysis showed an amorphization of MBZ in the RDM by the absence of a clear MBZ melting peak in formulations. The rapid dissolution behavior could be due to the decreased drug crystallinity, the fast dissolution time of carriers as L-HPC, together with its superior dispersibility and excellent wetting properties. RDM-1:2.5 and RDM-1:5 resulted in increased maximum plasma concentration and area(s) under the curve (AUC)0-∞ values. Likewise, after oral administration of the RDM-1:2.5 and RDM-1:5 the AUC0-∞ were 2.67- and 2.97-fold higher, respectively, compared to those of pure MBZ. Therapeutic activity, assessed on the Trichinella spiralis life cycle, showed that RDM-1:5 was the most effective in reducing the number of parasites (4.56-fold) as compared to pure MBZ, on the encysted stage.
Conclusion
The MBZ: L-HPC RDM might be an effective way of improving oral bioavailability and therapeutic activity using low doses of MBZ (5 mg/kg), which implies a low degree of toxicity for humans.
In order to investigate the effect of using different solid state forms and specific surface area (TBET) of active pharmaceutical ingredients on tabletability and dissolution performance, the mono- and dihydrated crystalline forms of chlorothiazide sodium and chlorothiazide potassium (CTZK) salts were compared to alternative anhydrous and amorphous forms, as well as to amorphous microparticles of chlorothiazide sodium and potassium which were produced by spray drying and had a large specific surface area. The tablet hardness and tensile strength, porosity and specific surface area of single-component, convex tablets prepared at different compression pressures were characterised. Results confirmed the complexity of the compressibility mechanisms. In general it may be concluded that factors such as solid-state form (crystalline vs. amorphous), type of hydration (presence of interstitial molecules of water, dehydrates) or specific surface area of the material have a direct impact on the tabletability of the powder. It was observed that, for powders of the same solid state form, those with a larger specific surface area compacted well, and better than powders of a lower surface area, even at relatively low compression pressures. Compacts prepared at lower compression pressures from high surface area porous microparticles presented the shortest times to dissolve, when compared with compacts made of equivalent materials, which had to be compressed at higher compression pressures in order to obtain satisfactory compacts. These results suggest that such processed materials may find applications as suitable solid-state forms of APIs in fast disintegrating or fast dissolving solid dosage forms.
Physical properties often required for designing the equipments for planting, harvesting and postharvesting operations of seeds. Several physical properties of three popular wheat varieties (Shiraz, Karoun and Shiroudy) were determined and compared for moisture content in 8, 12 and 18% w.b in 2007 in University of Tehran. The average length, width and thickness were 6.75, 3.26 and 2.77 mm at a moisture content of 8% w.b., respectively. studies on rewetted wheat seeds showed that the thousand-kernel weight increased from 18.38 to 22.43g. The geometric and equivalent mean diameter, surface area, sphericity and aspect ratio at a moisture content of 8% w.b were 3.93, 3.94 mm, 48.68 mm2, 0.58, 0.48, respectively. The porosity increased from 0.43 to 0.45 %. Whereas the bulk density decreased from 0.72 to 0.66kg m-3 and the true density from 1.25 to 1.19 kg m-3, with an increasing in the moisture content range of 8B18% w.b. The static and dynamic angle of repose varied from 37.28 to 47.33 and 29.89 to 36.5o. The mean of static friction coefficient of three wheat varieties increased the linearly against surfaces of three structural materials, namely, compressed plastic (0.43 - 0.53), galvanized iron (0.33 - 0.53) and plywood (0.35 - 0.41) as the moisture content increased from 8 to 18% w.b.
This article reviews the mechanisms of bacterial adhesion to biomaterial surfaces, the factors affecting the adhesion, the techniques used in estimating bacteria-material interactions and the models that have been developed in order to predict adhesion. The process of bacterial adhesion includes an initial physicochemical interaction phase and a late molecular and cellular one. It is a complicated process influenced by many factors, including the bacterial properties, the material surface characteristics, the environmental factors, such as the presence of serum proteins and the associated flow conditions. Two categories of techniques used in estimating bacteria-material interactions are described: those that utilize fluid flowing against the adhered bacteria and counting the percentage of bacteria that detach, and those that manipulate single bacteria in various configurations which lend themselves to more specific force application and provide the basis for theoretical analysis of the receptor-ligand interactions. The theories that are reviewed are the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, the thermodynamic approach and the extended DLVO theory. Over the years, significant work has been done to investigate the process of bacterial adhesion to biomaterial surfaces, however a lot of questions still remain unanswered.
Titania nanotubes (TNTs) synthesized by an anodization process were used as a basic substrate material to create different morphologies of quasi-1D (nanoribbons), 2D (nanoflakes), and 3D (nanoparticles) structures via an alkali-controlled hydrothermal route. Graphite oxide was introduced to the hydrothermal unit to fabricate graphene oxide/reduced graphene oxide-titania nanostructure hybrid materials. The presence of NaOH and graphene oxide in the hydrothermal environment had a profound effect on the surface morphology of the nanostructures. NaOH acted as both an etchant to convert TNT surfaces into low-dimensional structures and as a reducing agent to convert graphene oxide into reduced graphene oxide. Graphene oxide inhibited the etching rate to tune the surface morphologies into 1D, 2D, and 3D nanostructures. The electrochemical supercapacitance of all the nanostructures was characterized. Among the prepared samples, the nanostructured hybrid sample of reduced graphene oxide, titania nanoflakes, and TNT exhibited enhanced electrochemical performance with quite high specific capacitance. This superior electrochemical performance is attributed to the specific nanostructure, which provides short pathways for fast transport of salt ions and improved specific surface area for more adsorption sites for the formation of an electrical double layer, which leads to fast charge transfer.
The effects of moisture on the flow properties, tensile strength, Heckel plot (particle rearrangement, yield pressure), energies involved in compaction (gross, plastic, and elastic energies), and elastic recovery are reviewed.
Cellulose, in particular cotton, is the most widely used textile fiber. This preeminence is due to a happy combination of properties, such as abundance, low cost, fine cross-section, high strengh and durability, high thermal stability, good mechanical properties, ability to absorb moisture, easy dyeability, wearing comfort, etc. However, cellulosic fibers have some inherent drawbacks which can be briefly enumerated as follows: (a) poor solubility in common solvents, which makes improvements in fibers and yarns through spinning processes almost impossible; (b) poor crease resistance, which makes garments made from cellulosic fibres crumple easily during wear; (c) lack of thermoplasticity, which is a requirement for heat setting and shaping of garments; and (d) poor dimensional stability, resulting in distortion of the garments during laundering and ironing. These drawbacks, and the fact that cellulose has encountered stiff competition from synthetic fibers, have directed attention toward improving the properties of cellulose. To achieve such improvements, the physical and/or chemical structure of cellulose must be changed.
Controlling the moisture balance between exudates and their transpiration from the surface of wounded skin is important for healing. Low-substituted hydroxypropyl cellulose (L-HPC) hydrogel sheets (HGSs) possessing high water retention and water vapor transmission properties were prepared by neutralizing the highly viscous alkaline liquid of 7–10% L-HPC. Glycerol-impregnated L-HPC hydrogel sheets (L-HPC G-HGSs) were obtained by exchanging aqueous liquid in L-HPC HGSs. The physical characteristics required for wound dressings, i.e., mechanical strength, adhesive strength, and water retention properties, as well as the water vapor transmission (WVT) properties of L-HPC HGSs and L-HPC G-HGSs were evaluated. The mechanical strengths of L-HPC HGSs were enhanced with increases in the L-HPC content. The impregnation of glycerol in L-HPC HGSs yielded a significantly elasticated sheet. The adhesive strengths of L-HPC HGSs were significantly lower than those of commercial medical dressings. Water retention in L-HPC HGSs after being stored for 2 h at 37 °C was approximately 50%. The WVT rate of 7% L-HPC HGS was approximately 40 g/m2/h, which was markedly higher than that of silicone gel type medical dressings. In conclusion, L-HPC HGSs are promising dressings that maintain an adequate moisture balance by transpiring excessive wound exudates with less damage to the healing wound.
Powder flowability of microcrystalline cellulose particles having different particle shapes, whose aspect ratios ranged from 1.8 to 6.4, was measured using the vibration shear tube method. Particles lubricated with magnesium stearate were also investigated in order to evaluate the effect of surface modification on powder flowability. Particles were discharged through a narrow gap between a vibrating tube edge and a flat bottom surface, where each particle experienced high shear forces, thus, overcoming adhesion and friction forces. Vibration amplitude was increased at a constant rate during measurement and the masses of the discharged particles were measured at consistent time intervals. Flowability profiles, i.e., the relationships between the mass flow rates of the discharged particles and their vibration accelerations, were obtained from these measurements. Critical vibration accelerations and characteristic mass flow rates were then determined from flowability profiles in order to evaluate static and dynamic friction properties. The results were compared with those obtained using conventional methods. It was found that angle of repose and compressibility were related to static and dynamic friction properties. Furthermore, it was found that particle aspect ratio more significantly affects powder flowability than does lubrication with magnesium stearate.
This work aims to develop novel benznidazole (BZN) solid dispersions (SD) to improve its solubility and bioavailability properties. Low-substituted hydroxypropylcellulose (L-HPC) and sodium deoxycholate (NaDC) were evaluated as carriers. BZN solid dispersions containing different ratios of carrier were prepared by a freeze-drying process and characterized by SEM, powder X-ray diffraction (XRD), differential scanning calorimetry (DSC) and dissolution studies. The reduced BNZ crystallinity in the new formulations was confirmed by XRD, and supported by DSC. BNZ:L-HPC solid dispersion at a 1:3 ratio (w/w) (SD-1:3 L-HPC) improved the BNZ dissolution rate (85% at 5min) in comparison with BNZ raw material (23% at 5min). However, NaDC formulations showed a prolonged release (24% at 30min for SD-1:3 NaDC), due to the formation of a sustained release matrix in acidic medium. In vivo studies performed in a murine model of Chagas disease showed that the formulation achieving the highest parasitemia suppression at a low dose of 25mg/kg/day after five days of treatment was SD-1:3 L-HPC (60% of parasitemia suppression versus 33% of suppression exerted by BNZ), suggesting that BNZ:L-HPC systems enhance the bioavailability of the drug.
A new self-consistent model is developed to treat the static contact of a microparticle with a flat barrier in the presence of molecular adhesion and surface roughness. Separation between their mean datum planes is modeled considering the elastic deformation of the microparticle and surface. The contact pressure is computed from the Lennard-Jones law following the Derjaguin approximation. The elastic deflection of the mean datum plane is calculated from the effective pressure by the half-space elastic theory. Roughness is modeled by introducing a Gaussian distribution to the gap between the surfaces. An effective pressure is defined as the statistical average of the contact pressure over the roughness heights. A solution satisfying all of the above conditions gives a self-consistent method of modeling adhesion between the microparticle and the flat barrier. Using collocation methods the equations are discretized as a large system of nonlinear algebraic equations. A continuation method is used to find the multiple numerical solutions for the mean separation and the effective contact pressure. Finally, adhesive contacts of both smooth and rough surfaces are simulated in a comparative manner to elucidate the features of surface roughness in the presence of molecular adhesion. The standard deviation of the Gaussian distribution is used as a parameter to assess the effects of roughness on the pull-off force. It is shown that increasing surface roughness significantly reduces the pull-off force and decreases the tendency for the microsphere to snap-on and snap-off.
The effect of moisture content on flowability of six pharmaceutical powders (microcrystalline cellulose (MCC), hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC), polyvinylpyrrolidone (PVP), corn starch, and potato starch) was investigated. Powder flowability was measured using established static techniques and emerging dynamic avalanche behavior measurements. Static techniques did not provide enough resolution to clearly identify changes in flowability due to increasing powder moisture content. Avalanche time and its standard deviation showed that flowability of MCC, CMC, PVP, and potato starch decreased after a critical moisture content, flowability of corn starch increased and flowability did not significantly change for HPMC. The moisture decreased flowability by forming stronger interparticle liquid bridges and increased flowability by acting as a lubricant. The dynamic density of the celluloses and PVP decreased linearly with increasing moisture content as the particles swelled with water. The starches also swelled and decreased in dynamic density, but only after a moisture content corresponding to monolayer coverage of water around the particles was reached. As flowability and dynamic density change with moisture content, to ensure consistent production of high-quality tablets, the moisture content of the powders must be measured and controlled.
The structure of Low-Substituted Hydroxypropyl Cellulose (LHPC) films obtained from aqueous sodium hydroxide solution by coagulation with aqueous sulfuric acid/sodium sulfate was investigated, mainly by Wide-Angle X-ray Diffraction (WAXD) and SEM. Both edge-on and through view WAXD patterns of films dried under compression revealed that the (110) planes of the LHPC crystals were preferentially oriented parallel to the film’s top surface. The d-spacing of (110) planes of LHPC was larger than that of cellulose II by 9%, indicating that a part of the hydroxyl groups in LHPC crystals were replaced with hydroxypropyl groups. The replacement of the (110) diffraction arc in the edge view by a strong streak at low diffraction angle, and the considerable swelling anisotropy of the films in the thickness direction suggested that water molecules penetrated not only into the amorphous regions but also into the LHPC crystals, bringing about planar fracture along the (110) planes.A complicated multicellular structure containing pores of widely varying sizes was observed in SEM micrographs of the side surface of freeze-fractured LHPC film. Each cell was surrounded by thin membranes ca. 0.1–1.0 μm in thickness. The formation of this supramolecular structure and the mechanism of selective uniplanar orientation of (110) crystal planes were discussed on the basis of the WAXD patterns, SEM micrographs and fractal analysis.
Purpose. This study determined the effects of moisture on the mechanical and powder flow properties of microcrystalline cellulose.
Methods. A variety of mechanical properties were determined as a function of solid fraction at moisture levels ranging from 0 to 12.2% and included: compaction pressure required to form a compact, dynamic indentation hardness, quasi-static indentation hardness, tensile strength, best case and worst case Bonding Index, Brittle Fracture Index, Strain Index, Compressibility Index and shear cell index.
Results. Significant changes were observed as the moisture level of microcrystalline cellulose increased. The compaction pressure required to produce a compact at a solid fraction of 0.6 decreased with increasing moisture content. The permanent deformation pressure and tensile strength of compacts were observed to be relatively independent of moisture content below about 5% moisture and then decrease as the moisture content increased further. The best case Bonding Index was also observed to be independent of moisture content below 5% and then increase with increasing moisture. The Brittle Fracture Index and worst case Bonding Index, however, did not appear to be affected by changes in moisture content. Powder flow was shown to decrease with increasing moisture content.
Conclusions. These mechanical property data are consistent with the hypothesis that water acts as a plasticizer and influences the mechanical properties of microcrystalline cellulose. At moisture levels above about 5%, the material exhibits significant changes consistent with a transition from the glassy state to the rubbery state.
The ultra high modulus polyethylene (UHMPE) fiber was treated with argon plasma in order to improve the interfacial adhesion of UHMPE fiber/vinylester composites. Argon plasma treatment of the UHMPE fiber introduces micro-pittings and roughness onto the UHMPE fiber surface. These micro-pittings and surface roughness increase the interfacial adhesion of the UHMPE fiber/vinylester composites through the mechanical interlocking between the UHMPE fiber and vinylester resin. Argon plasma treatment also changes the UHMPE fiber surface into chemically more inert state in comparison with the control UHMPE fiber surface. These chemical changes decrease the efficiency of the mechanical interlocking as the inert surface makes the wetting of the UHMPE fiber by the vinylester resin difficult. In this study, the mechanical interlocking through the micro-pittings is known to play a key role in improving the interfacial adhesion of UHMPE fiber/vinylester composites by the argon plasma treatment. However, the complete wetting of the UHMPE fiber by the vinylester resin is known to be an important requirement for the effective mechanical interlocking between the UHMPE fiber and vinylester resin.
In this report, rapidly disintegrating tablets were developed using both direct compression and wet compression methods. Tablet properties, such as porosity, tensile strength, wetting time and disintegration time were evaluated, and the formation and disintegration mechanisms of the tablets were elucidated. Formulation and preparation conditions were optimized using polynomial regression or artificial neural network (ANN).
Deep understanding of the structure-property relationships of polysaccharide derivatives depends on the ability to control the position of the substituents around the monosaccharide ring and along the chain. Equally important is the ability to analyze position of substitution. Historically, both synthetic control and analysis of regiochemistry have been very difficult for cellulose derivatives, as for most other polysaccharide derivatives. With the advent of cellulose solvents that are suitable for chemical transformations, it has become possible to carry out cellulose derivatization under conditions sufficiently mild to permit increasingly complete regiochemical control, particularly with regard to the position of the substituents around the anhydroglucose ring. In addition, new techniques for forming cellulose and its derivatives from monomers, either by enzyme-catalyzed processes or chemical polymerization, permit us to address new frontiers in regiochemical control. We review these exciting developments in regiocontrolled synthesis of cellulose derivatives and their implications for in-depth structure-property studies.
This critical review is concerned with the recent advances in graft polymerisation techniques involving cellulose and its derivatives. It summarises some of the features of cellulose structure and cellulose reactivity. Also described are the various techniques for grafting synthetic polymers from the cellulosic substrate. In addition to the traditional grafting techniques, we highlight the recent developments in polymer synthesis that allow increased control over the grafting process and permit the production of functional celluloses that possess improved physical properties and chemical properties (189 references).
Coated fine granules with water-insoluble film composed primarily of ethylcellulose, containing 20% of sparfloxacin (SPFX) and various amounts of low-substituted hydroxypropylcellulose (L-HPC) (0-52%) in the cores and which masked the bitter taste of SPFX, were orally administered to fasting rats to determine the effect of L-HPC on bioavailability. The release of SPFX in water from four kinds of these coated fine granules containing 0, 25, 40 and 52% of L-HPC showed the pseudo first order kinetics, followed by the second phase, with refractive points between 0.25 and 0.5 h. The rate constant (K1) up to 0.25 h increased with an increase [corrected] of the amount of L-HPC in the core, and the rate constant (K2) in subsequent release (the second phase) was lower than K1 in each fine granule. Areas under plasma concentration-time curves (AUC) of SPFX and the peak plasma SPFX levels (Cmax) after oral administration of coated fine granules lacking L-HPC to fasting rats were suppressed to one-eighth and one-ninth, respectively, of those obtained from the core granules that rapidly released SPFX. However, AUC and Cmax from the coated fine granules increased linearly with an increase in the amount of L-HPC in the cores, and nearly equaled those from the core fine granules when the content of L-HPC was 52%. These results confirmed that the addition of L-HPC to the cores increases not only the dissolution rate but also the bioavailability of SPFX.
Tablets of acetaminophen as a model drug were prepared with low-substituted hydroxypropylcellulose (L-HPC) of various particle sizes at various loadings in the formulation. Drug release into an aqueous dissolution medium (pH 1.2) was remarkably sustained from tablets prepared with fine L-HPC (LH41) at loadings of more than 20%. Tablets prepared with less than 20% LH41 or with coarse L-HPCs (LH11, LH21, and LH31) disintegrated in the medium, resulting in rapid release of the drug. The difference in behavior could not be explained in terms of differences in tablet strength, but in swelling and water uptake abilities of the tablet's polymer. Swelling work (swelling force), water penetration speed, and water uptake of LH41 (4.4-microns average particle size) were much smaller than those of coarse L-HPCs. The formation of a continuous gel-like layer on the surface of tablets containing more than 20% LH41 was another factor to sustain the drug release rate.
The aims of this study were to assess the potential value of low-substituted hydroxypropylcelluloses (L-HPCs) as excipients of direct compression, and to investigate relationships between the chemical and physical properties of the polymers and (a) the powder rheological behavior and (b) drug release profiles from direct compressed tablets elaborated with (1:1) theophylline:L-HPC mixtures. Experiments were performed with five L-HPC varieties of different nominal particle sizes and degree of substitution. The products were characterized with regard to the moisture content, density, IR and Raman spectroscopy, hydroxypropyloxy content, heat of hydration, particle size, specific surface and porosity, and important differences were found in relation with all these properties. The differences in specific surface principally determine the flow and compaction properties of the powders, and the mechanical and microstructural properties of the tablets. The control of the hydroxypropyloxy content and the particle size of the L-HPCs allow the theophylline release profile to be regulated.
The removal of micrometer and submicrometer particles from dielectric and metal films represents a challenge in postchemical mechanical polishing cleaning. Proper modeling of the adhesive force between contaminant particles and these films is needed to develop optimal solutions to postchemical mechanical polishing cleaning. We have previously developed and experimentally validated a model to describe the adhesion between spherical particles and thin films. This simulation expands previous models to characterize the adhesive interaction between asymmetrical particles, characteristic of a polishing slurry, and various films. Our simulation accounts for the contact area between particles and substrates, as well as the morphology of the surfaces. Previous models fail to accurately describe the contact of asymmetrical particles interacting with surfaces. By properly accounting for nonideal and geometry and morphology, the simulation predicts a more accurate adhesive force than predictions based upon an ideal van der Waals model. The simulation is compared to experimental data taken for both semi-ideal particle-substrate systems (polystyrene latex spheres in contact with silicon films) and asymmetrical systems (alumina particles in contact with various films). Copyright 2001 Academic Press.
To decrease the sensation of roughness when a tablet, which is rapidly disintegrated by saliva (rapidly disintegrating tablet), is orally taken, we prepared rapidly disintegrating tablets using microcrystalline cellulose (Avicel PH-M series), a new type of pharmaceutical excipient that is spherical and has a very small particle size (particle size, 7-32 microm), instead of conventional microcrystalline cellulose (PH-102) used in the formulation of tablets containing acetaminophen or ascorbic acid as model drugs for tableting study. Tablets (200 mg) prepared using spherical microcrystalline cellulose, PH-M-06, with the smallest particle size (mean value, 7 microm) had sufficient crushing tolerance (approximately, 8 kg) and were very rapidly, disintegrated (within 15 s) when the mixing ratio of PH-M-06 to low-substituted hydroxypropylcellulose (L-HPC) was 9:1. Sensory evaluation by volunteers showed that PH-M-06 was superior to PH-102 in terms of the feeling of roughness in the mouth. Consequently, it was found that particle size is an important factor for tablet preparation using microcrystalline cellulose. It is possible to prepare drugs such as acetaminophen and ascorbic acid (concentration of approximately 50%) in the tablet form using PH-NM-06 in combination with L-HPC as a good disintegrant at a low compression force (1-6 kN). To solve the problem of poor fluidity in the preparation of these tablets, we investigated the use of spherical sugar granules (Nonpareil, NP-101 (sucrose and starch, composition ratio of 7:3), NP-103 (purified sucrose), NP-107 (purified lactose) and NP-108 (purified D-mannitol)). Rapidly disintegrating tablets can be prepared by the direct compression method when suitable excipients such as fine microcrystalline cellulose (PH-M-06) and spherical sugar granules (NP) are used.
The water mobility and diffusivity in the gel-layer of hydrating low-substituted hydroxypropyl cellulose (LH41) tablets with or without a drug were investigated by magnetic resonance imaging (MRI) and compared with those properties in the gel-layer of hydroxypropylmethyl cellulose (HPMC) and hydroxypropyl cellulose (HPC) tablets. For this purpose, a localized image-analysis method was newly developed, and the spin-spin relaxation time (T(2)) and apparent self-diffusion coefficient (ADC) of water in the gel-layer were visualized in one-dimensional maps. Those maps showed that the extent of gel-layer growth in the tablets was in the order of HPC>HPMC>LH41, and there was a water mobility gradient across the gel-layers of all three tablet formulations. The T(2) and ADC in the outer parts of the gel-layers were close to those of free water. In contrast, these values in the inner parts of the gel-layer decreased progressively; suggesting that the water mobility and diffusivity around the core interface were highly restricted. Furthermore, the correlation between the T(2) of (1)H proton in the gel-layer of the tablets and the drug release rate from the tablets was observed.
There are numerous examples where animals or plants synthesize extracellular high-performance skeletal biocomposites consisting of a matrix reinforced by fibrous biopolymers. Cellulose, the world's most abundant natural, renewable, biodegradable polymer, is a classical example of these reinforcing elements, which occur as whisker-like microfibrils that are biosynthesized and deposited in a continuous fashion. In many cases, this mode of biogenesis leads to crystalline microfibrils that are almost defect-free, with the consequence of axial physical properties approaching those of perfect crystals. This quite "primitive" polymer can be used to create high performance nanocomposites presenting outstanding properties. This reinforcing capability results from the intrinsic chemical nature of cellulose and from its hierarchical structure. Aqueous suspensions of cellulose crystallites can be prepared by acid hydrolysis of cellulose. The object of this treatment is to dissolve away regions of low lateral order so that the water-insoluble, highly crystalline residue may be converted into a stable suspension by subsequent vigorous mechanical shearing action. During the past decade, many works have been devoted to mimic biocomposites by blending cellulose whiskers from different sources with polymer matrixes.
As the most important skeletal component in plants, the polysaccharide cellulose is an almost inexhaustible polymeric raw material with fascinating structure and properties. Formed by the repeated connection of D-glucose building blocks, the highly functionalized, linear stiff-chain homopolymer is characterized by its hydrophilicity, chirality, biodegradability, broad chemical modifying capacity, and its formation of versatile semicrystalline fiber morphologies. In view of the considerable increase in interdisciplinary cellulose research and product development over the past decade worldwide, this paper assembles the current knowledge in the structure and chemistry of cellulose, and in the development of innovative cellulose esters and ethers for coatings, films, membranes, building materials, drilling techniques, pharmaceuticals, and foodstuffs. New frontiers, including environmentally friendly cellulose fiber technologies, bacterial cellulose biomaterials, and in-vitro syntheses of cellulose are highlighted together with future aims, strategies, and perspectives of cellulose research and its applications.
Direct measurements of the pull-off (adhesion) forces between pharmaceutical particles (beclomethasone dipropionate, a peptide-type material, and lactose) with irregular geometry and rough polymeric surfaces (series of polypropylene coatings, polycarbonate, and acrylonitrile-butadiene-styrene) were carried out using the atomic force microscope. These measurements showed that roughness of the interacting surfaces is the significant factor affecting experimentally measured pull-off forces. A broad distribution of pull-off force values was noted in the measurements, caused by a varying adhesive contact area for a particle located on rough substrate. The possibility of multiple points of contact between irregularly shaped pharmaceutical particles and substrate surfaces is demonstrated with nanoindentations of the particle in a fluoro-polymer film. Force-distance curves showing the "sawtooth" pattern are additional evidence that particles make contact with substrates at more than one point. Reduced adhesion of 10- to 14-microm-diameter lactose and peptide material particles to the polypropylene coatings with a roughness of 194 nm was found in this study. Similar pull-off force versus roughness relationships are also reported for the model spherical particles, silanized glass particle with a size of 10 microm and polystyrene particle with a diameter of 9 microm, in contact with polypropylene coatings of varying roughness characteristics. It was found that the model recently proposed by Rabinovich et al. (J. Colloid Interface Sci. 232, 1-16 (2000)) closely predicts the pull-off forces for glass and lactose particles. On the other hand, the adhesion of the peptide material and polystyrene particle to polypropylene is underestimated by about an order of magnitude with the theoretical model, in which the interacting substrates are treated as rigid materials. The underestimate is attributed to the deformation of the peptide material and polystyrene particles.
A single lot of MCC powder (Avicel PH102) was equilibrated at 0%, 11.35%, 21.6%, 38.2%, 52%, 57.5%, 75% and 84.3% relative humidity. Each equilibrated powder was compressed. Tablet density and tensile strength were measured as a function of pressure. Powder true density, tabletability, compressibility, compactibility and plasticity were obtained as a function of water content. The true density of MCC ranged 1.42-1.46 g/cm(3) and exhibited a maximum between approximately 3% and approximately 5% (wt%) moisture. Moisture up to approximately 3.3%, corresponding to monolayer coverage, did not induce profound change in MCC plasticity nor bonding strength despite reduced T(g). Consequently, the compaction properties were largely insensitive to moisture variation below 3.3% water. Above 3.3% water, higher moisture content corresponded to improved plasticity, due to the plasticizing effects of water above the critical water content, and consequently larger interparticulate bonding area when compressed. Effects of plasticization by water on bonding area were significant at low compaction pressures but diminish at higher pressures. At above 3.3% water, increasing moisture content also reduced bonding strength. Due to the interplay among the plasticity, compaction pressure and bonding strength, tablet tensile strength peaked in the range of 3.3-5.6% moisture.
Method for preparing low-substituted cellulose ethers
- Y Onda
- H Muto
- H Suzuki
Onda Y, Muto H, Suzuki H. 1978. Method for preparing low-substituted cellulose ethers. Publication number US4091205 A, 23.
Chemical nature of cellulose and its derivatives
- C B Purves
Purves CB. 1946. Chemical nature of cellulose and its derivatives.
New York: InterScience.