Compressional Behaviour of an Agglomerated Cellulose Powder

The ability of an agglomerated cellulose powder to total and plastic deformation was evaluated and compared with those of Avicel PH 101, Emcocel and an experimental depolymerized cellulose powder. The elastic recovely of compressed cellulose tablets was also measured. The effects of deformation of the material during the tableting process and recovery of tablet after maximum compression on the mechanical strength of tablets were also discussed.

The apparent net work done into tablets during compression as well as the yield pressures to total and plastic deformation, determined from the Heckel treatment, showed no great differences between the agglomerated cellulose powder and the other cellulose powders. Thus all the cellulose materials studied had rather similar ability to total, i.e. elastic and plastic, deformation and to permanent, i.e. pure plastic, deformation. The obvious fragmentation of the agglomerated cellulose powder already at low compressional pressure, however, seemed to be advantageous for the formation of strong compacts.     

Compressional Behaviour of an Agglomerated Cellulose Powder

The ability of an agglomerated cellulose powder to total and plastic deformation was evaluated and compared with those of Avicel PH 101, Emcocel and an experimental depolymerized cellulose powder. The elastic recovery of compressed cellulose tablets was also measured. The effects of deformation of the material during the tableting process and recovery of tablet after maximum compression on the mechanical strength of tablets were also discussed.

The apparent net work done into tablets during compression as well as the yield pressures to total and plastic deformation, determined from the Heckel treatment, showed no great differences between the agglomerated cellulose powder and the other cellulose powders. Thus all the cellulose materials studied had rather similar ability to total, i.e. elastic and plastic, deformation and to permanent, i.e. pure plastic, deformation. The obvious fragmentation of the agglomerated cellulose powder already at low compressional pressure, however, seemed to be advantageous for the formation of strong compacts.

Both rapid and total elastic recovery of compressed cellulose tablets showed clear differences between the cellulose materials and these differences correlated with the previously measured strength of cellulose tablets. The agglomerated cellulose powder had the smallest tendency to both kind of elastic recoveries of tablets. Obviously, due to the large interparticle contact areas, the ability of this material to establish more bonds between adjacent particles during compression was greater than those of other celluloses. The elastic recovery was greatest for depolymerized cellulose tablets indicating the poorest binding ability of the particles of this material.     

Dissolution properties of direcet compression tablets containing an agglomerated cellulose powder

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.     

Tricalcium citrate – a new brittle tableting excipient for direct compression and dry granulation with enormous hardness yield

Objectives: Tricalcium citrate (TCC) was characterized as a tableting excipient for direct compression (DC) and dry granulation (DG).

Significance: Brittle materials usually lead to tablets of inferior mechanical strength compared to plastic deforming materials. A brittle material exhibiting a high tabletability with the ability to retain that behavior during recompression would represent a valuable alternative to the commonly used microcrystalline cellulose.

Methods: Tablets of TCC and other common fillers were directly compressed for the purpose of compression analysis including Heckel analysis, speed dependency, and lubricant sensitivity. DG by roller compaction of TCC was first simulated via briquetting and experiments were subsequently repeated on a roller compactor.

Results: TCC appears as an excellent flowing powder of large agglomerates consisting of lower micron to submicron platelets. Despite the brittle deformation mechanism identified in the Heckel analysis, TCC demonstrated a very high mechanical strength up to 11?MPa in conjunction with an astonishingly low solid fraction of 0.85 at a compression pressure of 400?MPa. This was seen along with hardly any speed and lubricant sensitivity. Nevertheless, disintegration time was very short. TCC tablets suffered only a little from the re-compression: a slight loss in tensile strength of 1–2?MPa was observed for granules produced via roller compaction.

Conclusions: TCC was found to be suitable for DC as a predominantly brittle deforming filler, nevertheless demonstrating an enormous hardness yield while being independent of lubrication and tableting speed. TCC furthermore retained enough bonding capacity after DG to maintain this pronounced tabletability.     

Changes in Volume and Compression Energy upon Compression of Calcium Silicate Tablets

Abstract

The compression mechanism of calcium silicate (Florite®RE, FLR)was evaluated by determining the physicochemical properties such as compression energy, volume reduction percentage during the compression process, and elastic recovery of FLR tablets. The results obtained were compared with those of microcrystalline cellulose (MCC), anhydrous dibasic calcium phosphate (ADCP), cornstarch (CS), and lactose (LAC). FLR is found to have higher plasticity in the compression process and lower elastic recovery in a wide range of tablet hardnesses compared with the other 4 excipients. The results also indicate that a large part of compression energy was consumed for plastic deformation and fragmentation of particles. These characteristics are attributable to FLR's porous structure and are responsible for FLR tablets' high hardness, an important propen'y in tablet formulation. As a consequence, it was suggested that FLR would be a useful excipient for the formation of tablets in the pharmaceutical industry.     

Controlled Release from Glycerol Palmito-Stearate Matrices Prepared by Dry-Heat Granulation and Compression at Elevated Temperature

Abstract

Diprophylline release from glycerol palmito-stearate “precirol” matrices containing different direct compression (DC) excipients, with variable dissolving/disintegrating ability, is investigated. The matrices are formed by employing dry-heat granulation and compression at elevated temperature.

Greater drug release prolongation is achieved with the dissolving DC excipients than with the swelling ones. The release is described on the basis of two biexponential first order models and the Weibull function as well.

The effect of compression conditions (temperature and pressure) on the drug release is found to be related to the compaction behaviour of the DC excipients, i.e. plastic deformation or fragmentation.     

Use of Powdered Solutions to Improve The Dissolution Rate of Polythiazide Tablets

Abstract

Solutions of polythiazide in polyethylene glycol 400 were admixed with microcrystalline cellulose (RC-591) and silica. The resulting free-flowing powder was incorporated into tablet formulations by direct compression.

The dissolution rates of polythizizde frm these tablets were significantly more rapid than from commercially available tablets. The stability of these tablets at 40°0C and high humidity was studied. The powdered solution formulas were also compared with a polythiazide dispersion in polyethylene glycol 6000 which exhibited an equally superior dissolution profile.     

Deformation and Mechanical Characteristics of Compacted Binary Mixtures of Plastic (Microcrystalline Cellulose), Elastic (Sodium Starch Glycolate), and Brittle (Lactose Monohydrate) Pharmaceutical Excipients

This work studies the tensile strength, coherence, elastic, and plastic energy of single and bi-component compacted tablets consisting of (i) microcrystalline cellulose (MCC) PH 102 as a plastic material, (ii) (SSG) as an elastic material, and (iii) alpha lactose monohydrate as a brittle material by direct compression. Compacted tablets were studied with various mass ratios formed at an ultimate compaction stress of 150 MPa. The loading and unloading stages of the compaction process for the single and binary tablets were evaluated based on the energies derived from the force-displacement data obtained. The resulting tablet quality was measured in terms of the tensile strength. Material that exhibit predominantly plastic deformation (MCC) shows a dominant property over elastically deforming sodium starch glycolate (SSG) and brittle (lactose) materials during the loading and unloading stages of the compaction process. In conclusion, the tensile strength of the formed tablets depends directly on the plastic energy and indirectly on the elastic energy and is negatively affected by the presence of a brittle material.     

Development of Agglomerated Talc. III. Comparisons of the Physical Properties of the Agglomerated Talc Prepared by Three Different Processing Methods

Abstract

Agglomerated talc was prepared by the wet granulation method using a fluidized-bed granulator, a planetary mixer, and a high-speed, high-shear mixer. It was found that agglomerated talc produced by a fluidized-bed granulator is more porous, has a more irregular shape, has a lower bulk density, and has more binder-talc contacts. This higher surface area of binder-talc interface and the highly porous and irregular shape of the agglomerated talc produced by the fluidized- bed granulator result in stronger intergranular bonding. The resultant compact was harder. The compression force-time curve also showed that the time required to increase the upper punch force from 10% to 90% was greater for the compaction of the fluidized-bed granulated talc. The longer exposure to shear forces would enhance plastic flow and facilitate the formation of stronger bonds. Phenylpropanolamine HCl tablets containing 77.5 % agglomerated talc as the diluent were prepared. The properties of the tablet were found to be satisfactory. The agglomerated talc developed may be a promising direct compression diluent.     

The changes in the Mechanic Properties of a direct tableting agent Microcrystalline Cellulose by Precompression

Abstract

In the manufacturing of tablets, direct tableting agents are not only used in direct compression, but are also used in wet granulation and slugging methods. These agents are effective only if their particle size and form is appropriate. However, the precompression, milling and grinding which are applied in the slugging method changes the particular properties of these agents.

In this study, microcrystalline cellulose tablets were prepared both by direct compression and slugging. The consolidation, compressibility and flow properties of the two mixed powders were compared. Finally, it was observed that the compressibility of the mixed powder was influenced negatively by the slugging method.     

Effect of Some Excipjents and Compression Pressure on the Adhesion of Aqueous-Based Hydroxypropyl Methylcellulose Film Coatings to Tablet Surface

Abstract

The adhesion between aqueous-based hydroxypropyl methylcellulose (HPMC) films and tablet surface was evaluated using a Lloyd LRX materials testing machine. Special attention was paid to the effects of compression pressure and the excipients (microcrystalline cellulose, lactose and a commercial combination of lactose and cellulose (Cellactose^R)) on the adhesion properties of the film.

The adhesion of HPMC films was the lowest for the tablets containing lactose as a diluent and the highest for the tablets containing microcrystalline cellulose. The adhesion to Cellactose^R-based tablets increased with increasing compression pressure. With microcrystalline cellulose (MCC) and lactose, the effect of compression pressure on film adhesion was not so clear. The increase in concentration of a hydrophopic lubricant, magnesium stearate, decreased the adhesion between the films and tablets cores. The greatest decrease was observed with the MCC tablets.

Furthermore the results showed that, the film coating increased clearly the mechanical strength of the tablets, depending on the excipient, the compression pressure and amount of magnesium stearate.     

Modeling of quantitative relationships between physicochemical properties of active pharmaceutical ingredients and tensile strength of tablets using a boosted tree

Objectives: The aim of this study was to explore the potential of boosted tree (BT) to develop a correlation model between active pharmaceutical ingredient (API) characteristics and a tensile strength (TS) of tablets as critical quality attributes.

Methods: First, we evaluated 81 kinds of API characteristics, such as particle size distribution, bulk density, tapped density, Hausner ratio, moisture content, elastic recovery, molecular weight, and partition coefficient. Next, we prepared tablets containing 50% API, 49% microcrystalline cellulose, and 1% magnesium stearate using direct compression at 6, 8, and 10?kN, and measured TS. Then, we applied BT to our dataset to develop a correlation model. Finally, the constructed BT model was validated using k-fold cross-validation.

Results: Results showed that the BT model achieved high-performance statistics, whereas multiple regression analysis resulted in poor estimations. Sensitivity analysis of the BT model revealed that diameter of powder particles at the 10th percentile of the cumulative percentage size distribution was the most crucial factor for TS. In addition, the influences of moisture content, partition coefficients, and modal diameter were appreciably meaningful factors.

Conclusions: This study demonstrates that BT model could provide comprehensive understanding of the latent structure underlying APIs and TS of tablets.     

Optimization of piribedil mucoadhesive tablets for efficient therapy of Parkinson’s disease: physical characterization and ex vivo drug permeation through buccal mucosa

Objective: The aim of this study was optimization of buccal piribedil (PR) mucoadhesive tablets to improve its low bioavailability and provide controlled release for the treatment of Parkinson’s disease.

Methods: Buccal tablets were prepared by direct compression method using carbomer (CP), carboxymethyl cellulose (CMC), and hydroxypropyl methylcellulose (HPMC) as mucoadhesive polymers. Physical properties of powder mixtures and buccal tablets were evaluated. Physicochemical compatibility between ingredients was investigated with infrared spectroscopy and differential scanning calorimetry analysis. In vitro dissolution profiles and drug release kinetics of buccal tablets were investigated. Mucoadhesion and ex vivo permeation studies were performed using sheep buccal mucosa.

Results: Powder mixtures demonstrated sufficient flow properties and physical characteristics of all tablet formulations were within compendia limits. Tablet ingredients were absent of any chemical interactions. CP tablets displayed slower drug release compared to HPMC tablets with zero order release, while CMC tablets lost their integrity and released entire drug after 6?h following Higuchi model. All formulations displayed adequate mucoadhesion and steady state flux of PR through buccal mucosa were higher with HPMC compared to CP-containing tablets.

Conclusion: Overall, HPMC was found to combine desired controlled release and mucoadhesion characteristics with sufficient pharmaceutical quality for optimization of buccal tablets. Piribedil mucoadhesive buccal tablets designed for the first time may introduce a new alternative for the treatment of Parkinson’s disease.     

Preparation and In-Vitro Evaluation of Powder Solution Tablets of Valproic Acid

Abstract

A tablet dosage form of liquid valproic acid (VPA) was formulated using powder solution technology as an alternative to the manufacturing of soft elastic gelatin capsules (SEGs). Mixing of liquid VPA with suitable adsorbents followed by blending with other excipients resulted in a non-adherent, free flowing powder. Tableting was achieved through standard direct compression. The tablets were acceptable in terms of physical properties. Film coated tablets (FCTs) and sugar coated tablets (SCTs) were also prepared. The in-vitro dissolution rates of these VPA tablets were significantly greater than that of a marketed SEG product. There was no significant change in the dissolution rates of the plain and FCTs after storage under accelerated stability conditions. Powder solution technology was a viable alternative to the commercial preparation of SEGs.     

Effect of compression force, compression speed, and particle size on the compression properties of paracetamol.

The compression characteristics of two particle size fractions (< 90 microm, 105-210 microm) of paracetamol were examined. Each fraction produced extremely weak tablets and displayed a high tendency to cap. Low correlation coefficients of the initial parts of the Heckel plots, a low strain rate sensitivity, and an increase in mean yield pressure (from 34.2 to 45.5 MPa) with decrease in particle size all confirmed that the main mechanism during the compaction of paracetamol was fragmentation. The 105-210-microm particles underwent more fragmentation than the less than 90-microm powder. Heckel analysis confirmed that the larger size fraction of paracetamol produced denser compacts than the smaller fraction. The 105-210-microm fraction resulted in tablets with lower elastic recoveries and elastic energies. The elastic, plastic energy ratios indicated that the majority of energy involved during the compaction of paracetamol was utilized as elastic energy, indicative of massive elastic deformation of paracetamol particles under pressure.     

Evaluation of Anhydrous α-Lactose,A New Excipient in Direct Compression

Abstract

Different forms of lactose are available for direct compression of tablets. The use of spray-dried lactose, which has good flow and compressibility characteristics, is limited by its stability when stored under humid conditions. Sieved crystalline fractions of α-lactose monohydrate such as the 100 mesh fraction, have very good flow properties and an outstanding stability, but the compressibility is so poor, that it can be used only in combination with other filler-binders, like microcrystalline cellulose. A third form of lactose, increasingly used in direct compression is anhydrous lactose. The commercially available products generally consist of an excess of β next to α-lactose. They both have good binding and stability characteristics, but a flowability which is less than optimum. The latter is caused by the rather irregular particle shape and the relatively high amount of fines. A newly developed form of lactose is anhydrous α-lactose. It is prepared by dehydration of α-lactose monohydrate. Binding, flow and stability properties of this excipient were compared with the properties of other filler/binders. The results show that the compressibility of anhydrous α-lactose was about the same as that of anhydrous β-lactose.

The flow properties of anhydrous α-lactose were even better than the very good fluidity of α-lactose monohydrate 100 mesh. At storage under normal or humid conditions, there was no change in hardness of tablets compressed from anhydrous α-lactose.

A comparative evaluation of the effect of mixing with magnesium stearate on the binding properties of filler/binders showed that all the lactose products investigated, including anhydrous α-lactose, behave in an intermediate manner, between complete plastic deformation and complete brittle fracture. For this reason there is a limited decrease in crushing strength for tablets compressed from anhydrous α-lactose, during mixing with magnesium stearate.

Some formulation examples will show that anhydrous α-lactose is a very useful filler/binder in direct compression, of which tablets with a low weight variation, sufficient strength, a low friability, a fast disintegration and a high drug release can be prepared.     

The Effect of Partice and Power Proterties on the Mechnical Properties of Directly Compressed Cellulose Tablets

The inherent material properties of four cellulose powers were evaluated and the effect of these properties on the mechnical strenght and surface hardness of direct compression tablest was studied. Two of the materials studied were the other two were experimental cellulose powers, and agglomerated cellulose and a deploymerized cellulose.

The agglomerated cellulose powder formed the strongest as well as the hardest tablets. Also both microcrystalline celluloses formed clearly stronger tablets than depolymerized cellulose, but surface hardness of the tablets compressed using these three cellulose powders was, however, quits similar.

The most important material property affecting the breaking strength of tablets was the suesific surface area of the starting material. No correlaiton between cystallinity, particle size or particule shape starting material and the strength of tablets was observed.

The surface hardness of tablets showed no simple correlation with the breaking strenth of tablets or with any single material property of cellulose powders. It is obvious, compacion could affect markeldy the hardbness of the compact surface, thus possibly masking the effect of a single material property.     

An Attempt at Bringing to Light a “Phase Inversion” in a Binary Mixture of Two Dimensional Rounded Particles

Abstract

It has been demonstrated previously in our Laboratory that the disintegrant concentration corresponding to an interparticular network between drug or diluent particles in tablets may be calculated.

When the disintegrant concentration increases little by little, for a critical concentration, a sudden modification of the physical properties of the powder mixture and of the resulting tablets can be observed.

A new structure is set up in the tablet: in a way, a “phase inversion” is produced.

This experimental critical concentration is the same as the calculated critical concentration for more or less rounded particles.

An investigation into the physical properties of binary powder mixtures and of resulting tablets is carried out when increasing, little by little, the quantity of disintegrant particles: Starches and their derivatives, cross linked PVP, are more particularly studied.

The authors study:

• – The flowing properties of powder mixtures

• – The compressibility (Hardness/Compression forces, transmission forces through the powder mixture during compression, compression cycles…)

• – The physical properties of tablets (hardness, structure hydrophilicity, disintegration time and drug dissolution).

Several formulations were studied. The results point out the setting up of the continuous network of the small particles between the larger particles for the calculated critical concentration. The same theory may be applied to the hydrophilization of powders in hard gelatin capsules and to all the more o r less rounded two dimensional particles in a mixture.     

Drug release from directly compressed tablets containing zein

Abstract

The tablets prepared by the direct compression of spray-dried particles of a drug and zein were evaluated in vitro. The release of drug from the tablets was retarded compared with drug powder alone and tablets prepared from the physical mixtures. Drug release from the tablets was controlled by changing drug content and tablet, weight.     

Comparing the Compressibility of Ludipress with the Other Direct Tableting Agents by Using Acetaminophen as an Active Ingredient

Abstract

Ludipress is a direct tableting agent which acts as an unique component, is really a multi component. In this study Ludipress compressibility and powder technological properties are compared with the other kind of DC agents (Avicel PH 102, Elcema G 250 and Elcema P 050) which are structurally based on cellulose. Acetaminophen has been chosen as an active ingredient.

The compression properties of powders and three direct tableting agent were investigated using the Heckel and Kawakita equations. Each formulations and compressed tablets which are compacted by hydraulic press with different pressure value were photographed by scanning electron microscope.

As a result Ludipress shows stable flow properties and the dilution potential of Ludipress is lower than the other DC agents.