Capping Tendency Research Articles

Development of a simple in-die method for determination of capping tendency in rotary tableting machines.

A rotary tableting machine is used for the continuous tableting process. Tableting conditions often result in capping, leading to serious problems during production. Several studies have been conducted to predict the tablet capping tendency. However, as most previous studies were conducted using a compaction simulator, there is a lack of technology that can be readily applied during actual production. Therefore, the present study aimed to develop a novel method for predicting tablet capping in a rotary tableting machine. We hypothesized that capping occurs when residual stress of the tablet inside a die exceeds the critical stress immediately before ejection. Residual stress was evaluated by measuring the in-line die-wall pressure in a rotary tableting machine. Additionally, critical stress was estimated from the tablet strength inside the die using the Rumpf's equation. The critical and residual stresses were compared to determine the capping tendency to some extent. The findings of this study will substantially contribute to the rapid detection of tablet capping during tablet production.

Assessing the Impact of Punch Geometries on Tablet Capping Using a Newly Proposed Capping Index.

Increased tablet anisotropy could lead to increased tablet capping propensity. Tooling design variables such as cup depth could serve as a key player for inducing tablet anisotropy. A new capping index (CI) consisting of the ratio of compact anisotropic index (CAI) and material anisotropic index (MAI) is proposed to evaluate tablet capping propensity as a function of punch cup depth. CAI is the ratio of axial to radial breaking force. MAI is the ratio of axial to radial Young's modulus. The impact of various punch cup depths [flat face, flat face beveled edge, flat face radius edge, standard concave, shallow concave, compound concave, deep concave, and extra deep concave] on the capping propensity of model acetaminophen tablets was studied. Tablets were manufactured at 50, 100, 200, 250, and 300MPa compression pressure at 20 RPM on different cup depth tools using Natoli NP-RD30 tablet press. A partial least squares model (PLS) was computed to model the impact of the cup depth and compression parameters on the CI. The PLS model exhibited a positive correlation of increased cup depth to the capping index. The finite elemental analysis confirmed that a high capping tendency with increased cup depth is a direct result of non-uniform stress distribution across powder bed. Certainly, a proposed new capping index with multivariate statistical analysis gives guidance in selecting tool design and compression parameters for robust tablets.

Effects of Capping Agents on Shape, Stability, and Oxygen Evolution Reaction Activity of Copper Nanoparticles

Here, five different capping agents’ polyethylene glycol (PEG), cetyltrimethylammonium bromide (CTAB), polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), and oleylamine (OAm) are used to form copper nanoparticles (Cu-NPs), along with their electrocatalytic oxygen evolution reaction (OER) properties. The produced Cu-NPs’ mono-dispersity and their interactions with PEG, CTAB, PVA, PVP, and OAm were examined. The mean particle size determined by TEM images for the uncapped Cu-NPs as generated, PVA-capped, PVP-capped, CTAB-capped, PEG-capped, and OAm-capped samples, respectively, were 2.71 nm, 2.22 nm, 3.10 nm, 3.31 nm, 1.49 nm, and 1.71 nm. Greater than prepared catalysts, commercial Pt/C has a 3.7 nm size. It’s interesting to note that the CTAB-capped Cu-NPs considerably exhibit the strongest OER activity, with a very low overpotential of 222 mV at 10 mA cm−2, lower than many previously reported and the high electrocatalytic activity for OER of the commercial RuO2 catalysts. However, an expedited stress experiment shows that the CTAB-capped NPs have greater structural stability during electrochemical cycling. Their strong capping tendency and particle shape are the key causes of this. The approach for creating Cu nanocatalysts described in this paper has several potential uses for the creation of bimetallic catalysts.

Characterization of Tableting Speed-Dependent Deformation Properties of Active Pharmaceutical Ingredients in Powder Mixtures Using Out-of-Die Method.

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.

Quantitative Evaluation for the Effect of Tableting Speed on Compression Behavior of Pharmaceutical Powders using a Rotary Tablet Press

The purpose of this study is to evaluate the effect of tableting speed on the compression behavior of pharmaceutical powders using an R&D rotary tablet press. Cilostazol, probucol and ibuprofen were selected as model drugs, and they were mixed at a mass concentration of 20% into two base formulations composed of different excipients. The tablets were prepared at two levels of turret rotation speeds of 20 rpm and 60 rpm, and the physical properties of the tablets were evaluated. As a result, placebo tablets and cilostazol tablets had no effect on the tableting speed. However, the compressibility of probucol and ibuprofen tablets decreased and the capping tendency was observed, although the compactibility was not affected. The strain rate sensitivity (SRS) index was obtained from an out-of-die Heckel analysis, which was used to quantitatively evaluate the effect of tableting speed on the compressibility. It was found that the R&D rotary tablet press was possible to evaluate the compressibility and capping tendency by the SRS index.

Shear strength of pharmaceutical tablets: Theoretical considerations, evaluation and relation with the capping tendency of biconvex tablets

Capping is a major industrial issue during pharmaceutical powder compression, especially in the case of biconvex tablets. Several articles proposed that capping was in fact a failure in shear. Shear strength should thus be interesting to study the capping tendency of a formulation. In this work, the ratio between the shear strength and the tensile strength obtained by diametral compression was first studied from a theoretical point of view considering different failure criteria. Then, a shear test usually performed on bilayer tablets was adapted to monolayer tablets. The shear strength obtained for 5 products, 2 of them having a known capping tendency, were compared with the strengths obtained during diametral compression test and uniaxial compression test.The results indicated that, for the formulations with a capping tendency, the ratio between the shear strength and diametral compression strength was lower than for the other products. Considering the mechanism of capping, the weakness in shear of these formulations explained their capping tendency. This was also linked with the mechanical anisotropy of the same formulations which was shown in the literature. In the cases studied in this article, the fundamental reason for the capping tendency was the anisotropic strength of the tablets.

Gaining insight into tablet capping tendency from compaction simulation

Capping or lamination is an unsolved common problem in tablet manufacturing. Knowledge gaps remain despite an enormous amount of effort made in the past to better understand the tablet capping/lamination phenomenon. Using acetaminophen – containing formulations, we examined the potential use of a compaction simulator as a material-sparing tool to predict capping occurrence under commercial tableting conditions. Systematical analyses of the in-die compaction data led to insight on the potential mechanism of tablet capping/lamination. In general, capping strongly correlates with high in-die elastic recovery, high Poisson’s ratio, low tensile strength, and radial die-wall pressure. Such insight can be used to guide the formulation design of high quality tablet products that are free from capping problems for challenging active pharmaceutical ingredients.

Influence of the Punch Head Design on the Physical Quality of Tablets Produced in a Rotary Press

This study aims to investigate the influence of tablet punch head design on compaction and the resultant tablet mechanical properties. Tablets were prepared using flat-face punches with different head flat and head radius configurations, on a rotary tablet press with compression rolls of different diameters. The results showed that tablets produced using punches with head flats consistently displayed higher tensile strengths and lower capping tendencies. Exclusion of the head flat in the punch head geometry caused the compacts to undergo a state of continual deformation during the compaction cycle, possibly with increasing elasticity without the opportunity for more prolonged stress relaxation. Extension of head flat diameter produced small increments in dwell time and this could bring about significant improvements to the tablet mechanical quality. Changes to the punch head radius were found only to affect the compression profiles marginally, but this only produced insignificant differences in the tablet mechanical properties. A smaller compression roll allowed greater plastic flow during the dwell phase, but this was insufficient to effectively counteract the adverse effects due to increased strain rate during the consolidation phase, leading to deterioration of tablet mechanical quality.

Evolution of the Die-Wall Pressure during the Compression of Biconvex Tablets: Experimental Results and Comparison with FEM Simulation

Capping is a classical manufacturing problem for tablets, which is known to affect more biconvex tablets than flat-faced ones. One reason could be the development of a higher residual die-wall pressure during unloading. Unfortunately, contradictory results were published on the subject. In this work, the evolution of the die-wall pressure during the compaction of biconvex tablets was studied experimentally and using finite element method (FEM) modeling. It was compared with the case of flat-faced tablets. Experimental and numerical results showed that during the compression of biconvex tablet, a lower maximum die-wall pressure and a higher residual die-wall pressure were obtained compared with the case of flat-faced tablet. Moreover, both approaches showed, for biconvex tablets, a temporary increase of the die-wall pressure at the end of the unloading phase. FEM demonstrated that this phenomenon was due to a gradual loss of contact between the punch and the tablet from the side to the center. This complex unloading behavior causes the temporary increase of the die-wall pressure and the development of a shear stress between the convex part and the land of the tablet. This could explain the capping tendency of biconvex tablets.

Numerical evaluation of the capping tendency of microcrystalline cellulose tablets during a diametrical compression test

Capping is one of the major problems that occur during the tabletting process in the pharmaceutical industry. This study provided an effective method for evaluating the capping tendency during diametrical compression test using the finite element method (FEM). In experiments, tablets of microcrystalline cellulose (MCC) were compacted with a single tabletting machine, and the capping tendency was determined by visual inspection of the tablet after a diametrical compression test. By comparing the effects of double-radius and single-radius concave punch shapes on the capping tendency, it was observed that the capping tendency of double-radius tablets occurred at a lower compaction force compared with single-radius tablets.Using FEM, we investigated the variation in plastic strain within tablets during the diametrical compression test and visualised it using the output variable actively yielding (AC YIELD) of ABAQUS. For both single-radius and double-radius tablets, a capping tendency is indicated if the variation in plastic strain was initiated from the centre of tablets, while capping does not occur if the variation began from the periphery of tablets. The compaction force estimated by the FEM analysis at which the capping tendency was observed was in reasonable agreement with the experimental results.

Crystal coating via spray drying to improve powder tabletability

A continuous crystal coating method was developed to improve both flowability and tabletability of powders. The method includes the introduction of solid, dry particles into an atomized spray during spray drying in order to coat and agglomerate individual particles. Paracetamol was used as a model drug as it exhibits poor flowability and high capping tendency upon compaction. The particle size enlargement and flowability were evaluated by the mean median particle size and flow index of the resulting powders. The crystal coating coprocessing method was successful for the production of powders containing 75% paracetamol with excellent tableting properties. However, the extent of agglomeration achieved during coprocessing was limited. Tablets compressed on a rotary tablet press in manual mode showed excellent compression properties without capping tendency. A formulation with 75% paracetamol, 5% PVP and 20% amorphous lactose yielded a tensile strength of 1.9MPa at a compression pressure of 288MPa. The friability of tablets compressed at 188MPa was only 0.6%. The excellent tabletability of this formulation was attributed to the coating of paracetamol crystals with amorphous lactose and PVP through coprocessing and the presence of brittle and plastic components in the formulation. The coprocessing method was also successfully applied for the production of directly compressible lactose showing improved tensile strength and friability in comparison to a spray dried direct compression lactose grade.

Quantitative Correlation of the Effect of Process Conditions on the Capping Tendencies of Tablet Formulations

Capping is a mechanical defect in tablet formulation and manufacture. Understanding what influences tablet capping in terms of process variables and formulation properties and developing specialized techniques to correlate these variables with mechanical failures are practical interests of the pharmaceutical industry. Tablet compression emulator was used to rank order capping tendencies of a diverse sample set. The compression forces of 5-25 kN were used to compress round, beveled edge, and oval shape tablets. Compression speeds of 25, 40, and 80 rpm were chosen as representative ranges for bench-to-manufacturing-scale processing. Tablets were tested by in-house developed nondestructive ultrasonic method. The measurements revealed that elastic modulus vary with different testing orientations that indicated elastic modulus anisotropy in tablets. It was shown that altering process conditions such as tooling, compression force, and compression speed significantly impact the capping tendencies of formulations. A systematic approach has been applied to develop a predictive tool to assess capping tendencies of formulations. The developed tool is fast, material sparing, and has potential to flag the risk of manufacturability issues and provide insight into the performance of formulations during early development.

The effect of punch's shape on die compaction of pharmaceutical powders

This paper investigates the compaction of pharmaceutical powders using different shapes of punches. We introduce a model of mechanical behaviour Drucker–Prager Cap (DPC), using the approach of compressible continuous media. The model parameters that are depending on the material density, were identified from experimental data and a calibration process was applied on Microcrystalline Cellulose (MCC) powder. In addition, the mathematical formulation of the boundary problem of compaction in rigid tools brings back to an optimization problem with constraint, which is solved by finite element method. The Drucker–Prager Cap model, which is implemented in Abaqus/Standard software, was employed using a user subroutine, USDFLD. Three kinds of typical pharmaceutical tablets are considered: flat-face tablet and concave face tablet with two different depths. Results of simulations of die compaction cycle as compression, decompression and ejection, reproduce the powder compaction process for the studied shaped punches. The effects of the punch's shape on the compaction process were observed on the distribution and the maximum of stress and density in the compact. Examination of the density gradient according to the shape, suggests a capping tendency, which increases with the punch depth. This study illustrates the potentiality of the FEM method, which could be used as an efficient tool to predict the density and the stress distributions into shaped compacts and to provide a diagnostic of the capping problems.

Development of predictive tools to assess capping tendency of tablet formulations

Capping is one of the mechanical defects in the tableting process in which catastrophic failure of the compact can occur. Understanding what influences tablet capping in terms of process variables, material properties, and density/stress distributions in tablets and developing specialized techniques to correlate these variables with mechanical failures are practical interests of the pharmaceutical industry. In this article, a nondestructive ultrasonic method as well as a derived Cap Value to predict the capping tendencies of tablet formulations was developed. In the ultrasonic method, effective elastic (E) and shear (G) moduli of each tablet in axial and radial directions were characterized. The ultrasonic measurements revealed that elastic and shear modulus values vary with different testing orientations which indicated elastic and shear moduli anisotropy in tablets. The anisotropic properties of tablet formulations are represented by a dimensionless value (EG). It was found that as the EG ratio decreases; the compressed powder exhibited an increasing level of anisotropic nature, which led to a higher tendency for capping. A formulation with a higher Cap Value seemed to have a higher likelihood for capping. Acceptance criteria of the Cap Value and EG ratio have been proposed based on manufacturing performance. A systematic approach has been applied to develop predictive tools to assess capping tendencies of formulations. These tools have been shown to correlate well with actual capping performance of a diverse sample set. The developed tools are fast, material sparing and have potential to flag the risk of capping issues and provide insight into the performance of common materials during formulation and process development. Application of these tools may help reduce development time, API usage and facilitate development of a robust product.

In-Die Evaluation of Capping Tendency of Pharmaceutical Tablets Using Force-Displacement Curve and Stress Relaxation Parameter

A novel in-die evaluation method of tablet capping tendency was proposed based on a force-displacement curve and stress relaxation parameter in a tableting process. In our previous study (Chem. Pharm. Bull., 59, 2011, Nakamura et al.), the phase diagram consisting of elastic recovery energy (E(e)) and plastic deformation energy (E(p)) of compressed powder, named as the E(e)-E(p) diagram, was proposed. However, it was found that capping tendency of tablets prepared by double-compression with multi-component powder formulations cannot be discriminated using the E(e)-E(p) diagram. To improve the capping discrimination ability, we here proposed a novel corrected phase diagram consisting of the E(e) and an interparticle bonding parameter E(b)(t), named as the E(e)-E(b)(t) diagram. The E(b)(t) was proposed as a new parameter expressing strength of the interparticle bonding formed by the stress relaxation inside compressed powder. The E(b)(t) was defined as a product of the E(p) and the stress relaxation parameter Y(t), estimated from the force-displacement curve and the stress relaxation test. The capping discrimination ability of the diagrams was evaluated using a hierarchical-clustering analysis. The results exhibited that the capping tendency could be clearly discriminated using the proposed E(e)-E(b)(t) diagram at the double-compression and the multi-component powder formulations, as compared to the E(e)-E(p) diagram. This proposed diagram can be used for screening of the powder formulations to avoid the capping.

Roll compaction as a dry granulation method for paracetamol

Paracetamol was selected as a model drug and roll compaction was examined in an attempt to improve the undesirable physical characteristics of paracetamol. Furthermore, the impact of tableting speed was investigated with respect to the tablet tensile strength and capping tendency. The results showed that roll compaction could successfully correct the poor flowability of paracetamol-containing powder blend. Roll pressure and roll speed during roll compaction had particularly significant effects on the granule and tablet properties. Tablet tensile strength was decreased but it was still in an acceptable range. No significant change was observed in compressibility, compactibility and drug release pattern. No polymorphic change occurred. The material showed the lower speed dependency in tableting after roll compaction. There was no considerable difference in capping tendency between starting powder and roll-compacted granules.

Development of a Novel Tablet Machine for a Tiny Amount of Powder and Evaluation of Capping Tendency

A novel single punch tablet machine was developed for a tiny amount of powder sample. This tablet machine mainly consists of upper and lower punches, single die, and conical powder feeder equipped with micro-vibrators. By using the powder feeder, mass of discharged powder can be maintained constant even if a tiny amount of powder having poor flowability is used. Motions of both upper and lower punches can be set arbitrarily. Thus, this machine enables us to prepare tablets with a tiny amount of powder sample under the same compression mechanism as conventional rotary tablet machines. Performance of the developed tablet machine was evaluated in a continuous direct tableting using a model powder with poor flowability. Thirty-four tablets (195 mg×34) having acceptable properties can be successfully prepared using no more than 10.0 g of a powder sample. We then proposed a novel in-die evaluation method of capping tendency. A new phase diagram consisting of the elastic recovery energy and the plastic deformation energy was proposed. These energies were calculated from a force-displacement profile, continuously monitored by the developed tablet machine. The results indicate that by using the new diagram the capping tendency of tablets prepared from various model powders can be well discriminated. The developed tablet machine and proposed evaluation method can contribute to a significant cost reduction and speeding up of formulation studies of oral dosage form.

Minimisation of the capping tendency by tableting process optimisation with the application of artificial neural networks and fuzzy models

The pharmaceutical industry is increasingly aware of the advantages of implementing a quality-by-design (QbD) principle, including process analytical technology, in drug development and manufacturing. Although the implementation of QbD into product development and manufacturing inevitably requires larger resources, both human and financial, large-scale production can be established in a more cost-effective manner and with improved efficiency and product quality. The objective of the present work was to study the influence of particle size (and indirectly, the influence of dry granulation process) and the settings of the tableting parameters on the tablet capping tendency. Artificial neural network and fuzzy models were used for modelling the effect of the particle size and the tableting machine settings on the capping coefficient. The suitability of routinely measured quantities for the prediction of tablet quality was tested. Results showed that model-based expert systems based on the contemporary routinely measured quantities can significantly improve the trial-and-error procedures; however, they cannot completely replace them. The modelling results also suggest that in cases where it is not possible to obtain sufficient number of measurements to uniquely identify the model, it is beneficial to use several modelling techniques to identify the quality of model prediction.

Influence of dry granulation on compactibility and capping tendency of macrolide antibiotic formulation

The effect of dry granulation (roller compaction and slugging) on compactibility and tablet capping tendency in a formulation with macrolide antibiotic and microcrystalline cellulose (MCC) was investigated. Direct tableting of this formulation revealed a pronounced capping tendency. Both dry granulated systems exhibit better compactibility and significant reductions in capping tendency compared to direct tableting. The capping tendency was also reduced through the use of precompression during direct tableting. The main volume reduction mechanism for macrolide antibiotic is fragmentation; this was confirmed by Heckel analysis, the lubricant sensitivity test, and SEM images. The yield pressure ( P y) of the direct tableting system is lower than the P y of dry granulated systems, which indicates the lower plasticity of dry granulated systems. These findings do not explain the lower capping tendency of dry granulated systems compared to direct tableting. The main differentiating bonding mechanism is attributed to long distance intermolecular bonds due to the intense amorphization of macrolide antibiotic that occurs during dry granulation. Amorphization leads to a significant increase in surface free energy and consequently stronger long distance bonding between particles, which can withstand elastic relaxation and therefore reduce the capping problem. Solid bridges probably do not make a notable contribution to the mechanical strength of tablets, due to the brittle nature of the particles and the complex molecular structure of macrolide antibiotic.

English

A comparative study has been carried out to investigate the binder effects of the gums ofCissus populnea&nbsp;and&nbsp;Accasia senegal&nbsp;on the mechanical properties of paracetamol tablets. Tablet mechanical properties evaluated include the packing fraction (Pf), the tensile strength (T) and the brittle fracture tendency (BFI). Varying concentrations of the gum mucilage ranging from 1 - 15% (w/v) was prepared and their relative viscosities determined. Each concentration was used to wet massed paracetamol powder to form granules. Tablets of paracetamol (500 &plusmn; 6.5 mg) were compressed at a constant compression load (7 arbitruary units on the scale). The tablets were equilibrated for 24 h before evaluation. At all binder concentrations&nbsp;A.&nbsp;senegal&nbsp;gum produced harder and more consolidated tablets than&nbsp;C.&nbsp;populnea&nbsp;as reflected by the higher T and Pf&nbsp;values respectively. For instance, the T and Pf&nbsp;values of the tablets at binder concentration of 10% (w/v) were 0.69 MNm-2&nbsp;and 0.47 (A.&nbsp;senegal) and 0.57 MNm-2&nbsp;and 0.23 (C.populnea), respectively. On the contrary, an increase in binder concentration generally resulted in a decrease in BFI values and this decrease was more marked with&nbsp;C.populnea. The study showed that&nbsp;A.&nbsp;senegal&nbsp;mucilage displayed better tableting characteristics and higher tendency for ameliorating capping tendency. Both mucilages have the potentials for substitution as binder for the more expensive starches in tablet formulation. &nbsp; Key words:&nbsp;Cissus populnea,&nbsp;Acassia senegal&nbsp;gum, paracetamol tablet, tensile strength, brittle fracture index, packing fraction, binder effect.