Microcrystalline Cellulose Tablets Research Articles

Impact of immediate release film coating on the disintegration process of tablets

Pharmaceutical tablets are often coated with a layer of polymeric material to protect the drug from environmental degradation, facilitate the packaging process, and enhance patient compliance. However, the detailed effects of such coating layers on drug release are not well understood. To investigate this, flat-faced pure microcrystalline cellulose tablets with a diameter of 13 mm and a thickness between 1.5 mm to 1.6 mm were directly compressed, and a film coating layer with a thickness of 80 μm to 120 μm was applied to one face of these tablets. This tablet geometry and immediate release film coating were chosen as a model system to understand how the film coating interacts with the tablet core. The coating hydration and dissolution process was studied using terahertz pulsed imaging, while optical coherence tomography was used to capture further details on the swelling process of the polymer in the coated tablet. The study investigated the film coating polymer dissolution process and found the gelling of dissolving polymer restricted the capillary liquid transport in the core. These findings can help predict the dissolution of film coating within the typical range of thickness (30 μm to 40 μm) and potentially be extended to understand modified release coating formulations.

Effect of magnesium stearate solid lipid nanoparticles as a lubricant on the properties of tablets by direct compression

This study discusses the lubricant properties of magnesium stearate solid lipid nanoparticles (MgSt-SLN) and their effect on the tabletability, mechanical properties, disintegration, and acetaminophen-model dissolution time of microcrystalline cellulose (MCC) tablets prepared by direct compression. The behavior of MgSt-SLN was compared to reference material (RM) to identify advantages and drawbacks. The nanoprecipitation/ion exchange method was employed to prepare the MgSt-SLN. Particle size, zeta potential, specific surface area, morphology, and true density were measured to characterize the nanosystem. The MgSt-SLN particle sizes obtained were 240 ± 5 nm with a specific surface area of 12.2 m2/g. The MCC tablets with MgSt-SLN presented a reduction greater than 20 % in their ejection force, good tabletability, higher tensile strength, lower disintegration delay, and marked differences in acetaminophen dissolution when compared to the RM. The reduced particle size of the magnesium stearate seems to offer a promising technological advantage as an efficient lubricant process that does not affect the properties of tablets.

Technological Processing of Dried Powdered Rosehips to Tablets Through Wet Granulation

Abstract The pseudo-fruits of Dog Rose are a rich source of L-ascorbic acid and several other active substances, which means their high supportive therapeutic potential. The study aimed to examine the impact of the chosen technological procedure for the preparation of tablets containing rosehip powder on the amount of L-ascorbic acid in the final pharmaceutical form. Drying of the plant drug was performed at room temperature to avoid possible thermal degradation of this heat-sensitive compound. Similarly, drying of the granules after wet granulation in the oven was replaced by natural drying at room temperature. The composition of two types of prepared granule formulations differed in the filler – lactose (LAC) or microcrystalline cellulose (MCC). Apart from the disintegration test, they meet the technological requirements for granules or tablets. Lactose was confirmed as a more suitable filler, which despite the unsuccessful disintegration of the granules, ensures the disintegration of tablets within 15 minutes even without the addition of a special excipient acting as a disintegrant. The content of L-ascorbic acid detected using isotachophoresis – capillary zone electrophoresis was 87.16 ± 5.06 µg in LAC tablets and 63.33 ± 2.83 µg in MCC tablets.

Comparative evaluation of three methods for quantifying tablet brittleness

A low value of deformation before crushing is an obvious and understandable measure of brittleness of materials including tablets. In this article, three methods based on deformation measurement in a flexure tester are compared. The simplest one is a plain measurement of distance from contact or selected start point till fracture. Next the brittle-ductile method (BDI), where the distance is established by normalisation of the force–displacement curve based on the work of failure (WOF). The third method is the tablet brittleness index (TBI) by Gong and Sun, where the reciprocal of a linear distance is proposed as a brittleness quantity. The study is based on data from a previous investigation, where tablets of microcrystalline cellulose and lactose in different combinations and with four different crushing forces were utilised. The investigation shows that the BDI method is preferable. It is easy to compute without data manipulation, the sensitivity to the fracture force is negligible and it provides an independent characteristic of the brittleness of a compacted material.

Evaluation of Processing Methods for Formulated Tablets of <i>Loranthus micranthus</i>

Background: Loranthus micranthus is one of the many plants that has documented evidence of safety and efficacy in the management of many ailments and widespread use in almost every part of Nigeria. It is desirable to formulate it into a suitable dosage form for use by the populace.
 Objectives: The research was aimed at formulating the aqueous leaf extract of L. micranthus into a tablet dosage form by wet granulation and direct compression methods.
 Methods: For wet granulation method, maize starch, gelatin, polyvinyl pyrrolidone and acacia were used as binders for the formulations each was used at 2, 3, 4 and 5 % w/w concentration in the tablet. The direct compression method involved the preparation of an extract containing material (ECM). Microcrystalline cellulose, pregelatnised starch, starlac and spray dried lactose were used as filler binders for the direct compression. All the formulated tablets were assessed by comparing the crushing strength-friability ratio (CSFR) and the disintegration time (DT) to select an optimum formulation that meets both mechanical and release properties.
 Results: Using wet granulation method, maize starch and gelatin (at 3 %w/w) binder concentration as well as gelatin at 2 %w/w binder concentration produced the optimal formulations. The tablets formulated by direct compression all disintegrated within 10 min and below with microcrystalline cellulose (MCC) tablets disintegrating at 7 min. In dissolution studies, all the optimized formulations released more than 70 % of the extract within 40 min with MCC releasing up to 98 % in 30 min.
 Conclusion: Direct compression of the extract containing material produced improved tablet formulations than the wet granulation method.

Modelling the Evolution of Pore Structure during the Disintegration of Pharmaceutical Tablets

Pharmaceutical tablet disintegration is a critical process for dissolving and enabling the absorption of the drug substance into the blood stream. The tablet disintegration process consists of multiple connected and interdependent mechanisms: liquid penetration, swelling, dissolution, and break-up. One key dependence is the dynamic change of the pore space in a tablet caused by the swelling of particles while the tablet takes up liquid. This study analysed the changes in the pore structure during disintegration by coupling the discrete element method (DEM) with a single-particle swelling model and experimental liquid penetration data from terahertz-pulsed imaging (TPI). The coupled model is demonstrated and validated for pure microcrystalline cellulose (MCC) tablets across three porosities (10, 15, and 22%) and MCC with three different concentrations of croscarmellose sodium (CCS) (2, 5, and 8% w/w). The model was validated using experimental tablet swelling from TPI. The model captured the difference in the swelling behaviour of tablets with different porosities and formulations well. Both the experimental and modelling results showed that the swelling was lowest (i.e., time to reach the maximum normalised swelling capacity) for tablets with the highest CCS concentration, cCCS = 8%. The simulations revealed that this was caused by the closure of the pores in both the wetted volume and dry volume of the tablet. The closure of the pores hinders the liquid from accessing other particles and slows down the overall swelling process. This study provides new insights into the changes in the pore space during disintegration, which is crucial to better understand the impact of porosity and formulations on the performance of tablets.

Effect of Strength and Porosity of Tablets on the Magnitudes of Subdivision Forces

: In this study, a hardness tester was modified by attaching a metal blade to its testing area to obtain the minimum forces required to subdivide tablets along their diameters (F’). Moreover, the tensile strengths of subdividing tablets (TS’) were calculated. Tablets of microcrystalline cellulose (MCC) weighing 0.5 g were produced at applied compression pressures of 21, 31, 41, 50, and 60 MPa. In addition, tablets of Ludipress®, and a 5:2 mixture of paracetamol to MCC weighing 0.7 g were produced at applied compression pressures of 77, 116, 154, 193, and 232 MPa. It was found that F’ increased as the applied compression pressure used to produce the tablets increased until a maximum value was reached. This maximum value was at around 100 N for MCC and Ludipress® tablets and at around 76 N for paracetamol/MCC tablets. Moreover, a maximum value of TS’ was reached at a porosity of 0.37 for MCC, 0.15 for Ludipress®, and 0.11 for paracetamol/MCC tablets. The maximum TS’ values were at around 1.5 MPa for MCC and Ludipress® tablets and at around 0.9 MPa for paracetamol/MCC tablets. Therefore, both interparticulate bonding (tablet strength) and porosity (packing) affected the magnitudes of F’ and TS’.

Studying the dissolution of immediate release film coating using terahertz pulsed imaging

Coated tablets introduce complexity to the dissolution process, even with readily soluble immediate release coating layers. Therefore, a more detailed understanding of the physical steps involved in the dissolution process can improve the efficiency of formulation and process design. The current study uses terahertz pulsed imaging to visualise the hydration process of microcrystalline cellulose (MCC) tablet cores that were film coated with an immediate release coating formulation upon exposure to the dissolution medium. Film coated tablets that were prepared from three levels of core porosity (10%, 20% and 30%) and with coating thickness in the range of 30μm to 250μm were investigated. It was possible to resolve and quantify the distinct stages of wetting of the coating layer, swelling of the MCC particles at the core surface, and dissolution of the coating layer followed by the ingress of dissolution media into the tablet core. The liquid transport process through the coating layer was highly consistent and scalable. The penetration rate through the coating layer and the tablet core both strongly depended on coating thickness and core porosity.

Development of a novel compressed tablet-based bacterial agent for self-healing cementitious material

A novel bacterial carrier consisting of microcrystalline cellulose (MCC) tablets was developed to encapsulate spores and has 3.0 ± 0.5 × 1011 spores per dried gram, which could improve the self-healing efficiency of bacterial agents. The alkaline-resistant and spore-forming bacteria Lysinibacillus boronitolerans YS11 and Bacillus miscanthi AK13 could fill microcracks with precipitated calcium carbonate in harsh cement conditions. The MICP-capable bacteria in the tablets cured the microcracks within 7 days. The calcium carbonate on the cracks was identified via scanning electron microscopy and X-ray diffractometry, validating the MICP performance and bacterial viability. Constituting only 3% of the cement mass, the MCC-tablet allowed repairing of micro-cracks. The water permeability of mortar specimens mixed with MCC tablets steadily reduced with increasing curing ages, with crack repair rates of up to 91.1% within 28 days. Our study proved that the MCC tablets developed herein are effective carriers of bacterial spores and could thus be used for the development of self-healing cementitious material.

Particle size, compaction characteristic and tablet strength of spray-dried fermented jackfruit pulp - microcrystalline cellulose binary powder mixture

The tableting properties for fermented spray dried jackfruit (FJP) and microcrystalline cellulose (MCC) powders were studied. 25% FJP + 75% MCC, 50% FJP + 50% MCC and 75% FJP + 25% MCC binary powder mixtures were compacted into tablet form at various compaction pressures ranging from 15.1 to 73.8 MPa. The properties were compared to pure FJP and MCC tablets. The addition of MCC resulted in a higher particle size and the increased in the plastic work of the tablet. The best ratio of FJP-MCC binary tablet was found to be at 25% FJP + 75% MCC where the tablet showed the highest tensile strength. In conclusion, the addition of MCC to FJP improved the compaction characteristics and the tablet mechanical strength.

Insights on the role of excipients and tablet matrix porosity on aspirin stability.

Excipient-moisture interaction can be a critical attribute in determination of product stability. This study aimed to investigate influence of integrating excipients having different moisture interaction into moisture sensitive drug formulations. Aspirin was formulated with maize starch (MS), microcrystalline cellulose (MCC) and calcium hydrogen phosphate dihydrate (DCP). The excipients were evaluated for their inherent moisture content and water activity. Tablets fabricated at different compression pressures were exposed to 40°C, 75% relative humidity for a stipulated period before analyzing for aspirin degradation. The results revealed that while MS had higher moisture content, the water activity was relatively low. Consequently, MS tablets had lower aspirin degradation than MCC and DCP tablets. In contrast, high water activity of DCP resulted in greater aspirin degradation. This was despite the low moisture content of DCP. Influence of tablet porosity on aspirin degradation was minimal. This illustrated the fugacity of moisture, possessing high thermodynamic activity and physical spatial delimitation would not suppress its distribution. The findings suggested that excipients possessing high water retentive capacity could potentially be useful as internal tablet desiccants by acting as a moisture scavenger. This study also highlights the importance of water activity in preformulation studies related to the choice of excipients.

Influence of Various Disintegrants on the Quality of Microcrystalline Cellulose Tablets

The effects of the superdisintegrants sodium starch glycolate, croscarmellose sodium, polacrilin potassium Kyron T-314, and Amberlite IRP 88 on the quality parameters of placebo tablets prepared from microcrystalline cellulose were studied. Sodium starch glycolate was most effective with croscarmellose sodium and Amberlite IRP 88 slightly less. All studied disintegrants gave dosage forms of pharmacopoeial quality. The effects of disintegrant concentration and particle type on tablet hardness were determined. The dosage form hardness increased with increasing disintegrant content for croscarmellose sodium with fibrous particles and decreased for sodium starch glycolate and polacrilin potassium with round and irregularly shaped particles. The tablets were harder if polacrilin potassium was added to the formulation.

Preparation and assessment of poly(methacrylic acid-coethylene glycol dimethacrylate) as a novel disintegrant

Purpose: To prepare and evaluate poly(methacrylic acid (MAA)-co-ethylene glycol dimethacrylate (EGD)) as a tablet disintegrant. Methods: Poly(MAA-co-EGD) in acid (H) and sodium (Na) forms at cross-linker (EGD) levels of 0.25 -16 % were synthesized and subjected to Fourier transform infrared spectroscopy. Swelling capacity, disintegration efficiency and cytotoxicity to Caco-2 cells were determined using standard procedures. Results: Poly(MAA-co-EGD) in acid (H) and sodium (Na) forms were successfully prepared. In contact with water, the polymers in Na form swelled more than those in H form. The swelling capacities of polymers in H and Na forms decreased with increasing amounts of cross-linker. Incorporation of the polymers accelerated the disintegration of microcrystalline cellulose tablets (placebo), and the disintegration efficiency depended on the salt form and amount of cross-linker. The Na salt form of the polymer crosslinked at 16 % EGD was the best candidate disintegrant. When used at 2.5 and 10 %, the selected polymer effectively promoted the disintegration and drug release of propranolol hydrochloride tablets. Moreover, cytotoxicity tests showed that it was non-toxic to Caco-2 cells. Conclusion: The developed poly(MAA-co-EGD) possesses good disintegration and dissolution functionalities. Thus, it may be adopted as a new super-disintegrant for fast-release tablets. Keywords: Tablet disintegrant, Methacrylic acid, Ethylene glycol dimethacrylate, Propranolol hydrochloride

Cavities spatial distribution confined by microcrystalline cellulose particles determines tablet disintegration patterns

Cavities and the architectures inside tablet play a decisive role for the permeation of water within tablet to initiate disintegration phenomenon. The present study aims to establish inner structure characterization methodology based on synchrotron radiation X-ray microcomputed tomography (SR-μCT) for microcrystalline cellulose (MCC) tablets and to correlate the cavities and 'their attributes to tablet disintegration phenomenon. The three-dimensional (3D) morphological architecture and quantitative data of single particles for 12 specifications of MCC, and respective MCC tablets' cavities structure were obtained through advanced SR-μCT studies. The image processing techniques were established to study the morphology of voids and porosity in an axial and radial direction based on the highly resolved 3D structure of tablets. The in-situ visualization of morphological disintegration behavior indicates that there were two patterns of disintegrations, which can be cataloged as laminating type (LT) and splitting type (ST) disintegrations. The principal component analysis (PCA) was used for multivariate data analysis to get the meaningful correlation among disintegration behaviors, cavities morphology, single particles attributes, and the cavities spatial arrangement within the tablets. These findings have deepened insights into inner structures of tablets and single particle structural attributes to tablet disintegration, reflecting the mechanism of disintegration mode, and the significance of pharmaceutical structure evaluated via SR-μCT.

The Effects of Fillers and Binders on the Accuracy of Tablet Subdivision.

The effects of excipients on the accuracy of tablet subdivision are severely underinvestigated. In this study, placebo tablets were prepared using a combined mixture design of fillers and binders to evaluate the effect of these excipients on subdivision accuracy. The responses assessed were mass loss, mass variation, tablet fragmentation, and increased friability. Dicalcium phosphate dihydrate (DCP) gave rise to more uniform and denser tablets than microcrystalline cellulose (MCC), thus resulting in greater subdivision accuracy. The binder type, hydroxypropylcellulose (HPC) or polyvinylpyrrolidone (PVP), did not affect the subdivision of DCP tablets. On the contrary, the structural similarity between HPC and MCC led to improved subdivision accuracy for MCC tablets. A less accurate subdivision was observed in tablets prepared with a DCP-MCC combination; this finding could be attributed to irregular binder distribution in this matrix. An optimized response was built using desirability analysis. This study helps to illuminate the relationship between fillers and binders to guide formulation scientists in the development of tablets with better subdivision performance.

On Identification of Critical Material Attributes for Compression Behaviour of Pharmaceutical Diluent Powders.

As one of the commonly-used solid dosage forms, pharmaceutical tablets have been widely used to deliver active drugs into the human body, satisfying patient’s therapeutic requirements. To manufacture tablets of good quality, diluent powders are generally used in formulation development to increase the bulk of formulations and to bind other inactive ingredients with the active pharmaceutical ingredients (APIs). For formulations of a low API dose, the drug products generally consist of a large fraction of diluent powders. Hence, the attributes of diluents become extremely important and can significantly influence the final product property. Therefore, it is essential to accurately characterise the mechanical properties of the diluents and to thoroughly understand how their mechanical properties affect the manufacturing performance and properties of the final products, which will build a sound scientific basis for formulation design and product development. In this study, a comprehensive evaluation of the mechanical properties of the widely-used pharmaceutical diluent powders, including microcrystalline cellulose (MCC) powders with different grades (i.e., Avicel PH 101, Avicel PH 102, and DG), mannitol SD 100, lactose monohydrate, and dibasic calcium phosphate, were performed. The powder compressibility was assessed with Heckel and Kawakita analyses. The material elastic recovery during decompression and in storage was investigated through monitoring the change in the dimensions of the compressed tablets over time. The powder hygroscopicity was also evaluated to examine the water absorption ability of powders from the surroundings. It was shown that the MCC tablets exhibited continuous volume expansion after ejection, which is believed to be induced by (1) water absorption from the surrounding, and (2) elastic recovery. However, mannitol tablets showed volume expansion immediately after ejection, followed by the material shrinkage in storage. It is anticipated that the expansion was induced by elastic recovery to a limited extent, while the shrinkage was primarily due to the solidification during storage. It was also found that, for all powders considered, the powder compressibility and the elastic recovery depended significantly on the particle breakage tendency: a decrease in the particle breakage tendency led to a slight decrease in the powder compressibility and a significant drop in immediate elastic recovery. This implies that the particle breakage tendency is a critical material attribute in controlling the compression behaviour of pharmaceutical powders.

Effect of particle size and diluent type on critical parameters for disintegration of tablets containing croscarmellose sodium as a disintegrant

Purpose: The aim of the present work was to determine the effect of particle size and type of diluents on critical concentration for the disintegration of tablet formulations containing a physical binary mixture of a superdisintegrant (croscarmellose sodium, CS) and a diluent.Methods: The diluents used in this study were microcrystalline cellulose (MCC), dibasic calcium phosphate (DCP) and pregelatinized starch (PGS). Each diluent was divided into 2 different size ranges (small and large size)) and further mixed with 0 - 100 % CS. The binary mixture was compressed at controlled pressure, and the disintegration time and physical characteristic of the tablets were evaluated.Results: The point of CS concentration that markedly affected the disintegration time of the tablets was recorded as the critical concentration for disintegration. The results showed that the particle size of the diluent did not affect the disintegration time. The critical CS concentrations were 2 % for DCP and MCC tablets and 5 % for PGS tablet. Adding a small amount of CS improved the disintegration of the tablets. However, increasing the amount of CS in the formulation also affected the hardness of the tablets. The particle size of diluents had a significant effect on the critical concentration for tablet disintegration.Conclusion: Determining the type and appropriate amounts of diluent and disintegrant (percolating component) may be useful in the design of tablet formulations.Keywords: Disintegration, Percolation threshold, Croscarmellose sodium, Microcrystalline cellulose, Dibasic calcium phosphate, Pre-gelatinized starch

A Simplified Model of Moisture Transport in Hydrophilic Porous Media With Applications to Pharmaceutical Tablets

This work establishes a predictive model that explicitly recognizes microstructural parameters in the description of the overall mass uptake and local gradients of moisture into tablets. Model equations were formulated based on local tablet geometry to describe the transient uptake of moisture. An analytical solution to a simplified set of model equations was solved to predict the overall mass uptake and moisture gradients with the tablets. The analytical solution takes into account individual diffusion mechanisms in different scales of porosity and diffusion into the solid phase. The time constant of mass uptake was found to be a function of several key material properties, such as tablet relative density, pore tortuosity, and equilibrium moisture content of the material. The predictions of the model are in excellent agreement with experimental results for microcrystalline cellulose tablets without the need for parameter fitting. The model presented provides a new method to analyze the transient uptake of moisture into hydrophilic materials with the knowledge of only a few fundamental material and microstructural parameters. In addition, the model allows for quick and insightful predictions of moisture diffusion for a variety of practical applications including pharmaceutical tablets, porous polymer systems, or cementitious materials.

Lubricant sensitivity in function of paddle movement in the forced feeder of a high-speed tablet press

Context: The negative impact of magnesium stearate (MgSt) on the hardness of tablets is a well-known phenomenon, but the influence of paddle movement in the forced feeder on the lubricant effect during tablet compression is often neglected.Objective: The purpose of this research was to investigate the influence of paddle speed in the forced feeder on tablet tensile strength (TS).Materials and methods: Mixtures of microcrystalline cellulose (MCC) and MgSt (0.5%) were blended using different methods (low & high shear). After blending, the formulations were compressed into tablets. All parameters of the tableting cycle were kept constant except the speed of the paddles in the forced feeder.Results and discussion: The blending technique affected the sensitivity of the formulation to the paddle speed. The TS of pure MCC tablets did not change in function of paddle speed, while tablets prepared by low shear mixing became softer at higher paddle speed. The TS of tablets manufactured using the high-shear mixed blend was low and did not vary in function of paddle speed, suggesting that overlubrication already occurred during the initial blending step. Furthermore, analysis of the machine parameters allowed evaluation of the influence of the paddles on the flowability, initial packing, and compactability of the powder mixtures.Conclusion: The results elucidated that during manufacturing of tablets using MgSt-containing blends care should not only be taken during the blending step prior to tableting, but also during the tableting process itself, as paddle speed can affect tablet TS, a critical quality attribute.

A terahertz time-domain study on the estimation of opto-mechanical properties of pharmaceutical tablets using the Hashin–Shtrikman bounds for refractive index: a case study of microcrystalline cellulose and starch acetate compacts

This work highlights the use of Hashin–Shtrikman (H–S) bounds in the prediction and verification of the effective refractive index, the height and the Young’s modulus of given training sets of pharmaceutical compacts using the measured time delay of a THz pulse traversing the compacts. Set A consisted of 13 microcrystalline cellulose (MCC) compacts whereas set B was made up of 5 starch acetate (SA) compacts. MCC is a typical ingredient of many pharmaceutical tablets. In the case of the MCC compacts, tight and closely matched bounds were obtained between the experimental, the calculated upper, lower bound values for the effective refractive index, and the height values. This promising outcome has shown the high possibility of utilizing H–S bounds in the verification and prediction of the decision level of useful parameters, which can serve as a quality check for pharmaceutical tablets. For the SA compacts, although less tight bounds were observed, the experimental values for the effective refractive index and the Young’s modulus were closely matched with the upper and the lower bounds, respectively. We therefore speculate based on the above observations that the MCC tablets contain an almost evenly distributed spherically shaped air voids whereas in the SA compacts, this assumption might not necessary be true.