Evaluation of tablet formation of different lactoses by 3D modeling and fractal analysis

The aim of this study was to use 3D modeling to differentiate not only among the four different types of lactose alpha-lactose monohydrate, spray-dried lactose, agglomerated lactose and lactose anhydrous but also between products from different manufacturers. Further "box-counting" fractal analysis of SEM images was done to gain additional information on tableting characteristics and tablet properties which can be found in the fractal structure. Twelve different materials from different manufacturers were analyzed for their powder-technological and physicochemical properties. They were tableted on an eccentric tableting machine at graded maximum relative densities and the recorded data, namely force, time, and displacement were analyzed by the 3D modeling technique. Tablet properties such as, elastic recovery, crushing force and morphology were analyzed. The results show that 3D modeling can precisely distinguish deformation behavior for different types of lactose and also for the same type of material produced with a slightly different technique. Furthermore, the results showed that the amorphous content of the lactose determined the compactibility of the material, which is due to a reversible exceeding of the glass transition temperature of the material. The three fractal dimensions DBW (box surface dimension), DWBW (pore/void box mass dimension), and DBBW (box solid mass dimension) are capable of describing morphological differences in lactose materials. Multivariate regression analysis showed that the fractal surface structure of the lactose-based materials is strongly correlated to tableting characteristics and tablet properties. Especially with regards to 3D modeling, it was found that the fractal indices can describe the parameters time plasticity d, pressure plasticity e, and fast elastic decompression, which is the inverse of omega. In addition, the 3D parameters are able to describe the powder and tablet fractal indices. In conclusion, the 3D modeling is not only able to characterize the compression process but it can also provide information on the final tablet morphology.     

Spray-Dried Rice Starch: Comparative Evaluation of Direct Compression Fillers

Spray-dried rice starch (SDRS), microcrystalline cellulose (MCC), lactose (L), pregelatinized starch (PS), and dibasic calcium phosphate (DCP) were studied for their flow behaviors and tableting properties. Both flow rate and percent compressibility values indicated that SDRS exhibited excellent flowability. The increase in magnesium stearate content reduced the hardness of MCC and SDRS tablets; however, general tablet properties were still acceptable while the PS tablets were unsatisfactory at high lubricant concentrations. The hardness of L or DCP tablets was not affected by the lubricant. The disintegration of L tablets was prolonged with the increased lubricant concentration while that of PS tablets seemed to be decreased due to softened tablets. The disintegration times of MCC and SDRS tablets seemed to be independent of the lubricant added. With respect to the dissolution, SDRS-based tablets offered fast and complete release of the drug regardless of its solubility. SDRS, L, and DCP exhibited comparable carrying capacity for ascorbic acid. The best dilution potential was obtained with MCC while the worst was obtained with PS.     

Spray-Dried Rice Starch: Comparative Evaluation of Direct Compression Fillers

Abstract

Spray-dried rice starch (SDRS), microcrystalline cellulose (MCC), lactose (L), pregelatinized starch (PS), and dibasic calcium phosphate (DCP) were studied for their flow behaviors and tableting properties. Both flow rate and percent compressibility values indicated that SDRS exhibited excellent flowability. The increase in magnesium stearate content reduced the hardness of MCC and SDRS tablets; however, general tablet properties were still acceptable while the PS tablets were unsatisfactory at high lubricant concentrations. The hardness of L or DCP tablets was not affected by the lubricant. The disintegration of L tablets was prolonged with the increased lubricant concentration while that of PS tablets seemed to be decreased due to softened tablets. The disintegration times of MCC and SDRS tablets seemed to be independent of the lubricant added. With respect to the dissolution, SDRS-based tablets offered fast and complete release of the drug regardless of its solubility. SDRS, L, and DCP exhibited comparable carrying capacity for ascorbic acid. The best dilution potential was obtained with MCC while the worst was obtained with PS.     

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

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.     

Comparative compaction properties of various Microcrystalline Cellulose types and Generic Products

The purpose of this review is to compare the tableting properties of conventional microcrystalline cellulose (MCC) with those of other common direct compression diluents and of the numerous new MCC grades and brands recently made available. After a brief discussion of the mechanisms of consolidation involved in the formation of MCC tablets, the first section deals with the basic mechanical properties of powders important for compression. Values of parameters describing ductility, brittleness, elasticity and viscoelasticity are presented and discussed in relation with the degree of polymerization, the crystallinity, the moisture content and the morphological properties of the materials.

The tableting properties of the powders during the compression process (densification behavior, work of compression) and the mechanical strength of the finished products (compactibility) are examined. Special attention is given to the effects of moisture content, lubricants and other added substances on the performances of MCC products. Comparative tablet weight variation data are provided for several MCC types from different supplies.

Finally, aging of the MCC compacts is discussed in relation to environmental conditions, before warning the user in the conclusion on the considerable variability of MCC products currently available on the market.     

Comparative compaction properties of various Microcrystalline Cellulose types and Generic Products

Abstract

The purpose of this review is to compare the tableting properties of conventional microcrystalline cellulose (MCC) with those of other common direct compression diluents and of the numerous new MCC grades and brands recently made available. After a brief discussion of the mechanisms of consolidation involved in the formation of MCC tablets, the first section deals with the basic mechanical properties of powders important for compression. Values of parameters describing ductility, brittleness, elasticity and viscoelasticity are presented and discussed in relation with the degree of polymerization, the crystallinity, the moisture content and the morphological properties of the materials.

The tableting properties of the powders during the compression process (densification behavior, work of compression) and the mechanical strength of the finished products (compactibility) are examined. Special attention is given to the effects of moisture content, lubricants and other added substances on the performances of MCC products. Comparative tablet weight variation data are provided for several MCC types from different supplies.

Finally, aging of the MCC compacts is discussed in relation to environmental conditions, before warning the user in the conclusion on the considerable variability of MCC products currently available on the market.     

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.     

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.     

Analysis of densification mechanisms of dry granulated materials

Dry granulation by roll compaction is a continuum manufacturing process to produce granules with improved flowability which can further be easily used in tableting process. However, the granules are non-homogeneous in density and have non-spherical shapes which impact their densification behaviour during die-compaction. The aim of this study was to investigate both the densification mechanism and the failure strength of granules of microcrystalline cellulose (MCC) and mannitol using Cooper-Eaton and Adams models. For both materials, the Cooper-Eaton approach led to the quantification of fractional volume compaction by particle rearrangement and by plastic deformation respectively to explain the difference in densification behaviour of raw material and granules. Moreover, the model showed its ability to capture the effect of granule density and granule sizes and to differentiate the densification mechanisms of MCC as a plastic material and mannitol as a brittle material. The Adams model was used to compute the failure strength of single granule from in-die compression data. The obtained results of the granules were in the range [0.6–1.43 MPa]. However, regarding the effect of granule density, the model showed mixed results indicating that the model is not representative of the studied granules which are not spherical and have a relatively wide range of sizes, nevertheless, the model was derived for near spherical particles with a narrow size distribution.     

Application of similarity factor in development of controlled-release diltiazem tablet

Controlled-release grade hydroxypropylmethylcellulose (HPMC) or xanthan gum (XG) and microcrystalline cellulose (MCC) were employed to prepare controlled-release diltiazem hydrochloride tablets. The similarity factor f₂ was used for dissolution profile comparison using Herbesser 90 SR as a reference product. Drug release could be sustained in a predictable manner by modifying the content of HPMC or XG. Moreover, the drug release profiles of tablets prepared using these matrix materials were not affected by pH and agitation rate. The f₂ values showed that only one batch of tablets (of diltiazem HCl, HPMC or XG, and MCC in proportions of 3.0:3.0:4.0) was considered similar to that of the reference product, with values above 50. The unbiased similarity factor f^*₂ values were not much different from the f₂ values, ascribing to a small dissolution variance of the test and reference products. The amount of HPMC or XG incorporated to produce tablets with the desired dissolution profile could be determined from the curves of f₂ versus polymer content. Hence, the f₂ values can be applied as screening and optimization tools during development of controlled-release preparations.     

Comparative evaluation of soy polysaccharide as direct compression excipient

Commercial soy polysaccharide (Emcosoy^R) has been evaluated as direct compression excipient in comparison with two frequently used materials, microcrystalline cellulose (Avicel pH 101) and pregelatinized maize starch (Sta-RX 1500).

Moisture sorption and desorption data analysed according to the Young and Nelson and the GAB equations and mechanical properties such as tensile strength, brittle fracture probensity, interparticle bonding isotropy and yield pressure of compacted excipients after storage at various environmental relative humidities are reported. Tableting characteristics such as punch force ratio, weight variation, tensile strength, friability, capping tendency, disintegration and dissolution of mixtures of the excipients and paracetamol are compared.

Emcosoy has been found to behave like Avicel as direct compression binder but like Sta-RX as disintegrant.     

Fluidity and tableting characteristics of a powder solid dispersion of the low melting drugs ketoprofen and ibuprofen with crospovidone

A powder solid dispersion system (SD) of ketoprofen (KP) or ibuprofen (IP), which possess low melting points, plus crospovidone (CrosPVP), have good fluidity characteristics and can be used to formulate tablets. Tablets of KP or IP in the SD of adequate hardness within a narrow weight range can be prepared by direct compression. Addition of microcrystalline cellulose (MCC) resulted in greater hardness characteristics and less variation in tablet weight. Forces during the tableting process were measured with a tableting process analyzer (TabAll) equipped with a single-punch for determining capping and sticking properties during the tableting process. Pressure transmission ratio from the upper to the lower punch and die wall force were increased by adding 1% magnesium stearate (MS) to the SD. Ejection force decreased when MS was added to the SD. When tablets of the IP SD were prepared without excipient, scraper pressure (SP) was large, resulting in sticking. However, addition of 1% MS, lowered the SP value and eliminated sticking. Thus, an SD of compounds with a low melting point such as KP or IP is suitable for tablet manufacture by direct compression with the addition of 1% MS.     

Evaluation of Era-Tab as a Direct Compression Excipient

The physical and compressional properties of a modified rice starch, Era-Tab, were evaluated and compared with those of 4 commercially available direct compression excipients, namely, microcrystalline cellulose (Avicel PH-101), partially pregelatinized starch, spray-dried lactose (Super-Tab Lactose), and granular dicalcium phosphate dihydrate (Emcompress). It was found that Era-Tab possessed high flowability and adequate compressibility. The compacted material made with Era-Tab has a higher crushing strength and a lower friability than 3 other direct compression excipients, except microcrystalline cellulose. Tablets containing terfenadine of the same degree of hardness (10 kg) were also prepared using different direct compression excipients. The disintegration time of the tablets made with Era-Tab was approximately 2.5 min. The maximum of the accumulated percentage of terfenadine released from the tablet reached 90%, and 63.2% of it was released within 20 min. Both the powder characteristics and tablet properties show that the modified rice starch, Era-Tab, is a useful product as a direct compression tablet excipient.     

Fluidity and Tableting Characteristics of a Powder Solid Dispersion of the Low Melting Drugs Ketoprofen and Ibuprofen with Crospovidone

ABSTRACT

A powder solid dispersion system (SD) of ketoprofen (KP) or ibuprofen (IP), which possess low melting points, plus crospovidone (CrosPVP), have good fluidity characteristics and can be used to formulate tablets. Tablets of KP or IP in the SD of adequate hardness within a narrow weight range can be prepared by direct compression. Addition of microcrystalline cellulose (MCC) resulted in greater hardness characteristics and less variation in tablet weight. Forces during the tableting process were measured with a tableting process analyzer (TabAll) equipped with a single-punch for determining capping and sticking properties during the tableting process. Pressure transmission ratio from the upper to the lower punch and die wall force were increased by adding 1% magnesium stearate (MS) to the SD. Ejection force decreased when MS was added to the SD. When tablets of the IP SD were prepared without excipient, scraper pressure (SP) was large, resulting in sticking. However, addition of 1% MS, lowered the SP value and eliminated sticking. Thus, an SD of compounds with a low melting point such as KP or IP is suitable for tablet manufacture by direct compression with the addition of 1% MS.     

Differentiation of the surface topographies of pharmaceutical excipient compacts

The comparison of conventional surface metrology and area-scale fractal parameters to differentiate the surface topography of pharmaceutical excipient compacts and preliminary investigation of scale-based correlations with excipient properties were performed. The determination and selection of the most appropriate surface topography parameters is important in optimizing the design and quality of industrial processes and products. The surfaces of three types of excipient compacts (microcrystalline cellulose (MCC), spray dried lactose (SDL), and dibasic calcium phosphate dihydrate (DCPD)) were characterized with a non-contact optical surface profilometer. A statistical F-test matrix was used to rank and quantify the ability of conventional surface texture parameters: Sa, Sq, St, Ssk, Sku, and the fractal parameters: relative area, Asfc (complexity) and SRC (smooth–rough crossover), to differentiate the surfaces of the compacts. Based on this statistical analysis and area-scale plots generated from profilometer data, it was found that most of the conventional parameters were suitable for distinguishing the surfaces. The F-test applied to the relative areas as a function of scale also indicated the ranges of scales over which the differentiation was possible. MCC–SDL and DCPD–SDL material pairs were able to be differentiated between scales of 10 and 10,000 μm², however, MCC–DCPD pairs were only differentiable between 300 and 2000 μm². A new method was established for illustrating the scale-based correlations, using the product of the regression coefficient and the normalized slope. The correlations between the fractal parameters and the properties of the excipients, including brittle fracture and indentation hardness, gave plausible explanations for the similarities between certain excipients, supporting a phenomenological understanding of the behavior of excipient compacts and their surfaces.     

Evaluation of non-crystalline cellulose as a novel excipient in solid dose products

Objective: The objective of this study was to evaluate non-crystalline cellulose (NCC) as a novel tablet excipient in solid oral dosage forms in comparison with microcrystalline cellulose (MCC) and silicified microcrystalline cellulose (Prosolv®, SMCC).

Significance: MCC, although a widely used tablet excipient, has diasdvantages in terms of its low dilution potential for potent drugs, and sensitivity to lubricant and moisture. SMCC, a modified version of MCC, has improved tablet compression properties. However, SMCC is expensive and also affects the moisture sorption and particle deformation during compression leading to increased tensile strength and tablet hardness. NCC was found to be similar to SMCC in its performance as a tablet excipient and thus can serve as a cheaper alternative to SMCC.

Methods: Scanning electron microscopy (SEM), X-ray diffrectometry (XRD), and differential scanning calorimetry (DSC) analyses were performed on NCC, MCC, and SMCC. Further, out-of-the die Heckel, Kawakita compact densification and stress-strain analyses were performed to evaluate their compaction and compressibility properties. Various compendial and non-compendial tests were performed to to determine the flow properties of materials. Dissolution studies were performed using amlodipine besylate as a marker drug.

Results: It was found that NCC has similar or even better flow properties and compactibility than MCC due to its porous and amorphous structure whereas it had similar properties as SMCC.

Conclusions: Based on the data, it can be concluded that NCC can serve as a cheaper and better alternative to MCC as excipient in solid dosage forms.     

纳米纤维素增强淀粉食品包装材料的研究进展

目的 为了解决纯淀粉材料力学性能低、脆性大等缺点,探索纳米纤维素对淀粉膜材料的影响,为食品包装材料领域和替代传统石油基的高分子材料方向提供新的思路。方法 通过跟进国内外纳米纤维增强淀粉相关研究和应用进展,概括3种纳米纤维素的性能,介绍淀粉食品包装材料未来将面临的挑战和机遇,重点分析纳米纤维素对淀粉膜性能的影响。结论 纤维素纳米纤维（CNF）、纤维素纳米晶（CNC）和微晶纤维素（MCC）对淀粉进行增强后,淀粉复合材料的力学性能、阻隔性能和热学性能均得到改善,纳米纤维素增强淀粉食品包装材料在未来食品包装领域将得到扩展。     

Comparative evaluation of soy polysaccharide as direct compression excipient

Abstract

Commercial soy polysaccharide (Emcosoy^R) has been evaluated as direct compression excipient in comparison with two frequently used materials, microcrystalline cellulose (Avicel pH 101) and pregelatinized maize starch (Sta-RX 1500).

Moisture sorption and desorption data analysed according to the Young and Nelson and the GAB equations and mechanical properties such as tensile strength, brittle fracture probensity, interparticle bonding isotropy and yield pressure of compacted excipients after storage at various environmental relative humidities are reported. Tableting characteristics such as punch force ratio, weight variation, tensile strength, friability, capping tendency, disintegration and dissolution of mixtures of the excipients and paracetamol are compared.

Emcosoy has been found to behave like Avicel as direct compression binder but like Sta-RX as disintegrant.     

Evaluation of Tablet Formation of Different Lactoses by 3D Modeling and Fractal Analysis

ABSTRACT

The aim of this study was to use 3D modeling to differentiate not only among the four different types of lactose α-lactose monohydrate, spray-dried lactose, agglomerated lactose and lactose anhydrous but also between products from different manufacturers. Further “box-counting” fractal analysis of SEM images was done to gain additional information on tableting characteristics and tablet properties which can be found in the fractal structure. Twelve different materials from different manufacturers were analyzed for their powder-technological and physicochemical properties. They were tableted on an eccentric tableting machine at graded maximum relative densities and the recorded data, namely force, time, and displacement were analyzed by the 3D modeling technique. Tablet properties such as, elastic recovery, crushing force and morphology were analyzed. The results show that 3D modeling can precisely distinguish deformation behavior for different types of lactose and also for the same type of material produced with a slightly different technique. Furthermore, the results showed that the amorphous content of the lactose determined the compactibility of the material, which is due to a reversible exceeding of the glass transition temperature of the material. The three fractal dimensions D_BW (box surface dimension), D_WBW (pore/void box mass dimension), and D_BBW (box solid mass dimension) are capable of describing morphological differences in lactose materials. Multivariate regression analysis showed that the fractal surface structure of the lactose-based materials is strongly correlated to tableting characteristics and tablet properties. Especially with regards to 3D modeling, it was found that the fractal indices can describe the parameters time plasticity d, pressure plasticity e, and fast elastic decompression, which is the inverse of ω. In addition, the 3D parameters are able to describe the powder and tablet fractal indices. In conclusion, the 3D modeling is not only able to characterize the compression process but it can also provide information on the final tablet morphology.