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Effect of excipient mixture ratio on the porosity of binary (♦) and bilayer (□) tablets compressed at 61.9 MPa Figures 2(b), 2(c), 2(d) and 2(e) show effect of compression pressure on the tensile strength of binary and bilayer tablets (50/50 excipient blend ratio) formulated with MCC/EC (plastically deforming materials), MCC/dextrate and MCC/ lactose (brittle fracture materials), respectively. There was no significant difference between the binary and bilayer tablets (p > 0.05) in the case of MCC/lactose (Fig 2(e).
Source publication
Purpose: To comparatively evaluate the tableting properties of binary mixtures and bilayer tablets containing plastic deformation and brittle fracture excipients. Methods: Binary mixture and bilayer tablets of microcrystalline cellulose (MCC), ethyl cellulose, anhydrous lactose and dextrate were prepared by direct compression and the effect of comp...
Contexts in source publication
Context 1
... was no significant difference between the binary and bilayer tablets (p > 0.05) in the case of MCC/lactose (Fig 2(e). Figure 3 shows the effect of excipient blend ratio on the porosity of binary and bilayer tablets compressed at 61.9 MPa. Particles below 200 µm showed less flowability, compared to larger particles. ...
Context 2
... consistent relationship was seen between tablet porosity and excipient blend ratio for both binary and bilayer tablets in all plots. Although there was a significant difference in porosity between binary and bilayer tablets at all excipient blend ratios, the porosity at 50/50 blend ratio for MCC/ethyl cellulose and dextrate/lactose was almost the same, as shown in Figure 3(a) and (d). ...
Context 3
... particles of each powder material might have rearranged themselves in the die leading to a closer packing structure, thus minimizing the porosity of its powder bed and hence, a coherent compact when compressed at increasing pressure. In Figure 3, no constant relationship was seen between the porosity of the tablet and the composition of both binary mixtures and bilayer tablets. ...
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Lactose is a very important pharmaceutical excipient used in tablet and inhalation products. It is prone to forming amorphous regions on processing however, and it can be problematical to characterize amorphic material in a sample. Differential Mechanical Analysis (DMA) with material pocket is a method which can be used to accurately determine very...
Citations
... Mechanical strength is an essential parameter that represents inter-particulate bonding. For tablet dosage form, it is recommended to determine the dominant ingredient's mechanical properties to predict the tablet's overall compressional behavior (Amin et al., 2012). One of the mechanical strengths is the compaction ability test. ...
The use of partially pregelatinized starch in tablet formulations is entirely various; one of them is disintegrant. Present pregelatinized starch is imported from another country, which is relatively expensive. In contrast, many plants can be used as starch sources, including cassava which is relatively abundant in Indonesia. This study aimed to determine the effect of using partially pregelatinized starch from cassava as a disintegrant in paracetamol tablets. In this study, seven formulas were used with different disintegrants, three formulas using partially pregelatinized starch from cassava with concentrations of F1 5%, F2 10%, and F3 15%, three formulas using Starch 1500 with the same concentration as partially pregelatinized starch from cassava and one control formula without disintegrant. The tablet was made using the wet granulation method. The tablets produced were tested for physical properties (hardness, disintegration, and dissolution). In addition, compact ability of partially pregelatinized starch from cassava was compared with Avicel, Starch 1500, and cassava starch. Based on the results of the study showed that partially pregelatinized starch from cassava produced tablets that tended to be capping with less hardness than tablets with Starch 1500 and control tablets. The compact ability test results showed that the compact ability of partially pregelatinized starch from cassava was better than Starch 1500 and cassava starch. The disintegration test results showed that tablets with partially pregelatinized starch from cassava had faster disintegration than tablets with Starch 1500 and control tablets. The dissolution profile of tablets with partially pregelatinized starch from cassava is also better than other formulas.
... This process compacts a material by releasing trapped air and reducing the gaps between particles, which improves the material's properties. Tensile strength can be improved by the application of compressive force in forming pharmaceutical tablets [21][22][23]. Increasing the compaction pressure has also improved the mechanical properties of maize residue pellets [24] and biomass grass pellets [25]. To date, limited literature is available that investigates the effect of compression on the tensile strength of discarded textile and paper waste pulp formed into sheets. ...
... The results suggest that for all the substrates tested, the tensile strength improves at a compressive load of 500 N as compared to 200 N. Figure 3b shows the percentage increase in tensile strength from 200 N to 500 N compressive load. The increased compressive load applied to the substrate causes the particles to rearrange, forming a tighter packed structure that minimizes porosity and enhances the tensile strength of the formed sheet [22]. The treatment at 5% NaOH caused the highest increase in tensile strength of 42% in newspaper substrate, followed by cotton and polycotton of 37% and 25%, respectively, while, for corrugated cardboard, the 500 N compressive load was also superior to 200 N, obtaining an optimum tensile strength increase of 12% for untreated sheets. ...
This study investigates the efficacy of using discarded textile (cotton and polycotton) and paper waste (newspaper and corrugated cardboard) as substrates to form sheets with optimum tensile strength. The effect of alkali treatment (sodium hydroxide (NaOH) and sodium bicarbonate (NaHCO3)), compressive loads (200 N and 500 N), and the use of binding agents (blackstrap molasses, sodium alginate, and cornstarch) were studied to optimize the tensile strength of homogeneous sheets. The alkali treatment using 5% NaOH for 5 h of soaking demonstrated the highest increase in tensile strength of 21% and 19% for cotton and newspaper, respectively. Increasing compressive load from 200 N to 500 N showed the highest increase in tensile strength of 37% and 42% for cotton and newspaper, respectively. Remarkably, among the binders, cornstarch at 20% concentration obtained an increase in tensile strength of 395%, 320%, 310%, and 185% for cotton, polycotton, corrugated cardboard, and newspaper sheets, respectively. The optimum results obtained from this study will be utilized to develop biodegradable seedling pots using discarded textile and paper waste.
... Mechanical strength is another important parameter that also represents the inter-particulate bonding. For tablet dosage form it is recommended to determine the mechanical properties of dominant ingredient so as to predict the overall compressional behavior of tablets [32]. Mechanical properties were estimated by measuring the tensile strength which was in the range of 0.932± 0.239-1.468 ...
... It was reported that D O values for different aceclofenac formulations were increased as the concentration of binder was increased. This phenomenon indicates that at die filling the initial packing of the formulations increases with the higher concentration of binder [32]. In formulations FC, FD, FE and FF, the amount of avicel PH 102 was high (27.5-35%) ...
... which resulted in increased hardness, tensile strength and less percentage friability (Table 3). Scientists also found that compaction behavior of powder bed mostly dependent upon the deformation properties of the blends and the applied processing methods [32]. ...
The objective of this study was based on the formulation development of fast dispersible Aceclofenac tablets (100 mg) and to evaluate the influence of pharmaceutical mixtures of directly compressible Avicel PH102 with Mannitol and Ac-di-sol on the compressional, mechanical characteristics and drug release properties. Fast dispersible Aceclofenac formulations were developed by central composite design (CCD). Among them the best possible formulation was selected on the basis of micromeritic properties, appropriate tablet weight and disintegration time for further study. Tablets were directly compressed using manual hydraulic press with a compressional force ranging from 7.2 to 77.2 MN/m². Pre and post compression studies were performed and the compressed formulations (FA-FF) were assessed for different quality tests. The Heckel and Kawakita equations were applied for determination of compressional behavior of formulations. The quality attributes suggested that formulation (FB) containing avicel PH 102 (20%), mannitol (25%) and ac-di-sol (3%) as best optimized formulation showing better mechanical strength i.e. hardness 35.40 ± 6.93N, tensile strength 0.963 MN/m², and friability 0.68%. Furthermore, compressional analysis of FB showed lowest PY value 59.520 MN/m² and Pk value 1.040 MN/m² indicating plasticity of the material. Formulation FB disintegrated rapidly within 21 seconds and released 99.92% drug after 45 min in phosphate buffer pH 6.8. Results of drug release kinetics showed that all formulations followed Weibull and First-order models in three different dissolution media. Avicel PH102 based formulation mixture exhibit excellent compactional strength with rapid disintegration and quick drug release.
... FF<FE<FC<FD<FA<FB. Formulation FG and FH were found to be outliers Amin and colleagues (23). ...
... FE<FF<FC<FD<FA<FB.Amin et al., 2012 stated that each powder has its own compressional characteristics. In the form of powder blend these characteristics get significantly changed which affects the tablet stability Amin and colleagues(23). ...
... FE<FF<FC<FD<FA<FB.Amin et al., 2012 stated that each powder has its own compressional characteristics. In the form of powder blend these characteristics get significantly changed which affects the tablet stability Amin and colleagues(23). Formulations FG and FH were found to be outliers for D A values which could be due to formualtion blend. It was observed that all formulations yielded low values of D o than D B due to particles fragmentation and particles rearrangement in the die at reduced pressure. ...
Objective of this study was based on the formulation development of fast dispersible Aceclofenac tablets (100mg) and to evaluate the influence of pharmaceutical mixtures of directly compressible Avicel PH102 with Mannitol and Acdisol on the compressional, mechanical characteristics and drug release properties. Fifteen different aceclofenac formulations were developed by central composite rotatable design (CCRD). Among them best possible formulations (FA–FH) were selected on the basis of micromeritic properties, appropriate tablet weight and disintegration time for further study. Tablets were compressed by direct compression method using hand held hydraulic press with a compressional force ranging from 8 to 80 MN/m 2 (MPa). Pre and post compression studies were performed and the compressed formulations (FA-FH) were assessed for different quality tests. The Heckel and Kawakita equations were applied for determination of compressional behavior of formulations. The quality attributes suggested that formulation (FB) containing avicel PH 102 (20%), mannitol (25%) and ac-di-sol (3%) as best optimized formulation showing better mechanical strength i.e. hardness 37.75 ± 0.14N, tensile strength 5.67MN/m 2 and friability 0.34%. Furthermore, compressional analysis of FB showed lowest P Y value 59.52 MN/m 2 and P k value 1.040 MN/m indicating plasticity of the material. Formulation FB disintegrated rapidly within 21 seconds and released 99.92 % drug after 45min in phosphate buffer pH 6.8. Results of drug release kinetics showed that formulations FA-FH followed Weibull and First-order models in three different dissolution media. Avicel based formulation mixture exhibit excellent compactional strength with rapid disintegration and drug release.
... Previous research on the bilayer tablet has focused on exploring 1) factors that can affect IBS, such as compaction pressure and material properties (6), punch curvature (7,8), and particle size (9), 2) test methods to determine IBS, such as tensile test, (10)(11)(12)(13) shear test (14), diametrical compression test (15)(16)(17)(18), three point bending test (19)(20)(21)(22), wedging test (8,23), and 3) comparison of different methods (24,25). However, in absence of an acceptance criterion, a specified value of the IBS is insufficient for judging whether or not the integrity of a bilayer tablet can be sustained during the downstream manufacturing processes, such as handling, coating, packaging, and shipping. ...
Purpose
To identify the minimum interfacial bonding strength (IBS) required for bilayer tablets to sustain the stresses experienced during manufacturing, transportation, and handling.
Methods
Bilayer tablets of a number of formulations with systematically varied IBS were prepared on a materials testing macine. Five bilayer tablets with the same IBS were repeatedly dropped at a fixed height in a friabilator and integrity of the interface was periodically examined. The number of tablets free from observable defects at the interface was plotted as a function of the number of drops. The IBS for all five tablets to remain intact after 1000 drops was taken as the minimum IBS for a given formulation.
Results
The minimum IBS depends on both layer composition and tablet size. For bilayer tablets made with more brittle materials or a larger size, a higher minimum IBS is required to pass the survival test. The incorporation of HPMC leads to a lower minimum IBS. An IBS of 0.26 MPa is sufficient for all bilayer tablet formulations and sizes to pass the survival test in this work.
Conclusions
A minimum IBS of 0.26 MPa is recommended as a tentative criterion for bilayer tablets of most materials to avoid quality issues arising from inadequate IBS.
... Emdex is a dextrate-based co-processed excipients which compresses by plastic deformation mechanism with low elastic energy, demonstrating excellent tabletability [24,26]. Formulations containing Prosolv ODT, MicroceLac, F-Melt Type C and Type M and CombiLac contain a combination of plastic (MCC) and brittle (lactose or mannitol) deforming materials which explains their good tabletability [27,28]. ...
... Formulations containing Prosolv ODT, MicroceLac, F-Melt Type C and Type M and CombiLac contain a combination of plastic (MCC) and brittle (lactose or mannitol) deforming materials which explains their good tabletability [27,28]. Similarly, Pharmaburst 500 and Compressol SM contain sorbitol which will provide good compression through plastic deformation and high mannitol content which will allow consolidation through brittle fragmentation [24,29]; the inclusion of silicon dioxide is thought to offset the hygroscopic nature of sorbitol in these co-processed excipients [30]. Ludiflash and SmartEx QD100 primarily contain mannitol which can be expected to provide brittle fragmentation under compaction leading to friable, weaker tablets compared to plastic excipients such as Avicel PH102 and Emdex [31,32]. ...
Co-processed excipients may enhance functionality and reduce drawbacks of traditional excipients for the manufacture of tablets on a commercial scale. The following study aimed to characterise a range of co-processed excipients that may prove suitable for dispersible tablet formulations prepared by direct compression. Co-processed excipients were lubricated and compressed into 10.5-mm convex tablets using a Phoenix compaction simulator. Compression profiles were generated by varying the compression force applied to the formulation and the prepared tablets were characterised for hardness, friability, disintegration and fineness of dispersion. Our data indicates that CombiLac, F-Melt type C and SmartEx QD100 were the top 3 most suitable out of 16 co-processed excipients under the conditions evaluated. They exhibited good flow properties (Carr’s index ˂ 20), excellent tabletability (tensile strength > 3.0 MPa at 0.85 solid fraction), very low friability (< 1% after 15 min), rapid disintegration times (27–49 s) and produced dispersions of ideal fineness (< 250 μm). Other co-processed excipients (including F-Melt type M, Ludiflash, MicroceLac, Pharmaburst 500 and Avicel HFE-102) may be appropriate for dispersible tablets produced by direct compression providing the identified disintegration and dispersion risks were mitigated prior to commercialisation. This indicates that robust dispersible tablets which disintegrate rapidly could be manufactured from a range of co-processed excipients.
... Data generated from tapped/bulk density is presented in Figure 5. Out of all the excipients tested, Emdex showed the best flow with a Carr's index of 11 %; this can be explained by its non-hygroscopic, uniform porous spheres (Amin et al., 2012;Bolhuis et al., 1985). ...
... Avicel HFE-102 is a mixture of 90% MCC and 10% mannitol produced by spray drying (Rojas et al., 2012); its compression profile highly resembled that of Avicel PH-102, which could be expected due to high concentration of MCC in both products (Thoorens et al., 2014). Emdex is a dextrose-based co-processed excipients which compresses by plastic deformation mechanism with low elastic energy, demonstrating excellent compression properties (Amin et al., 2012;Olmo and Ghaly, 1999). deforming materials which explains their good compressibility (Gharaibeh and Aburub, 2013;Hentzschel et al., 2012). ...
... deforming materials which explains their good compressibility (Gharaibeh and Aburub, 2013;Hentzschel et al., 2012). Similarly, Pharmaburst 500 and Compressol SM contain sorbitol which will provide good compressibility through plastic deformation and high mannitol content which will allow consolidation through brittle fragmentation (Amin et al., 2012;Rojas et al., 2013); the inclusion of silicon dioxide is thought to offset the hygroscopic nature of sorbitol in these co-processed excipients (Çelik, 2011). Ludiflash and SmartEx QD100 primarily contain mannitol which can be expected to provide brittle fragmentation under compaction leading to weak tablets (Al-Ibraheemi et al., 2013;Koner et al., 2015). ...
A medicine will not elicit its desired therapeutic effect if the patient is not able or willing to take it. The specific needs of the target population must be taken into account in the design of medicines. Evaluation of the effect of formulation factors on patient’s acceptability could guide the development of better medicines for children. Flexible solid oral dosage forms, including multiparticulates and (oro)dispersible formulations, offer advantages over conventional solid and liquid dosage forms to meet the needs of paediatric patients. These advantages include favourable stability profile, suitability for taste masking, flexibility of dose titration and convenient administration. The overall aims of this research were to identify barriers for the development of acceptable medicines for children, to explore methodology for palatability and patient’s acceptability testing and to generate evidence of acceptability of flexible solid oral dosage forms. Methodological tools for the assessment of palatability and acceptability were developed and the use of such tools was explored through a series of investigations in healthy volunteers using model placebo formulations. Pharmaceutical formulation work was performed to optimise formulation design and choice of excipients, integrating manufacturability and patient’s acceptability criteria. A direct comparison between palatability and acceptability outcomes in children and adults was performed, which highlighted the value of conducting studies in adults to provide initial guidance on formulation design. Some of the key formulation factors that affect acceptability of flexible solid oral dosage forms were identified, which can be used to guide the development of more palatable and acceptable medicines. This research also evidenced methodological barriers in the assessment of palatability and patient’s acceptability which are thoroughly discussed in this thesis and will need to be overcome in the future. The knowledge generated by this research is applicable not only to the development of medicines for children, but also for other subsets of the population.
... Several methods have been developed to quantify the strength of bilayer tablets, such as tensile test (Akseli et al., 2013;Anuar and Briscoe, 2010;Inman et al., 2007;Kottala et al., 2012a,b), shear test (Klinzing and Zavaliangos, 2013), diametrical compression test (Amin et al., 2012;Niwa et al., 2013;Papós et al., 2015;Wu and Seville, 2009), three point bending test (Busignies et al., 2013;Podczeck, 2011;Podczeck and Al-Muti, 2010;Podczeck et al., 2006), and V-shape punch breaking test (Busignies et al., 2014). Among these, the shear and tensile methods are, by far, the most commonly used for quantifying IBS of bilayer tablets. ...
Both shear and tensile measurement methods have been used to quantify interfacial bonding strength of bilayer tablets. The shear method is more convenient to perform, but reproducible strength data requires careful control of the placement of tablet and contact point for shear force application. Moreover, data obtained from the shear method depend on the orientation of the bilayer tablet. Although more time-consuming to perform, the tensile method yields data that are straightforward to interpret. Thus, the tensile method is preferred in fundamental bilayer tableting research to minimize ambiguity in data interpretation. Using both shear and tensile methods, we measured the mechanical strength of bilayer tablets made of several different layer combinations of lactose and microcrystalline cellulose. We observed a good correlation between strength obtained by the tensile method and carefully conducted shear method. This suggests that the shear method may be used for routine quality test of bilayer tablets during manufacturing because of its speed and convenience, provided a protocol for careful control of the placement of the tablet interface, tablet orientation, and blade is implemented.
... Normally, a tablet contains a combination of two or more powders to obtain a compact with the desired properties. Direct compression is still the method of choice for the manufacture of tablets where the components are mixed together before they are compressed directly into tablets (2,5). Rosuvastatin is an antilipidemic agent that competitively inhibits hydroxymethylglutarylcoenzyme A (HMG-CoA) reductase. ...
The aim was to design bilayer tablets of rosuvastatin and diltiazem hydrochloride to give conventional release of rosuvastatin calcium and sustained release of diltiazem hydrochloride. The conventional release layer comprised lactose and micro crystalline cellulose as diluents (separately and in combined form) and the sustained release layer comprised HPMC K100M and ethyl cellulose (with different ratio of HPMC K100M and ethyl cellulose) as the release retarding polymers. Direct compression method was used for formulation of the bilayer tablets. Preformulation studies were performed prior to compression. The bilayer tablets were evaluated for weight variation, dimension, hardness, friability, drug content, and disintegration time and in vitro drug release using USP dissolution apparatus type II (paddle). More than 90% of rosuvastatin calcium was released within 150 min. HPMC K100M and Ethyl cellulose sustained the release of diltiazem hydrochloride from the sustained release layer for 24 hour. After stability tests, degradation of both drugs were found but the drugs contents were found within the range. The release of diltiazem hydrochloride was found to follow a mixed pattern of Korsmeyer-Peppas, Higuchi model and zero order release models and the kinetic studies of the formulations revealed that diffusion is the predominant mechanism of drug release. The IR spectrum studies revealed that there was no disturbance in the principal peaks of pure drugs. This further confirms the integrity of pure drugs and no incompatibility of them with excipients. The stability studies were carried out for the optimized batch for three months and it showed acceptable results.
... Many researchers have attempted to study the compaction behavior and compressibility of binary mixtures of some pharmaceutical excipients during compression [19,[32][33][34][35][36]. For instance, Busignies et al. [34] observed that the specific compaction energy was proportional to the mixture composition expressed in mass, but this was not the case for the specific expansion energy. ...
The physical properties of pharmaceutical powders/granules are very important in the development of oral solid dosage forms. The aim of this paper was, in a first stage, to carry out an evaluation of the flow properties (angle of repose, flow time, compaction capacity, compressibility index, Carr index and Hausner ratio) of technological or primary excipients of tablets (microcrystalline cellulose and dibasic calcium phosphate dihydrate) which behave differently during compaction, either pure and in binary mixtures, whose composition varied between 20% (w/w) and 80% (w/w) at intervals of 20% (w/w). In a second stage, using an instrumented eccentric tableting machine, energies and exerted forces during compaction of these materials were measured and the compressibility curves were registered. In addition, plasticity index and lubrication coefficient were calculated and weight uniformity, thickness, hardness and tensile strength of the manufactured tablets were also evaluated. The obtained results demonstrated that the binary mixtures and the pure excipients showed similar flow properties. On the other hand, the obtained tablets with the plastic excipient had lower values of exerted force by the upper punch and apparent net energy, and higher values of plasticity index and time periods of the force/time compression profiles.
