Browsing by Subject "tensile strength"
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(2020)Granulation is used to improve the flowability of pharmaceutical powders, reduce the amount of fines and increase the density of the material. Roller compaction has shown growing interest in recent years and it is used ever more frequently in pharmaceutical industry. Roller compaction has many superior qualities compared to wet granulation such as good control of process and absence of moisture and heat in the process. It is also cost effective compared to traditional granulation methods. New APIs are often sensitive to moisture. Therefore traditional granulation methods cannot be used. In the roller compaction process powder mixture is fed between two counter-rotating rolls where the compaction occurs and ribbon is formed. After compaction the ribbon is crushed into granules of desired size. The aim of this study was to find out how the mixture ratio of plastic and brittle material affects the physical properties of roller compacted ribbons such as the strength and stiffness of the ribbons and the structure of the ribbon surface. The materials used were microcrystalline cellulose and dicalsiumphosphate. Nine powder mixtures of 0 to 40 w-% of dicalsiumphosphate were prepared after which the mixtures were roller compacted with the same compactor parameters. Two methods were developed to study the above mentioned characteristics of the ribbons. For the stiffness and strength studies a 3-point bending method was developed for Lloyd material tester. For the surface structure characteristics of ribbons a measurement set up for FlashSizer 3D image analysis device was designed. Bending tests for the ribbons were performed in two different directions. For each batch of ribbons a slope of the linear area and maximum point of bending curves were defined, which represent the stiffness and strength of the ribbons accordingly. Also Young’s modulus and tensile strength were calculated, which are characteristics of a given material. In addition area under curve, which represents the work done to break the ribbon, was calculated. The strength and stiffness of the ribbons decreased with the increasing amount of dicalsiumphosphate. A clear trend was observed. Also Young’s modulus, tensile strength and AUC decreased accordingly. The increase of dicalciumphosphate led to diminished compactibility of the powder mixtures. The compaction force was probably not high enough to fragment the dicalsiumphosphate particles. The ribbons showed higher strength and stiffness when the bending was done perpendicularly ie. across the ribbon width compared to parallel measurements. Also relative standard deviations were smaller in this measurement set up. The 3-point bending method could not mostly distinguish between adjacent formulations from each other but when the difference in the amount of dicalsiumphosphate increased to 10-20 w-% statistically significant differences were observed in most of the calculated values. The surface structure of the ribbons differed between formulations when evaluated visually. Ribbons with less dicalsiumphosphate had a surface structure that followed the knurled pattern of the compactor rolls better.
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(2017)Twin screw granulation (TSG) has gained considerable interest as a continuous wet granulation method in the pharmaceutical industry and has been studied the most. However, there is still lack of understanding how continuous granulation affects the material compaction behavior even though it has been noticed in several dry and batch wet granulation studies that the granulation process has an influence on the final tablet strength. Thus, studies on the material compactability and tabletability after continuous wet granulation are relevant for the overall understanding of twin screw granulation process and its effect on material behavior in tableting. Hence, the main objective of this study was to investigate the influence of continuous twin screw granulation on the compactability and tabletability of commonly used excipients. Additionally, the impact of binder on the compaction behavior of materials was examined. Furthermore, the suitability of two "loss in compressibility" models i.e. the Unified Compaction Curve (UCC) model and a porosity model to predict the loss in tablet strength after twin screw granulation and for the materials used was assessed. Earlier, the models have been applied to dry and batch wet granulations only. Full factorial design of three variables (binder type, binder addition method and the number of kneading elements) with two levels was conducted for the ConsiGma1 twin screw granulation of formulations containing microcrystalline cellulose (MCC), mannitol or anhydrous dicalcium phosphate (DCPA) as the main excipient and polyvinylpyrrolidone (PVP) or hydroxypropyl cellulose (HPC) as binder. Magnesium stearate was added as lubricant after granulation prior to tableting. In addition to the full factorial design, granulation with PVP, dry binder addition and four kneading elements was repeated for each main excipient. In total this made 27 experiments. The granules were dried and milled after granulation and all the batches were tableted. Additionally, all the formulations were direct compressed in order to be able to detect the change in compactability and tabletability after granulation. Torque of the granulation was determined as well as bulk density and particle size distribution of the granules. Additionally, the tensile strength and porosity of the tablets were analysed. Tabletability and compactability were determined based on the compaction pressure and the obtained tensile strength and porosity values of the tablets. Furthermore, parameters (PWG, TWG and εWG) describing the loss in compressibility models were calculated. MCC experienced loss in compactability and tabletability after twin screw granulation due to hornification effect. On the other hand, the compaction behavior of mannitol improved due to the formation of porous granules. The compactability of DCPA decreased and the tabletability increased. However, the change was only moderate presumably due to brittle nature of DCPA. Additionally, the binder type had an effect of the compaction behavior of the materials, PVP producing stronger tablets compared with the less hydrophilic HPC. However, the binder addition method played only a small role in modifying the compaction behavior. The UCC model was applicable to MCC as loss in tabletability was detected. Thus, the model can be used to predict tablet tensile strength when MCC is granulated with twin screw granulator. Additionally, the UCC model can be used to design the granulation process to achieve a target tensile strength based on small scale preliminary studies thus reducing the resources needed for case-studies. However, the UCC model was not feasible to mannitol and DCPA because they experienced improvement in tabletability after twin screw granulation. The porosity model was applicable to MCC and DCPA but not to mannitol as it showed improvement in compactability. The porosity model described the loss in compactability of MCC only moderately due to lack of tensile strength data points and the linearity of the tensile strength-porosity relationship. However, the model described well the loss in compactability of DCPA at tablet porosities achieved with compaction pressures used in industry. As a conclusion, the results demonstrate that twin screw granulation can have a significant impact on the final tablet strength and that the compaction behavior of the formulation can change either way depending on the used materials. Furthermore, the small influence of the binder addition method on the tablet strength indicates that the time consuming binder dissolving process step can be excluded from the tablet production chain enabling continuous manufacturing with twin screw granulation.
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