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| 2. |
- Dumarey, Melanie, 1982-, et al.
(author)
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Combining experimental design and orthogonal projections to latent structures to study the influence of microcrystalline cellulose properties on roll compaction
- 2011
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In: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 416:1, s. 110-119
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Journal article (peer-reviewed)abstract
- Roll compaction is gaining importance in pharmaceutical industry for the dry granulation of heat or moisture sensitive powder blends with poor flowing properties prior to tabletting. We studied the influence of microcrystalline cellulose (MCC) properties on the roll compaction process and the consecutive steps in tablet manufacturing. Four dissimilar MCC grades, selected by subjecting their physical characteristics to principal components analysis, and three speed ratios, i.e. the ratio of the feed screw speed and the roll speed of the roll compactor, were included in a full factorial design. Orthogonal projection to latent structures was then used to model the properties of the resulting roll compacted products (ribbons, granules and tablets) as a function of the physical MCC properties and the speed ratio. This modified version of partial least squares regression separates variation in the design correlated to the considered response from the variation orthogonal to that response. The contributions of the MCC properties and the speed ratio to the predictive and orthogonal components of the models were used to evaluate the effect of the design variation. The models indicated that several MCC properties, e.g. bulk density and compressibility, affected all granule and tablet properties, but only one studied ribbon property: porosity. After roll compaction, Ceolus KG 1000 resulted in tablets with obvious higher tensile strength and lower disintegration time compared to the other MCC grades. This study confirmed that the particle size increase caused by roll compaction is highly responsible for the tensile strength decrease of the tablets.
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| 3. |
- Souihi, Nabil, et al.
(author)
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A Quality by Design approach to investigate the effect of mannitol and dicalcium phosphate qualities on roll compaction
- 2013
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In: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 447:1-2, s. 47-61
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Journal article (peer-reviewed)abstract
- Roll compaction is a continuous process for solid dosage form manufacturing increasingly popular within pharmaceutical industry. Although roll compaction has become an established technique for dry granulation, the influence of material properties is still not fully understood. In this study, a quality by design (QbD) approach was utilized, not only to understand the influence of different qualities of mannitol and dicalcium phosphate (DCP), but also to predict critical quality attributes of the drug product based solely on the material properties of that filler. By describing each filler quality in terms of several representative physical properties, orthogonal projections to latent structures (OPLS) was used to understand and predict how those properties affected drug product intermediates as well as critical quality attributes of the final drug product. These models were then validated by predicting product attributes for filler qualities not used in the model construction. The results of this study confirmed that the tensile strength reduction, known to affect plastic materials when roll compacted, is not prominent when using brittle materials. Some qualities of these fillers actually demonstrated improved compactability following roll compaction. While direct compression qualities are frequently used for roll compacted drug products because of their excellent flowability and good compaction properties, this study revealed that granules from these qualities were more poor flowing than the corresponding powder blends, which was not seen for granules from traditional qualities. The QbD approach used in this study could be extended beyond fillers. Thus any new compound/ingredient would first be characterized and then suitable formulation characteristics could be determined in silico, without running any additional experiments.
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| 4. |
- Souihi, Nabil, et al.
(author)
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Roll compaction process modeling : transfer between equipment and impact of process parameters
- 2015
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In: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 484:1-2, s. 192-206
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Journal article (peer-reviewed)abstract
- In this study the roll compaction of an intermediate drug load formulation was performed using horizontally and vertically force fed roll compactors. The horizontally fed roll compactor was equipped with an instrumented roll technology allowing the direct measurement of normal stress at the roll surface, while the vertically fed roll compactor was equipped with a force gauge between the roll axes. Furthermore, characterization of ribbons, granules and tablets was also performed. Ribbon porosity was primarily found to be a function of normal stress, exhibiting a quadratic relationship thereof. A similar quadratic relationship was also observed between roll force and ribbon porosity of the vertically fed roll compactor. The predicted peak pressure (Pmax) using the Johanson model was found to be higher than the measured normal stress, however, the predicted Pmax correlated well with the ribbon relative density/porosity and the majority of downstream properties of granules and tablets, demonstrating its use as a scale-independent parameter. A latent variable model was developed for both the horizontal and vertical fed roll compactors to express ribbon porosity as a function of geometric and process parameters. The model validation, performed with new data, resulted in overall good predictions. This study successfully demonstrated the scale up/transfer between two different roll compactors and revealed that the combined use of design of experiments, latent variable models and in silico predictions result in better understanding of the critical process parameters in roll compaction.
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| 5. |
- Svensson, Olof, et al.
(author)
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An evaluation of 2D-wavelet filters for estimation of differences in textures of pharmaceutical tablets
- 2006
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In: Chemometrics and Intelligent Laboratory Systems. - : Elsevier BV. - 0169-7439 .- 1873-3239. ; 84:1-2, s. 3-8
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Journal article (peer-reviewed)abstract
- In chemical imaging spectra are acquired over a surface with one spectrum for each pixel of the image. The obtained spectra usually carry a mixture of chemical and physical information. One may view the properties that vary over the image, the mean spectral magnitude from separate wavelength intervals, or better, PCA scores may be shown as images.In this way a multitude of images are compressed to a few images that in the PCA case are representative for the main variation in the sample images. These images may be viewed manually and deductions as to e.g. differences in homogeneity can be made. At an increased rate of samples, the observer will have difficulties coping with the repetitive work and different observers will most likely have slightly different interpretations. In order to automate the process of estimation of e.g. homogeneity and particle density, image filters can be used to calculate a small set of texture descriptors for each image. Calculations based on the 2D versions of the discrete wavelet transform (DWT) using Daubechies 14 and the dual tree complex wavelet transform (DT-CWT) using near-symmetric 13, 19 tap filters in combination with q-shift 14, 14 tap filters were evaluated for this purpose.The aim with this work is to evaluate texture descriptors based on a combination of 2D-wavelet filters and energy, i.e. l(1)-norm, calculations for each wavelet scale. These descriptors are then used as observations for overview in e.g. PCA. In this way the texture differences can be ranked by ordinary use of PCA or PLS.This method is tested on multivariate near infrared images of pharmaceutical tablets. Score images are selected to represent variations of the aggregate density and sizes in the compressed tablets. Images are shifted and rotated to compare shift and rotational independence of the texture descriptors.
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