Browsing by Subject "high-shear wet granulation"
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(2023)Microcrystalline cellulose (MCC) is a purified, partially depolymerized cellulose, which is obtained by treating α-cellulose with mineral acids. Ever since the first microcrystalline cellulose was commercialized, different grades of microcrystalline cellulose have widely been used in the manufacture of solid dosage forms, such as tablets. MCC obtained from different sources will exhibit different physico-chemical properties, including moisture content, degree of polymerization, crystallinity, and particle morphology. In wet granulation, microcrystalline cellulose can be used as a filler, binder, and disintegrant. Recently, Aalto University has introduced a novel microcrystalline cellulose obtained from renewable raw materials by an integrated process, which has a short retention time, low energy and chemical consumption. However, very few studies have evaluated the use of AaltoCellTM as an excipient in solid dosage forms. The objective of this study was to evaluate the filler properties of three grades of AaltoCellTM to prepare paracetamol tablets with 50% (w/w) drug load and compare AaltoCellTM with a commercial microcrystalline cellulose, Vivapur 101. Due to the poor flowability of paracetamol and the experimental microcrystalline celluloses, it is challenging to direct compress tablets from paracetamol and microcrystalline mixtures. Thus, the powder mixtures were granulated by high-shear wet granulation method to improve the flowability. After the granulation, the formulations were characterized for particle size distribution, morphology and powder flow. Carr’s index Hausner ratio and angle of repose were calculated to evaluate the flowability of the formulations. In addition, an image-based analysis of powder flow was performed. A rotary tablet press equipped with single punches of 9 mm diameter was used to compress tablets. To evaluate the quality of tablets, European Pharmacopoeia tests of friability, disintegration, uniformity of mass, uniformity of content and dissolution were conducted. The AaltoCellTM A and Vivapur 101 formulations had the smallest particle size, whereas the AaltoCellTM B had the largest particle size. According to Carr’s index and Hausner ratio, the flowability of AaltoCellTM powders and Vivapur 101 varied from poor to very, very poor. After the granulation, the flowability of AaltoCellTM B and AaltoCellTM C were classified as good, while AaltoCellTM A and Vivapur 101 formulations had fair flowability. However, the results were conflicting with the flowability index values obtained in the image-based analysis. According to the results, the AaltoCellTM tablets complied with all criteria of European Pharmacopoeia and were comparable with Vivapur 101 tablets. The average tablet weight deviated ± 3.2% from the target weight. The variations in weight and drug content were small, as indicated by low RSD values. The disintegration time of the AaltoCellTM tablets was between 1-8.5 minutes. In addition, the AaltoCellTM tablets had fast dissolution with 78-84% of paracetamol released within 1 minute. Overall, AaltoCellTM is a promising excipient for use as a filler in tablets. In further studies, characterizing the powder properties, such as morphology, surface properties and hygroscopicity, would provide a better understanding of the properties of AaltoCellTM.
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(2021)Mini-tablets are 1-3 mm in diameter and administered as a single tablet or as a multi-particulate formulation. Mini-tablets are an attractive alternative for conventional solid dosage forms due to the ease of administration and the possibility for combination and individualised drug therapy. In mini-tablet production, good flowability of the formulation is critical as minor variations in die filling can lead to significant changes in mini-tablet weights. In addition, to reduce weight variation, the particle size should not exceed 1/3rd of the die diameter. This study aimed to determine the influence of the granule size on mini-tablet weight variability and content uniformity. The feasibility of direct compression, as well as high-shear wet granulated and roller-compacted formulations, were evaluated. From the nine final formulations manufactured, particle size distribution, Hausner ratio, Carr’s index, angle of repose and flowability were determined. The mini-tablets were made on a rotary tablet press using single punches of 3 mm in diameter. Content uniformity and weight variation of the mini-tablets were determined. The direct compression formulation had the smallest particle size, and the roller-compacted formulation milled through a 1.0 mm and 1.25 mm square screen had the largest particle size. Surprisingly, the RC 0.8 mm grater screen formulation had a very wide particle size distribution and is classified as a very fine blend. The wide particle size distribution might result from a high fill ratio during the milling of the roller-compacted ribbons. The four different high-shear wet granule formulations had a very similar particle size distribution. According to the Hausner ratio and Carr’s index values, the flow properties of the formulations varied between fair and very poor, while according to the angle of repose, the flow properties were between excellent and poor. However, all nine formulations were used to make mini-tablets with acceptable uniformity of mass, mini-tablets were within ± 8 % of the target weight, and none exceeded the 10 % limit set by Ph. Eur. The weight variation is small, as indicated by the low RSD of 1.0-2.9 %. The differences in the weight variation may be attributed to segregation due to particle or granule size and density. This is further supported by the fact that no force feeder or vacuum was utilised in the rotary tablet press, possibly causing re-circulation of the formulation and shearing forces. In addition, the fill level of the feeder might have varied between the nine formulations and affect the weight variation in a way that is not recognised in this study. Only direct compression formulation was within the limits of uniformity of content of single-dose preparations set by Ph. Eur. In the final formulations, the amount of paracetamol was in the HSWG 0.8 mm round screen 98.5 % and in the RC 1.0 mm square screen 97.7 %. These results suggest that the formulations contained an adequate amount of paracetamol, which does not explain why the mini-tablets made from high-shear wet granules did not meet the content uniformity criteria. Furthermore, the weight variation might not entirely explain why high-shear wet granulated formulations performed so poorly in the content uniformity analysis. In summary, that direct compression is a feasible manufacturing method for mini-tablets of 3 mm in diameter. However, further studies are needed on the content uniformity of mini-tablets made using high-shear wet granulated and roller-compacted formulations as these did not meet the content uniformity criterion. In particular, the content uniformity of the mini-tablets made from the high-shear wet granulated formulations was not acceptable, and the reason for this was not identified.
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