Evaluation of AaltoCell as a filler for tablets compressed from high-shear wet granulated formulations
Abstract
Microcrystalline cellulose (MCC) is a purified, partially depolymerized cellulose, which is obtained by treating αcellulose 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 AaltoCell (TM) as an excipient in solid dosage forms.
The objective of this study was to evaluate the filler properties of three grades of AaltoCell (TM) to prepare paracetamol tablets with 50% (w/w) drug load and compare AaltoCell (TM) 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 AaltoCell (TM) A and Vivapur 101 formulations had the smallest particle size, whereas the AaltoCell (TM) 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 AaltoCell (TM) 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 AaltoCell (TM) 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 AaltoCell (TM) tablets was between 1-8.5 minutes. In addition, the AaltoCell (TM) tablets had fast dissolution with 78-84% of paracetamol released within 1 minute.
Overall, AaltoCell (TM) 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 AaltoCell (TM).
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Materials
Table 3. Formulations containing PVP used in pre-tests
Following excipients are mentioned in the study besides other: PVP (K30 BASF, Germany), Vivapur 101 (JRS Pharma, Germany, MCC), Starch 1500 (National Chemical, USA, corn starch), Aerosil 200 (Evonik Degussa Corp., Parsippany, USA, silica ), HPMC K100M (Dow Chemical Company, USA)
Source: Thuy Nguyen, Evaluation of AaltoCell (TM) as a filler for tablets compressed from high-shear wet granulated formulations, University of Helsinki, Faculty of Pharmacy, Division of Pharmaceutical Chemistry and Technology, May 2023