Investigating the mechanical properties of pharmaceutical excipients in granule and tablet production

Shinebaum, Rachael (2022). Investigating the mechanical properties of pharmaceutical excipients in granule and tablet production. University of Birmingham. Eng.D.

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Abstract

Pharmaceutical tablets are commonly used as they are inexpensive to produce and have high acceptability amongst patients. Tablets are often made by direct compression of a powder formulation and when this is not achievable, a granular intermediate is produced before the compression process. Granulation is especially advantageous in the presence of powder handling difficulties such as poor flow or dusting. However, granulation can lead to a reduction in tablet tensile strength which is to be avoided to ensure a high-quality product. The current study investigates twin screw wet granulation and the result of changing process parameters on the tabletability of a range of materials. Granules were characterised by shape, internal structure and porosity while a compression simulator was used to find differences in tabletability based on the excipient used and process parameters.

To develop an understanding of the bonding mechanisms within tablets a comprehensive and thorough study of tablet properties surrounding the moisture content of materials was carried out. Pharmaceutical excipients were chosen based on their mechanical properties and hygroscopicity then directly compressed to identify the difference in tabletability due to the powder characteristics. A distinct difference in the tablet compaction process was identified between excipients which undergo brittle fracture and those which exhibit plastic deformation. The resultant tablet strength of hygroscopic powders is different depending on the moisture content gained by storage in changing relative humidity. This not only highlights the potential changes in material structure bought about by water, but also the importance of the control of storage conditions of hygroscopic materials for industrial purposes.

To further understand the role water plays in tabletability, magnesium stearate was used as a lubricant in microcrystalline cellulose (MCC) tablets. MCC is known to be highly lubricant sensitive, meaning that a reduction in tablet tensile strength is observed with increasing magnesium stearate concentration. However, a lubricant such as magnesium stearate is often required in the pharmaceutical tableting process. This study presents a hypothesis as to why magnesium stearate presents such problems during formulation work and how these problems are exacerbated by the presence of increasing moisture. To confirm the hypothesis, Raman spectroscopy was employed to visualise the areas of high magnesium stearate concentration within a tablet.

Alongside the powder characteristics identified as important in the prediction of tabletability presented within this study, surface energy presents an additional area of investigation for future study. Mannitol derivatives with different surface energies were successfully used in a tabletability feasibility study to assess the importance of surface energy in isolation to other differences in powder properties.

Type of Work:

Thesis (Doctorates > Eng.D.)

Award Type:

Doctorates > Eng.D.

Supervisor(s):