Bashaiwoldu, Abraham Bahre; (2002) Studies on the influence of composition and processing on the mechanical properties of pellets and compacted pellets. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

A study on the influence of formulation and processing factors on the mechanical properties of pellets produced by extrusion and spheronization has been conducted. Microcrystalline cellulose (MCC) was mixed with lactose or glyceryl monostearate (GMS) in different proportions. Similarly, mixtures of water with ethanol or glycerol were used as liquid binders. Based on the different rate of moisture removal, and means of heat and mass transfer, four different drying techniques namely: hot-air oven drying, freeze-drying, fluid-bed drying, as well as desiccation with silica-gel were used in the production of pellets. In addition, pellets containing model drug (paracetamol) and having different mechanical properties were prepared and coated with an aqueous dispersion of ethyl cellulose (Surelease®). A range of properties from a simple fracture load to detailed load/displacement curves were used to characterize the pellets in terms of their tensile strength, deformability, linear strain elastic modulus and shear strength. Additionally, dynamic mechanical analysis (DMA) established the viscoelastic properties of uncoated and coated pellets. A non-contact laser profilometer was also used to quantify the permanent structural change of the pellets after compaction. The Heckel plot, Kawakita compressibility constant, pressure/displacement and logarithm of pressure/density profiles were employed to study the compaction mechanism of the pellets. Compacted pellets were investigated in terms of their strength and volumetric elastic recovery. Statistical analysis established that freeze-drying, fluid-bed drying, and rapid evaporation of ethanol produced porous pellets which were weak, deformable, less strainable and resulted in rigid compacts. The strength and nonconnective nature of MCC was modulated by the incorporation of lactose, GMS, or glycerol. The brittle fracture, as indicated by Weibull modulus, of the lactose-rich pellets created new surfaces to form stronger compacts. Improvement in the deformability of the pellets with the addition of GMS, produced strong tablets with the lowest surface roughness. The increase in phase angle, determined by DMA, highlighted the increase in the viscous nature of the pellets as a result of coating.

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