Manipulation of carrier particles for inhalation
The work described in this thesis was performed to investigate the effect of altering the conditions of recrystallisation for selected sugars and sugar derivatives (lactose, trehalose dihydrate and trehalose octa-acetate (TOAc» in order to assess the physical effect on the material surface. In addition to recrystallised materials, amorphous materials were also produced. The short-acting betas- agonist, salbutamol sulphate, was subsequently used to assess the relative performance of these materials as drug carriers in a dry powder inhaler (OPI). The main aim of the research was to establish whether a relationship exists between the surface characteristics of a material and the performance of the material as a drug carrier in a OP!. A fundamental part of the research involved the physiochemical characterisation of the sugars, including solubility determinations for trehalose and TOAc in a range of ethanol:water solvents. Following recrystallisation, considerable time had to be spent in order to confirm the identity of the recrystallised TOAc material, as initial analysis was not conclusive in determining that the material had remained chemically unchanged following recrystallisation. Optimisation of drying of the TOAc material following recrystallisation was also performed, and X-ray crystallography of samples of the TOAc material suggested that it exists in at least three different crystalline forms. Characterisation of the surface roughness using laser profilometry was performed before the materials (sieved to obtain a particle size range of 63 - 90 J.U1l) were blended with salbutamol sulphate (micronised to a particle size of 5 J.U1l). A multi-stage liquid impinger (MSLI) was used to quantify in vitro the performance of each material as a drug carrier from the OPI device - FlowCaps® (Hovione). Overall, the results indicated that the surface roughness values (R.) required to achieve the optimum performance as a drug carrier were in the range of 1.9 to 2.7 J.U1l. Inaddition, when considering the hydrophilic or hydrophobic nature of the sugars assessed, a trend appeared to exist. The results indicated an optimum R. in the range of 1.9 to 2.3 J.U1l for materials that exhibited hydrophobic characteristics, and a range of 2.1 to 2.7 J..UD for materials that were considered hydrophilic. Inconclusion, the results obtained indicate that a relationship between the surface characteristics of a material and its performance as a drug carrier in a OPI does exist, but that the optimum relationship is determined by a number of factors. Inaddition to the surface characteristics, the physiochemical properties of the carrier material and the active drug together with the characteristics of the chosen OPI device itself, all contribute to the relationship that determines performance.