Ultrasound-assisted surface engineering of pharmaceutical powders

Effective processing of powdered particles can facilitate powder handling and result in better drug product performance, which is of great importance in the pharmaceutical industry where the majority of active pharmaceutical ingredients (APIs) are delivered as solid dosage forms. The purpose of this work was to develop a new ultrasound-assisted method for particle surface modification and thin-coating of pharmaceutical powders. The ultrasound was used to produce an aqueous mist with or without a coating agent. By using the proposed technique, it was possible to decrease the interparticular interactions and improve rheological properties of poorly-flowing water-soluble powders by aqueous smoothing of the rough surfaces of irregular particles. In turn, hydrophilic polymer thin-coating of a hydrophobic substance diminished the triboelectrostatic charge transfer and improved the flowability of highly cohesive powder. To determine the coating efficiency of the technique, the bioactive molecule β-galactosidase was layered onto the surface of powdered lactose particles. Enzyme-treated materials were analysed by assaying the quantity of the reaction product generated during enzymatic cleavage of the milk sugar. A near-linear increase in the thickness of the drug layer was obtained during progressive treatment. Using the enzyme coating procedure, it was confirmed that the ultrasound-assisted technique is suitable for processing labile protein materials. In addition, this pre-treatment of milk sugar could be used to improve utilization of lactose-containing formulations for populations suffering from severe lactose intolerance. Furthermore, the applicability of the thin-coating technique for improving homogeneity of low-dose solid dosage forms was shown. The carrier particles coated with API gave rise to uniform distribution of the drug within the powder. The mixture remained homogeneous during further tabletting, whereas the reference physical powder mixture was subject to segregation. In conclusion, ultrasound-assisted surface engineering of pharmaceutical powders can be effective technology for improving formulation and performance of solid dosage forms such as dry powder inhalers (DPI) and direct compression products.

Disabled Revolutionary War Veterans and the Construction of Disability in the Early United States, c. 1776-1840

This thesis addresses the following broad research question: what did it mean to be a disabled Revolutionary War veteran in the early United States during the period from 1776 to roughly 1840? The study approaches the question from two angles: a state-centred one and an experiential one. In both cases, the theoretical framework employed comes from disability studies. Consequently, disability is regarded as a sociocultural phenomenon rather than a medical condition. The state-centred dimension of the study explores the meaning of disability and disabled veterans to the early American state through an examination of the major military pension laws of the period. An analysis of this legislation, particularly the invalid pension acts of 1793 and 1806, indicates that the early United States represents a key period in the development of the modern disability category. The experiential approach, in contrast, shifts the focus of attention away from the state towards the lived experiences of disabled veterans. It seeks to address the issue of whether or not the disabilities of disabled veterans had any significant material impact on their everyday lives. It does this through a comparison of the situation of 153 disabled veterans with that of an equivalent number of nondisabled veterans. The former group received invalid pensions while the latter did not. In comparing the material conditions of disabled and nondisabled veterans, a wide range of primary sources from military records to memoirs and letters are used. The most important sources in this regard are the pension application papers submitted by veterans in the early nineteenth century. These provide us with a unique insight into the everyday lives of veterans. Looking at the issue of experience through the window of the pension files reveals that there was not much difference in the broad contours of disabled and nondisabled veteran life. This finding has implications for the theorisation of disability that are highlighted and discussed in the thesis. The main themes covered in this study are: the wartime experiences of injured American soldiers, the military pension establishment of the early United States and the legal construction of disability, and the post-war working and family lives of disabled veterans. Keywords: disability, early America, veterans, military pensions, disabled people, Revolutionary War, United States, disability theory.