Optimised crystal morphologies for active pharmaceutical ingredients and related studies

The majority of active pharmaceutical ingredients (APIs) are crystalline solids in their pure forms. Crystalline solids have definable morphologies, i.e. shape and size. Crystal morphology is determined by both the internal structure of the crystals and external factors during growth from solution. The morphology of a crystal batch can affect key processes during manufacturing. Companies generally accept whatever morphology the manufacturing process provides and deal with any subsequent problems by costly trouble‒shooting. Rational design of optimised morphologies for crystalline pharmaceutical solids would be a very significant technical and commercial advance. Chapter one introduces the concept of crystal nucleation and growth. The phenomenon of polymorphism alongside the causes and impact is discussed. A summary of the scope of instrumentation used in the investigation of crystal polymorphism and morphology, including crystal size distribution (CSD), is also included. Chapter two examines the research carried out during an exploration of the optimum crystallisation parameters of phenacetin. Following a morphological study, the impact this induces on particle density and flow properties is examined. The impact of impurities on the crystallisation properties of phenacetin is investigated. Significantly, the location of impurities within individual crystals is also studied. The third chapter describes an industrial collaboration looking at the resolution and polymorphic study of trometamol and lysine salts of ketoprofen and 2‒phenylpropionic acid (2‒PPA). Chapter four incorporates a solid state study on three separate compounds: 2‒chloro‒4‒nitroaniline, 4‒hydroxy‒N‒phenylbenzenesulfonamide and N‒acetyl‒D‒glucosamine‒6‒O‒sulfate. 2‒Chloro‒4‒nitroaniline and 4‒hydroxy‒N‒phenylbenzenesulfonamide both produced interesting, extreme morphologies which warranted further investigation as part of a collaborative study. Following a summarisation of results in chapter five, chapter six contains the full experimental details, incorporating spectral and other analytical data for all compounds synthesised during the course of the research.

Resigning: a classic grounded theory of working within constraints when caring for stroke patients in the acute general care setting

This research aims to explore the challenges nurses face, when caring for stroke patients on a general medical/surgical ward, in the acute care setting and identify how nurses resolve or process this challenge. Healthcare environments continue to face the pressures of constraints such as reduced staffing levels, budgets, resources and less time, which influence care provision. Patient safety is central in care provision where nurses face the challenge of delivering best quality care when working within constraints. The incidence of stroke is increasing worldwide and internationally stroke units are the recognised minimum standard of care. In Ireland with few designated stroke units in operation many stroke patients are cared for in the acute general care setting. A classic grounded theory methodology was utilised for this study. Data was collected and analysed simultaneously through coding, constant comparison, theoretical sampling and memoing. Individual unstructured interviews with thirty two nurses were carried out. Twenty hours of non-participant observations in the acute general care setting were undertaken. The main concern that emerged was working within constraints. This concern is processed by nurses through resigning which consists of three phases; idealistic striving, resourcing and care accommodation. Through the process of resigning nurses engage in an energy maintenance process enabling them to continue working within constraints. The generation of the theory of resigning explains how nurses’ resolve or process working within constraints. This theory adds to the body of knowledge on stroke care provision. This theory has the potential to enhance nursing care, minimise burnout and make better use of resources while advocating for best care of stroke patients.