Abstract/Summary

Chapter 1 presents an introduction for crystal engineering in formulation development with emphasis on salt, co-crystal, and solid dispersion formation. Preparation, characterisation, and applications for oral and inhaled delivery are outlined, with a focus on preparation using spray drying. Chapter 2 reviews literature on solid dispersion formulations for carrier free, dry powder inhalation, outlining applications for antimicrobial and anticancer therapies. Chapter 3 reports four new ciprofloxacin salts with dicarboxylic acids and their X-ray, thermal, and spectroscopic characterisation. All salts showed enhanced saturated solubility, especially the glutaric acid salt which was higher than ciprofloxacin hydrochloride monohydrate. Chapter 4 describes the formulation of ciprofloxacin salt solid dispersions with HPMC, through contrasting three-fluid nozzle spray drying methods. The formulations showed modified ciprofloxacin release and enhanced powder aerosolisation properties. Solution and suspension spray drying methods generated solid dispersions with differing in vitro and in vivo drug release. Chapter 5 presents the preparation of spray dried progesterone formulations for dry powder inhalation. Form II progesterone polymorph was present in the crystalline state, independent of feedstock solvent or excipients. Formulations with HPMCAS showed no temperature induced phase change to Form I as well as increased kinetic solubility and fine particle fraction. Chapter 6 describes a new progesterone co-crystal following in silico and experimental screening, followed by provisional scale up method testing. The co-crystal showed enhanced dissolution compared to progesterone and then UtrogestranTM when formulated as a tablet. Chapter 7 explores how spray drying process parameters influence the preparation of salicylic acid:caffeine co-crystal. All two-fluid and three-fluid nozzle methods generated co-crytsal although to differing crystallinities and with additional crystalline caffeine phase dependent on feedstock composition. Chapter 8 summarises key findings with their critical evaluation and suggestions for future work. Spray drying can prepare salts, co-crystals, and solid dispersions for use in inhaled and oral formulation development.