A study of the potential of spray drying for the production of respirable particles of protein drugs
The objective of this study was to determine whether spray drying is an appropriate method for the production of respirable particles of therapeutic proteins. Meeting this objective requires that active, stable, dry powders in the 1-5$\mu$m size range be obtained. A model protein, $\beta$-galactosidase, was used throughout the study.^ The first part of the experimental work focused on the effect of various processing and formulation variables on the critical quality attributes of the spray dried protein (residual activity, moisture content, particle size and yield). Statistically designed experiments were used so that both direct and interactive effects of the variables could be identified, and the most appropriate formulation and process established. In order to obtain acceptable product yields and moisture contents, relatively harsh drying conditions were required. This necessitated the inclusion of a stabilizer in the formulation to preserve enzyme activity. Trehalose was found to be the most suitable stabilizer of those evaluated (sucrose, mannitol, arginine hydrochloride and trehalose).^ Subsequent experiments were carried out to evaluate the in vitro deposition properties of the spray dried $\beta$-galactosidase from dry powder inhaler devices. Respirable fractions were determined using the twin impinger and cascade impactor. These in vitro devices divide the 'inspired' dose into different size fractions enabling the amount of material in the respirable size range to be calculated. The respirable fractions were comparable with published values for conventional small molecule drugs. The spray dried powders were found to be extremely sensitive to moisture with dramatic reductions in respirable fractions occurring after exposure of the powders to environments of high humidity.^ The respirable fractions were highly dependent on the inhaler device used, and the powder formulation. With less efficient inhaler devices, the presence of a coarser carrier material blended with the spray dried powder substantially improved the respirable fractions. The cascade impactor and twin impinger gave comparable estimates for respirable fractions and were both found to be suitable evaluation methods for dry powder inhalers. The merits of other size analysis methods in the testing of dry powders for inhalation were also evaluated. ^
Chemistry, Pharmaceutical|Health Sciences, Pharmacy
"A study of the potential of spray drying for the production of respirable particles of protein drugs"
Dissertations and Master's Theses (Campus Access).