Catherine.Ann Malton, Nottingham 1984
Well out of date but quite interesting if you are into inhalaled pharmaceutical dosage forms or aerosols. Most use now is to provide the odd supporting reference for any papers on similar formulation studies. If you are that far in you might be using some of her journal references anyway. There is a whole section on gamma camera work and all the animals were as happy and healthy after their experience as they were before.
The title is Biopharmaceutical Studies of Inhalation Aerosols by C. A. Malton
All about technicium generators and gamma camera studies on inhalation profiles and particle size. Note:- The links are all to pdfs that have not been OCR'd so you'll need to do that yourself if you want!Enjoy.
ABSTRACT
<p>Two concious animal models ( the rabbit and the beagle dog) have been
established
for the inhalation of therapeutic aerosols. The in-vivo aerosol deposition pattern
was measured using a gamma camera, allowing repeated evaluation with different
formulations in the same subject. Concious animals were used to avoid anaesthetic
effects on respiration and to allow dosing with materials which were not fully
tested toxicollogically for human use. Techniques were investigated for gamm
radiolabelling therapeutic aerosols containing salbutamol with technicium-99m
and two methods used for radiolabelling nebulised and metered dose aerosols.
The aerosols were administered via oral delivery devices designed to bypass
filtration by the nasal passages. The design of the administration chamber for
dogs also allowed co-ordination of firing a metered-dose inhaler with inspiration.
Metered-dose inhalers containing salbutamol with different activity median diameters
were administered to the dogs, and the gamma camera lung image showed differentiation
according to the particle size range of the aerosol, both in terms of total
dose delivered to the lung and activity distribution within the lung.</p>
<p>The mass and activity aerodynamic size distributions of the drug and
radionuclide
in the aerosol were simultaneously measured by an eight stage cascade impactor,
the Andersen Sampler. The dose fraction deposited in the administration chamber
in vivo was related to the fraction deposited in the glass 'throat' inlet to
the impactor. The Andersen Sampler was also used to measure the aerodynamic
size distributions of salbutamol and the surfactant (oleic acid), in a Ventolin
Inhaler. The results showed that the mass size distribution of oleic acid droplets
was finer than that of the drug particles.</p>
<p>Mean aerodynamic diameters of aerosols measured by the Andersen Sampler
were
related to projected area diameters from a laser light scattering instrument,
the PMS-CSASP-100, and to other publishe figures. The PMS instrument was also
used to measure sub-micron particles in metered-dose inhalers.<br>
</p>
<p>ACKNOWLEDGEMENTS. <br>
I should like to thank Glaxo Group Research Ltd. for the financial support for
this thesis.</p>
<p>I wish to express my sincere gratitude to my supervisors, particularly
Dr.
G. Hallworth, Professor S. S. Davis and Dr. C. G. Wilson for their considerable
advice and encouragement throughout this work. Thanks are also due to Dr. J.
M. Padfield, Dr. M. Frier, Mr A. Perkins and Dr. J. Hardy for their help and
advice. I also wish to thank the many members of staff both at Glaxo Group Research
Ltd. and the University of Nottingham who in their various ways have helped
my work.</p>
<p>My heartfelt thanks go to Miss Sharon Arnold for her proficient typing.
Finally, I wish to thank my husband Ian and my parents for their constant interest
and encouragement, and I dedicate this thesis to them.
</p>
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