Ian Sanderson's 1986 Thesis


Well out of date but some interesting bits if you are into tablet formulation. I thought the best was the use of Technicium in water penetration studies. Most use now is to provide the odd supporting reference for any papers on similar formulation studies..

Do bear in mind that all the computer stuff had to be on a mainframe & we'd only just progressed past punch tapes - Windows 3 may have existed but hadn't found its way to Nottingham at the time and all the typing up was done on a BBC with a 180k disc drive! The gamma camera had a floppy drive with discs about a foot across.

Enjoy.

Table of Contents

ABSTRACT
Two model direct compression tablet formulations have been examined by means of factorially designed experiments. The formulations were based on a direct compression vehicle (Avicel) containing 25%w/w of either paracetamol or aspirin. A disintegrant (maize starch), a lubricant (magnesium stearate) and a glidant (Aerosil) were also included. The influence of changes in mixing time and compaction pressure were used to represent changes in the manufacturing process. Alterations to the starch concentration and the drug particle size were chosen to reflect formulation changes. The coefficient of weight variation, porosity, tensile fracture stress, friability, the time for 50% liquid saturation of the tablets, and 90% of drug dissolution were used to monitor the effects of the changes.
The lubricant distribution, as determined by the mixing time, was found to control the tablet strength to a greater extent than the other factors. With the paracetamol formulations, where the particle size was similar to the bulk of the excipients, the particle size also had an appreciable effect on the tablet strength. The compaction pressure was the least effective factor.
A novel method of measuring liquid uptake into tablets based on gamma scintigraphy showed that the penetration into aspirin tablets was largely determined by the tablet strength. The uptake into paracetamol tablets was controlled by the drug particle size and the mixing time.
Increasing the starch concentration increased the dissolution rate, but this has been postulated to be due to an interaction of the starch with the drug surface rather than any disintegrant action. The drug particle size had a significant effect on the dissolution of the paracetamol tablets where the larger size dissolved more rapidly. There was little effect on the aspirin tablets where the drug size was greater than that of the other excipients.

ACKNOWLEDGEMENTS.
This work would not have been possible without the support and encouragement of Dr. J. W. Kennerley and Dr. G. D. Parr, to whom I would like to express my thanks. Any experimental work requires the maintenance of equipment, the procurement of apparatus and space to carry out those experiments. To this end I would also like to express my thanks to the technical staff of the Pharmacy Department at Nottingham University, not forgetting those concerned with the administration. A large proportion of this project has been concerned with the statistical analysis of results and I would like to thank Mr. P. Riley for his invaluable advice on experimental design and analysis. Thanks also to the other members of staff in Cripps Computing Centre at Nottingham University. The finance provided by the S.E.R.C. in conjunction with E. R. Squibb and Sons Ltd. made the project feasible.
Finally I would like to thank Ann for smoothing out the rough patches.