The effects of substrate size, surface area, and density on coat thickness of multi-particulate dosage forms.
Drugs layering experiments were performed in a fluid bed fitted with a rotor granulator insert using diltiazem as a model drug. The drug was applied in various quantities to sugar spheres of different mesh sizes to give a series of drug-layered sugar spheres (cores) of different potency, size, and weight per particle. The drug presence lowered the bulk density of the cores in proportion to the quantity of added drug. Polymer coating of each core lot was performed in a fluid bed fitted with a Wurster insert. A series of polymer-coated cores (pellets) was removed from each coating experiment. The mean diameter of each core and each pellet sample was determined by image analysis. The rate of change of diameter on polymer addition was determined for each starting size of core and compared to calculated values. The core diameter was displaced from the line of best fit through the pellet diameter data. Cores of different potency with the same size distribution were made by layering increasing quantities of drug onto sugar spheres of decreasing mesh size. Equal quantities of polymer were applied to the same-sized core lots and coat thickness was measured. Weight/weight calculations predict equal coat thickness under these conditions, but measurable differences were found. Simple corrections to core charge weight in the Wurster insert were successfully used to manufacture pellets having the same coat thickness. The sensitivity of the image analysis technique in measuring particle size distributions (PSDs) was demonstrated by measuring a displacement in PSD after addition of 0.5% w/w talc to a pellet sample.
Heinicke
Grant
G
Formulation Development, Alpharma, Elizabeth, NJ 07207, USA. grant.heinicke@alpharma.com
Matthews
Frank
F
Schwartz
Joseph B
JB
D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004304:Dosage Forms; D010316:Particle Size; D013499:Surface Properties; D013608:Tablets, Enteric-Coated / Q000737:chemistry*
D004304:Dosage Forms; D013608:Tablets, Enteric-Coated