JANUARY 13, 2011
Martin A. Erickson III, RPh
Q: I compound some capsule formulations consistently and regularly. My supplier sent an excipient (methylcellulose derivative) that has a different density than the one I was using. Why are the densities not consistent? May I ask a supplier to only send 1 density consistently?
A: The manufacturing process for the cellulose will not yield a narrowly defined (exact, in this case) bulk density. Tight control of this property is not possible. Moreover, particle size/bulk density are not chemical properties, but are physical properties that are interdependent and can change with material handling. USP specifications are for “ranges,” as well: it’s a matter of practicality. The information is not included in Certificates of Analysis, but is found on the product label.
Since USP/NF, FDA, and State Boards of Pharmacy contemplate that compounded preparations are for individual patients on individual prescriptions, it would be very difficult to request or even argue for an exact bulk density, particle size, etc. Such specification could raise concern that the pharmacist intends to manufacture under guise of compounding, which of course, you are not about to do.
A manufacturer preparing capsules in large batches (eg, hundreds of thousands) could order ingredients and specify “all from same batch,” then recalculate the formulation according to the data for that particular lot. Since pharmacists are not manufacturers, but compounders, that is neither practical nor cost-effective for an individual pharmacy.
I suggest approaching it from the other direction: calculate and set up a spreadsheet that can be disseminated and used to determine the amount of excipient in a particular formulation based on laboratory practical (experimental) determination. That way, interpretation of the displacement(s) will be consistent, and the temptation to “shortcut” by ignoring the differences among lots will be minimized. PT
Mr. Erickson is director of professional affairs at Gallipot Inc.