Compounding Hotline

Pharmacy Times
Volume 75
Issue 12

Mr. Erickson is director of professional affairs at Gallipot Inc.

Your Compounding Questions Answered


The bulk powder lot I received this time doesn’t dissolve as fast as the last lot, and the powder looks more crystalline than before.


Manufacturers use various means to extract a chemical for bulk sale, sometimes leading to variations in physical appearance. For example, a monograph description might be: “fine, white, crystalline powder.” The definitions of these terms can vary—what is “fine” to one person might be a coarse powder to another, and “crystalline” can mean that it is obviously crystalline or only obviously crystalline upon microscopic examination. In any case, the compounder should call the supplier if any questions arise as to the identity of a bulk drug substance. To answer the solubility question, the following might be helpful:

When considering the structure and solubility of gabapentin and ketamine, for example, it is important to recall that solubility has 2 different components: it depends upon thermodynamic effects (add heat to dissolve faster) and also upon kinetic effects (sonicate to dissolve faster). The prime directive here when compounding is to reduce particle size with a Wedgwood or ceramic (not glass) mortar and pestle. Particle size reduction that aims for particle size uniformity will overcome or at least attenuate many compounding problems (grittiness, solubility issues, etc). Particle size reduction must be performed before attempting to dissolve the material.

It is important to recognize that complete dissolution is not required in every case. For example, gabapentin and ketamine frequently are used as active ingredients in topical preparations to treat peripheral neuropathies. When compounding those preparations, it is only necessary to make a slurry or paste of the active ingredients and any solid/particulate excipients so that they will be dispersed uniformly throughout the preparation.

E-mail your compounding questions to:

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