It's quite interesting when one reads of the "surveys" where either the US Food and Drug Administration (FDA) or state boards of pharmacy travel around obtaining samples of compounded drug preparations for analysis to confirm that the pharmacists are compounding in accordance with United States Pharmacopeia (USP) Chapter <795> Pharmaceutical Compounding-Nonsterile Preparations, where the standard is a +/- 10% variation that is allowed. The range from 90.0 to 110.0% of the labeled content must be met unless there is a specific monograph in the USP with a different standard which may be either greater than or less than the +/- 10%. As an example, if Hydrocortisone Gel USP or Hydrocortisone Lotion USP is compounded, the requirement is +/- 10%; but, if Amoxicillin Capsules USP are appropriately compounded, the range is from 90 to 120%; the standard for Procainamide Hydrochloride Injection USP is 95.0 to 105.0% and Riboflavin Injection USP is from 95.0 to 120.0%. However, most USP product monographs (as compared to substance monographs) have the standard range for both manufactured products and compounded preparations as 90.0 to 110.0%. It is important when results are reported as "out of specification" to determine whether or not there is an official USP-National Formulary (NF) monograph on the preparation that was compounded and tested.

Another difficulty, as previously reported in this column, is when commercial products are used as the source of the drug. As pharmacists, we only know that they meet the United States Pharmacopeial (USP) or FDA specifications; we don't know if the tablets, capsules, etc. used in compounding contain 90.1% of drug or 109.9% of the drug (almost a 20% difference). Consequently, the source of the out-of-specification compounded preparation may be the commercial product used and not the pharmacy manipulations. For example, if a commercial product can contain 90.0 to 110.0% active drug, and compounding pharmacists are allowed a 90.0 to 110.0% variation, then the overall variation that may theoretically occur is 0.90 � 0.90 = 0.81 or 81% and 1.10 � 1.10 = 1.21 or 121%. So, we now have a potential range of 81.0 to 121.0% that may occur if both the commercial product and pharmacy manipulations were in the low end, and the opposite if both entities were working at the high end. Therefore, in instances where commercial products are used in compounding and they are tested by a state board of pharmacy or the FDA, then the tolerance for their testing purposes should be 81.0 to 121.0%, not 90.0 to 110.0%. It should be noted, however, that even the USP does not recognize this as an option and the range of 90.0 to 110.0% for compounding is the standard.

Obviously, if USP-NF- or equivalent-grade bulk substances are used, the pharmacist is generally starting with substances with a standard generally ranging from 98.0 to 102.0%; this is much better to work with than 90.0 to 110.0% or even broader ranges for commercial products. The Certificate of Analysis is also available to provide the assay results for the specific lots of each substance that can be used for calculations, etc. during the compounding process.

Bottom line, bulk substances are the only rational source of drugs for ALL compounding activities, unless they are not available. Excipients in commercial dosage forms can also contribute to compatibility and stability problems as well as elegance and compliance considerations. For more information on interpreting laboratory results, etc., see Volume 2, Issues 1-8, Affectors of Laboratory Results, of the CompoundingToday.com newsletters.


Loyd V. Allen, Jr., Ph.D., R.Ph
Editor-in-Chief

The complete archives of the CompoundingToday.com newsletter are available to current CompoundingToday.com subscribers at http://CompoundingToday.com/Newsletter/ . The latest edition is always available free to the public!

An additional 46 citation abstracts on phenytoin and wound healing (24) and gastrointestinal topicals such as diaper dermatitis, anal fissures, and posthemorrhoidectomy pain (22) have been added to CompoundingToday.com's literature search database this week. Here is a sampling of them:

Topical phenytoin for wound healing.
Bhatia A, Prakash S. Dermatol Online J 2004; 10(1): 5.

Topical phenytoin in wound healing.
Pendse AK, Sharma A, Sodani A et al. Int J Dermatol 1993; 32(3): 214-217.

Topical phenytoin treatment of stage II decubitus ulcers in the elderly.
Rhodes RS, Heyneman CA, Culbertson VL et al. Ann Pharmacother 2001; 35(6): 675-681.

Pharmacological advancements in the treatment of chronic anal fissure.
Acheson AG, Scholefield JH. Expert Opin Pharmacother 2005; 6(14): 2475-2481.

Treatment of chronic anal fissure by application of L-arginine gel: A phase II study in 15 patients.
Gosselink MP, Darby M, Zimmerman DD et al. Dis Colon Rectum 2005; 48(4): 832-837.

A prospective randomized trial of diltiazem and glyceryl trinitrate ointment in the treatment of chronic anal fissure.
Bielecki K, Kolodziejczak M. Colorectal Dis 2003; 5(3): 256-257.

Need a valuable research tool to search for information on a specific medical topic? For complete, science-based information about medical topics, the National Library of Medicine's database of medical literature, MEDLINE, is an essential tool for the compounding pharmacist. IJPC's September/October 2006 issue includes a tutorial article on MEDLINE. The article discusses the main features required to perform a search and work with search results. See the complete listing of the issue's articles, including abstacts, at http://www.ijpc.com/editorial/SearchByIssue.cfm?PID=2439

Sign up today at www.IJPC.com and start your journal print and electronic subscriptions. You can download what you are currently subscribed to and purchase electronic access to our complete set of back issues.

Print Those Labels!
Don't use handwritten labels on materials, containers, or cabinets in your pharmacy; it looks unprofessional and presents a poor appearance. Label machines are inexpensive and available in either stand-alone units or those that can be used with a computer. They come in different sizes and have different features. Visit your local office supply store or go on-line and "professionalize" the appearance of the drawers, doors, and containers, etc. in your pharmacy.