- CONDITION CENTERS
Compounding using commercial drugs as the source of medication can result in medication errors being inadvertently committed.
The standard for the allowed variation in compounded preparations is 90% to 110% of the active ingredient, as presented in the United States Pharmacopeia (USP). This range of the labeled content must be met unless there is a specific monograph in the USP with a different standard that 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 it is 95.0% to 105.0%, and for riboflavin injection USP it is from 95.0% to 120.0%.
Most USP product monographs, however, as compared with substance monographs, have the standard range for both manufactured products and compounded preparations as 90.0% to 110.0%.
As pharmacists, we only know that commercial products must meet either the USP or FDA specifications. What we do not know is if the tablets, capsules, etc, used in compounding contain 90.1% of the drug or 109.9% of the drug (almost a 20% difference); or even 119% of the drug, as given in the amoxicillin example above. Consequently, even though extreme care is taken during a compounding procedure, the final compounded preparation may be "out of specification" and may not meet the required standards.
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 resulting from weighing, manipulations, etc, then the overall variations that may theoretically occur are 81% (0.90 x 0.90 = 0.81) and 121% (1.10 x 1.10 = 1.21).
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. It should be noted, however, that the USP standard does not recognize this as an option, and the range of 90.0% to 110.0% for compounding is the standard.
Another potential source of compounding error in intravenous admixture programs is "overfill" that is allowed in ampoules, vials, and large-volume parenterals. For example, in a 1-mL container of an injection, an excess of 0.1 mL for a mobile liquid and 0.12 mL for a viscous liquid is allowed (10% or 12%).
For a 10-mL vial, the recommended excess is 0.5 mL for a mobile liquid and 0.7 mL for a viscous liquid. For containers larger than 50 mL, the excess may be 2% for mobile liquids and 3% for viscous liquids.
As is evident, it becomes important to accurately measure the quantity of drug required and not simply use the entire contents of the container (vial, ampoule, etc).
In the case of large-volume parenterals, when adding the exact quantity of drug, the actual "concentration" may be less than what is ordered due to the overage allowed in the 5% dextrose injection or the 0.9% sodium chloride injection. It is important to determine if the "concentration" is critical (and related to the rate of administration), or if the "total quantity of drug administered" is the critical factor.
Obviously, if USP-NF or equivalent-grade bulk substances are used, the pharmacist is starting with substances with a standard generally ranging from 98.0% to 102.0%. 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.
The 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 also can contribute to compatibility and stability problems as well as elegance and compliance considerations.
Lastly, plastic disposable syringes are designed to measure the quantity of a finished product or preparation. They are not designed to measure "ingredients" for compounding. If used for compounding intravenous admixtures or other preparations, they should be checked and calibrated prior to use, because this can be another potential source of error.
Dr. Allen is editor-in-chief of the International Journal of Pharmaceutical Compounding.
This article was contributed by: International Journal of Pharmaceutical Compounding and CompoundingToday.com