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Classification, Description, and Prevention of Errors
Compounding errors can be divided into the following categories:
- General Errors,
- Incorrect Ingredients,
- Incorrect Concentration,
- Incorrect Use of Equipment,
- Physicochemical Issues,
- Microbiological Contamination,
- Analytical Testing Issues,
- Microbiological Testing Issues, and
- Miscellaneous Errors.
Over the next several weeks, we will look at errors using the format or subject-headings of "Error Type," "Description," and "Avoiding the Error."
INCORRECT CONCENTRATION
| Error Type |
Description |
Avoiding the Error |
|---|
| Drug quantity or concentration too high |
A drug concentration that is too high can result from improper weights, incorrect form of the drug used, loss of vehicle during preparation (evaporation, loss from the weighing or measuring device or container during transfer, etc.), and improper packaging. |
See last week's comments ("Incorrect Ingredients") for improper drug form, weighing, measuring, and so on. Proper storage and use of proper packaging is critical. When using an ointment mill with a cream or a gel, the exposure to the atmosphere will result in some water or solvent loss and an increase in the actual drug concentration; the loss needs to be corrected by adding it back into the formulation after milling. Use of excessive heat resulting in loss of vehicle can occur with some formulations, which results in an increased drug concentration. Lower heat, covers on beakers, and so on can help. |
| Drug quantity or concentration too low |
A drug concentration that is too low can result from improper weights, use of the incorrect form of the drug, improper vehicle measurement, use of hygroscopic or deliquescent powders during weighing, incomplete emptying of weighing devices during transfer of the active drug, sorption (adsorption and/or absorption) of the active drug to the container walls (syringe walls or plunger tip, etc.) and so on. |
See last week's comments ("Incorrect Ingredients"). Also, when weighing hygroscopic or deliquescent powders, observe caution when performing the activity in a low humidity room in order to prevent the materials from taking up moisture from the air and increasing the weight while decreasing the actual amount of API obtained. Care in transferring chemicals (powders, semisolids, liquids, etc.) is of utmost importance to ensure all the material has been completely obtained. Sorption problems can generally be found in the literature; they mainly involve very potent, low concentration drugs. Also, when one mixes liquids and some semisolids, excessive air can become entrapped in the preparations, hampering efforts to qs to final volume. Mix the ingredients to minimize any incorporation of air into the preparation. An occasional issue occurs in the use of a nonsolvent to make a liquid dilution of a potent drug; confirming that the potent drug is soluble in the liquid used for the dilution can eliminate this issue. Also, the proper alcohol and solvent concentrations must be maintained for ensuring complete solubility of the API in a solution dosage form. When working with alcohol and water, maintain as high an alcohol concentration as possible by adding the water to the alcohol solution, not the reverse. When pipets and micropipets are used, insufficient volume will be delivered if the user is not aware of how to correctly use the pipet. |
| Use of incorrect excipients |
Analytical results from laboratories have reported out-of-specification (OOS) results when using manufactured drug products as the drug source. |
Compounding pharmacists do not have access to the actual analyzed concentration or quantity of drug in a specific manufactured dosage form. Furthermore, with USP tolerances ranging up to 80% to 120% and even greater, a compounding pharmacist does not know the actual quantity of drug in the capsules, injections, and so on that are used as the drug source in compounding. Because compounding allows only a 90%–110% variation, one can easily understand that the finished compounded preparation may be outside the acceptable range through no fault of the compounding pharmacist. |
| Stratification and lack of uniform appearance |
If heated semisolids are poured into containers while hot, they may tend to separate and stratify. Separation can also occur among particles that are different in size and density. |
For semisolids, allow the mixture to cool to just above the congealing point before pouring it into containers. For powders, reduce them to the same particle size range before mixing |
| Lack of uniformity of capsule weights |
Improperly filled capsules will result in several capsules being outside the acceptable weight range. |
When filling capsules at the powder incorporation stage, keep the spatula or plastic card in a vertical position as it is moved over the capsules holes to allow the powder to fall into the cavities, and tamp lightly. Then repeat until all capsules are uniformly filled. Do not slant the spatula or plastic card at an angle to force the powder in the holes because the filling will be nonuniform and result in weights that are outside the range. Allow the powder to simply fall into the capsule openings of its own weight. |
| Improperly filled or nonuniform suppositories or medication sticks |
Contraction or dimpling of suppositories and medication sticks results in insufficient preparation for each dosage form. |
Contraction or dimpling occurs when the melt is poured while too hot. Allow the melt to cool to just above its congealing point, and then pour it into the molds. |
| Missing drug |
Occasionally, a drug product that has been analyzed has been reported to have no API in the prescription. |
For each ingredient, exercise care in obtaining, weighing and measuring, and so on in order to eliminate this potential error. Generally, when weighing ingredients, observe good practice by placing the ingredients on one side of the balance and, as each is weighed, moving it to the opposite side or to a different location. Marking the weigh boats has also been useful. |
Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy Twenty-second edition
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