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Compounding: Goal remains to fulfill unmet need


Aminoglycoside antibiotics (gentamicin, tobramycin and kanamycin) are inactivated when admixed with other antibiotics, particularly beta-lactams. This interaction is greatest with carbenicillin, followed by ticarcillin, penicillin G and ampicillin. Loss of potency by as much as 50 percent can occur within four to six hours. This interaction is a potential problem when antibiotic mixtures are prepared and dispensed for use several hours later. This interaction does not occur at therapeutic concentrations within the patient because the drugs are diluted in plasma and body fluids.

Drugs formulated as acids — such as the hydrochloride form of basic drugs — are designed to maintain their solubility in aqueous solutions. However, when these formulations are mixed with drugs that are basic, or are added to basic vehicles, drug precipitation may occur.

Several drugs are not soluble in aqueous vehicles. Therefore, they are dissolved in organic solvents (propylene or ethylene glycol) or alcohols. These are notoriously unpalatable to some animals, particularly cats. However, if these formulations are diluted in aqueous fluids, or aqueous flavorings added, precipitation may occur. When these are stored at home by the pet owner, precipitation of the drug to the bottom of the container results in the dosing of a dilute mixture when the container is sampled from the top and a highly concentrated mixture when the container is sampled from the bottom (assuming that the precipitate at the bottom can be re-suspended). This may be observed when mixing some drugs in aqueous fluids. For example if diazepam solution (which contains propylene glycol and alcohols) is diluted in saline solution or lactated Ringer's solution, precipitation occurs.

In some animals, transdermal delivery is ideal because it is convenient and bypasses the intestinal and hepatic first-pass effects. The medications most-often formulated for transdermal delivery to animals are antiparasitic drugs for cattle and anti-flea drugs for dogs and cats. Transdermal applications of human drugs also are used. One such delivery device consists of a patch containing a reservoir of fentanyl that is absorbed through the skin.

Unless the drug is highly lipophilic and formulated in a vehicle that has been shown to enhance transdermal penetration, it is difficult to attain systemic concentrations from transdermally-applied drugs. There have been several attempts by compounding pharmacies to formulate transdermal medications from existing forms of antibiotics, cardiovascular drugs, antithyroid drugs, analgesics, corticosteroids and antidepressants. Bulk drugs also have been used for transdermal compounding. Drugs have been combined with penetration enhancers to facilitate transdermal absorption. One popular example of a penetration enhancer is pluronic lecithin organogel (PLO), which is lecithin that is mixed with isopropyl palmitate and a poloxamer (pluronic).

The ingredients in PLO act as surfactants, emulsifiers and solubilizing agents. Although the use of PLO is popular among the veterinary compounding pharmacies, there are no successful commercial formulations that have combined PLO with systemic drugs. Drugs that have been applied to cats in a PLO vehicle include fluoxetine, glipizide, amitriptyline, methimazole, fentanyl, morphine, dexamethasone, diltiazem and buspirone.

Dr. Johnny Hoskins is owner of DocuTech Services. He is a diplomate of the American College of Veterinary Internal Medicine with specialities in small animal pediatrics. He can be reached at (225) 955-3252, fax: (214) 242-2200, or e-mail:

What's your question? Send your pediatric/geriatric related questions to: Pediatric/Geriatric Protocol, DVM Newsmagazine, 7500 Old Oak Blvd., Cleveland, OH 44130. Your questions will be answered by Dr. Hoskins in upcoming columns.


Source: DVM360 MAGAZINE,
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