Stability of 5-Fluorouracil in an extemporaneously compounded ophthalmic solution.

5-Fluorouracil (5-FU) is used in the treatment of a variety of ophthalmic conditions, including glaucoma, pterygium, retinal detachment and premalignant eye lesions. Specifically for the treatment of pterygium, intravitreal injections of 5-FU have been extemporaneously compounded by pharmacists and typically stored in syringes. No data exist concerning the chemical and physical stability of these solutions. With this in mind, the stability of 5-FU (1mg/0.1mL) in 0.9% sodium chloride injection prepared in the hospital pharmacy laboratory at the University of South Carolina was studied with respect to time and temperature. Admixtures of 5-FU were aseptically prepared and stored in 1-mL tuberculin syringes. The stability of these solutions was evaluated in a freezer, in a refrigerator, at room temperature and in an oven set at 40 deg C. Immediately after prepareation, samples were collected to determine initial concentration using a stability-indicating high-performance liquid chromatography method and to assess the pH of the solution. The same tests were repeated after one, three, five and seven days of storage. Samples were also visually inspected at these times for signs of physical incompatibility. Tuberculin syringes stored at each of the temperatures showed no signs of physical incompatibility (precipitate) or loss of drug. There was also no appreciable change in pH of the solution over the study period. This study showed that aseptically prepared 5-FU ophthalmic solutions packaged in tuberculin syringes can be stored safely for up to seven days at temperatures ranging form -10 to 40 deg C/

Enhancement of skin penetration of nonsteroidal anti-inflammatory drugs from extemporaneously compounded topical-gel formulations.

Ketoprofen and ibuprofen topical gels were compounded with decyl methyl sulfoxide and the terpenes d-limonene, (-)-menthone, terpinen-4-ol, and a-terpineol as penetration enhancers. Transdermal penetration profiles for both ketoprofen and ibuprofen were determined using full-thickness human skin, modified Franz diffusion cells and an isotonic (pH7.4) phosphate buffer solution. Human skin was used in these experiments to approximate the therapeutic use of these gels. Ibuprofen was found to have superior transdermal kinetics when compared to ketoprofen. Ibuprofen is a smaller and more lipophilic molecule than ketoprofen, which gives it better penetration properties. All enhancers tested significantly increased the penetration (except (-)-menthone) and skin retention (except terpinen-4-ol) of ketoprofen. None of the enhancers tested significantly increased the penetration or retention of ibuprofen. Despite the lack of enhancer activity, ibuprofen still demonstrated higher skin penetration and retention than enhanced delivery of ketoproen. The results of these studies suggest that the addition of penetration enhancers can significantly increase the amount of ketoprofen penetration, while enhancers demonstrated no significant increase (and can actually decrease) the amount of ibuprofen penetrating into and through the skin.

Stability of vancomycin in an extemporaneously compounded ophthalmic solution.

The stability of vancomycin 31 mg/mL (as the hydrochloride) in an artificial tears solution at -10, 4, 25, and 40 degrees C was studied. Vancomycin power was reconstituted with sterile water for injection to a concentration of 50 mg/mL. Artificial tears solution containing 0.3% hydroxypropyl methylcellulose, 0.1% dextran 70, 0.01% benzalkonium chloride, and 0.05% edetate disodium was used to produce a final concentration of 31 mg/mL. Triplicate solutions for each storage temperature and sampling time were prepared. The solutions were stored at -10, 4, 25, and 40 degrees C. Samples were taken initially and at 3, 7, 10, 21, 30, 45, and 60 days for visual inspection and analysis by high-performance liquid chromatography. All solutions remained clear and colorless at -10, 4, and 25 degrees C throughout the study period. By day 3, crystalline particles formed in the solutions stored at 40 degrees C. No substantial change in pH was observed at any time. At -10 degrees C, the solutions retained more than 90% of their initial vancomycin concentrations throughout the study period. The solutions retained a mean of at least 90% of the initial drug concentration for 21 days at 4 degrees C and for 7 days at 25 degrees C. For the solutions stored at 25 or 40 degrees C, less than 85% of the initial vancomycin concentration remained after 10 and 3 days, respectively. Vancomycin 31 mg/mL (as the hydrochloride) in an artificial tears solution was stable for 45 days at -10 degrees C, 10 days at 4 degrees C, and 7 days at 25 degrees C in the tears solution's original container.