To Flavor or Not to Flavor Extemporaneous Omeprazole Suspension? M. C. Chuong, C. A. Taglieri, S. G. Kerr MCPHS University Purpose For those patients who have difficulty in swallowing, the oral suspension dosage form is an option. A previously published extemporaneous compounding method “Omeprazole 2-mg/mL Oral Liquid” (Int. J Pharmaceutical Compounding, 10(5):389, 2006) described emptying the contents of sufficient omeprazole capsules containing 200 mg of drug to mix with 100 mL of sodium bicarbonate 8.4% injection. The present study aimed to: (1) examine whether flavoring the suspension impacted its stability, and (2) compare the capability of detecting omeprazole degradation using either a Spherisorb C8 (USP L7) 10 cm (Waters) or a Zorbax StableBond cyano (USP L10) 15 cm column (Agilent). Methods The extemporaneous omeprazole suspension was compounded by seven third-year doctor of pharmacy students using the equipment and procedures described in compounding textbooks under the supervision of a registered pharmacist. The unflavored suspension was prepared by emptying the content of four 20-mg omeprazole DR capsules into a 2-oz Amber Plastic RX Bottle. After 40 mL of the 8.4% Sodium Bicarbonate Injection was added, the capped bottle was shaken periodically for 2-5 h until the pellets had dissolved. The product was refrigerated for a minimum of 4 h prior to HPLC study. The flavored extemporaneous suspension was prepared in the same manner as the unflavored suspension except for 0.45 mL addition of FlavorRX® grape to final composition of 1.125%. Neither group contained any sweetener. All samples were stored at 2-8oC, and the sampling was done at room temperature. The HPLC method was adopted from Omeprazole Monograph, USP-NF 2016. A phosphate buffer was prepared by mixing 0.725 g of monobasic sodium phosphate and 4.472 g of anhydrous dibasic sodium phosphate and deionized water to 1000.0 mL. Two hundred and fifty milliliters of this solution were further diluted with water to 1000.0 mL. The pH was adjusted with phosphoric acid to 7.6. The mobile phase was composed of acetonitrile and phosphate buffer in 1:3 v/v ratio. Diluent was made by mixing acetonitrile and 0.01 M sodium borate (pH 9.61) in 1:3 v/v ratio. Omeprazole USP RS was weighed and diluted with Diluent to 0.20 mg/mL. Five mL of compounded suspension taken from the Rx bottle of each group (flavored and unflavored) was diluted with Diluent to 50.0 mL. After sonication, mechanical shaking and vortexing, 10.0 mL of the suspension was centrifuged. One mL of its supernatant was loaded into a vial to provide the equilibrated HPLC system. The LC operating conditions included detector at 280 nm, flow rate at 0.8 mL/min and injection volume of 20 microliters. Results Manual shaking of the suspension was required prior to taking samples from plastic Rx bottles because the undissolved particles in the suspension were deposited at the bottom of the bottle during storage. The flavored suspension formed a twice-height of foam than in the unflavored suspension which was also more resilient after ten vigorous manual shakings. The chromatographic AUC of Omeprazole USP Reference Standard was 7301.8±87.2 (n=4). The tailing factor is 1.2. Using the Spherisorb C8 column, the chromatograms of the flavored extemporaneous suspensions showed abnormal fronting as early as Day 2. An unidentified degradant peak was observed at Day 13 and Day 16, but disappeared at Day 20. When the Zorbax SB-CN column (about C4 in chain length) was used to quantify the Day 16 and Day 20 flavored samples, a small unidentified peak was present in front of the drug peak. But the chromatographic peak shapes and AUC of the unflavored suspension remained unchanged significantly for up to Day 23 quantified using both Spherisorb and Zorbax columns. The average pH of the flavored suspensions was 8.37±0.433 (n=3), while that of the unflavored suspensions was 8.46±0.07 (n=3). Conclusion In addition to treating the symptoms of gastroesophageal reflux disease, Omeprazole has also been used to control the gastric side effects of various medications (e.g. Harvoni for treating hepatitis C genotype 1). Since omeprazole oral suspension requires refrigeration, conduction of single injection is preferred to sequence run to avoid prolonged exposure of the LC samples to room temperature in an autosampler. Although FlavorRX grape did not impact the suspension pH and the chromatographic retention time significantly, it did increase the formation of resilient foam, which could hinder dosing accuracy. Under the conditions used the study showed that the “flavored” compounded suspension chromatograms were not uniform up to the BUD (Beyond Use Date) of 14 days set by USP General Chapters: <795> Pharmaceutical Compounding - Nonsterile Preparations for water-containing oral formulations. Based on these results, pharmaceutical scientists and compounding pharmacists are advised against adding flavorant to an unsweetened oral suspension without initially checking for stability.