Stability of Azathioprine, Clonidine Hydrochloride, Clopidogrel Bisulfate, Ethambutol Hydrochloride, Griseofulvin, Hydralazine Hydrochloride, Nitrofurantoin, and Thioguanine Oral Suspensions Compounded with SyrSpend SF pH4. 2020

Hudson Polonini, and Sharlene Loures da Silva, and Carolina Neves Cunha, and Anderson de Oliveira Ferreira, and Korina Anagnostou, and Eli Dijkers
Fagron BV, Rotterdam, The Netherlands. hudson.polonini@fagron.com.

To allow for tailored dosing and overcome swallowing difficulties, compounded liquid medication is often required in pediatric patients. The objective of this study was to evaluate the stability of oral suspensions compounded with SyrSpend SF PH4 and the commonly used active pharmaceutical ingredients azathioprine (powder) 50 mg/mL, azathioprine (from tablets) 50 mg/mL, clonidine hydrochloride (powder) 0.1 mg/mL, clopidogrel bisulfate (from tablets) 5 mg/mL, ethambutol hydrochloride (powder) 50 mg/mL, ethambutol hydrochloride (from tablets) 50 mg/mL, ethambutol hydrochloride (powder) 100 mg/mL, griseofulvin (powder) 25 mg/mL, hydralazine hydrochloride (powder) 4 mg/mL, nitrofurantoin (powder) 10 mg/mL, and thioguanine (powder) 2.5 mg/mL. Suspensions were compounded at the concentrations listed above and stored at controlled room and refrigerated temperatures. Stability was assessed by measuring the percentage recovery at 0 day (baseline), and at 7 days, 14 days, 30 days, 60 days, and 90 days. Active pharmaceutical ingredients quantification was performed by high-performance liquid chromatography, via a stability-indicating method. The following oral suspensions compounded using SyrSpend SF PH4 as the vehicle showed a beyond-use date of 90 days when stored both at room or refrigerated temperatures: clonidine hydrochloride 0.1 mg/mL, ethambutol hydrochloride 50 mg/mL and 100 mg/mL, griseofulvin 25 mg/mL, nitrofurantoin 10 mg/mL, and thioguanine 2.5 mg/mL, all compounded from the active pharmaceutical ingredients in powder form. Suspensions compounded using the active pharmaceutical ingredients from tablets presented a lower beyond-use date: 30 days for ethambutol hydrochloride 50 mg/mL and hydralazine hydrochloride 4 mg/mL, stored at both temperatures, and for clopidogrel bisulfate 5 mg/mL when stored only at refrigerated temperature. Azathioprine suspensions showed a beyond-use date of 14 days when compounded using active pharmaceutical ingredients in powder form at both temperatures. This suggests that SyrSpend SF PH4 is suitable for compounding active pharmaceutical ingredients from different pharmacological classes.

UI MeSH Term Description Entries
D009582 Nitrofurantoin A urinary anti-infective agent effective against most gram-positive and gram-negative organisms. Although sulfonamides and antibiotics are usually the agents of choice for urinary tract infections, nitrofurantoin is widely used for prophylaxis and long-term suppression. Furadantin,Furadantine,Furadoine,Furadonine,Furantoin,Macrodantin,Nitrofurantoin Sodium Salt,Nitrofurantoin, Monohydrate
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D003000 Clonidine An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION. Catapres,Catapresan,Catapressan,Chlophazolin,Clofelin,Clofenil,Clonidine Dihydrochloride,Clonidine Hydrochloride,Clonidine Monohydrobromide,Clonidine Monohydrochloride,Clopheline,Dixarit,Gemiton,Hemiton,Isoglaucon,Klofelin,Klofenil,M-5041T,ST-155,Dihydrochloride, Clonidine,Hydrochloride, Clonidine,M 5041T,M5041T,Monohydrobromide, Clonidine,Monohydrochloride, Clonidine,ST 155,ST155
D004355 Drug Stability The chemical and physical integrity of a pharmaceutical product. Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D004977 Ethambutol An antitubercular agent that inhibits the transfer of mycolic acids into the cell wall of the tubercle bacillus. It may also inhibit the synthesis of spermidine in mycobacteria. The action is usually bactericidal, and the drug can penetrate human cell membranes to exert its lethal effect. (From Smith and Reynard, Textbook of Pharmacology, 1992, p863) Dexambutol,EMB-Fatol,EMB-Hefa,Etambutol Llorente,Ethambutol Hydrochloride,Etibi,Miambutol,Myambutol,EMB Fatol,EMB Hefa,Hydrochloride, Ethambutol,Llorente, Etambutol
D006118 Griseofulvin An antifungal agent used in the treatment of TINEA infections. Fulvicin-U-F,Grifulvin V,Gris-PEG,Grisactin,Grisefuline,Fulvicin U F,FulvicinUF,Gris PEG,GrisPEG
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006830 Hydralazine A direct-acting vasodilator that is used as an antihypertensive agent. Hydrallazin,Apresoline,Apressin,Apressoline,Hydralazine Hydrochloride,Hydralazine mono-Hydrochloride,Hydrazinophthalazine,Nepresol,Hydralazine mono Hydrochloride,Hydrochloride, Hydralazine,mono-Hydrochloride, Hydralazine
D000077144 Clopidogrel A ticlopidine analog and platelet purinergic P2Y receptor antagonist that inhibits adenosine diphosphate-mediated PLATELET AGGREGATION. It is used to prevent THROMBOEMBOLISM in patients with ARTERIAL OCCLUSIVE DISEASES; MYOCARDIAL INFARCTION; STROKE; or ATRIAL FIBRILLATION. Clopidogrel Besilate,Clopidogrel Besylate,Clopidogrel Bisulfate,Clopidogrel Hydrochloride,Clopidogrel Napadisilate,Clopidogrel Sandoz,Clopidogrel, (+)(S)-isomer,Clopidogrel-Mepha,Iscover,PCR 4099,PCR-4099,Plavix,SC 25989C,SC 25990C,SR 25989,Clopidogrel Mepha

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