ABSTRACT
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.
Subject(s)
Azathioprine/pharmacology , Clonidine , Griseofulvin/chemistry , Thioguanine , Administration, Oral , Azathioprine/chemistry , Child , Chromatography, High Pressure Liquid , Clonidine/chemistry , Clonidine/pharmacology , Clopidogrel/chemistry , Drug Stability , Ethambutol/chemistry , Humans , Hydralazine/chemistry , Nitrofurantoin/chemistry , Starch/chemistry , Suspensions , Thioguanine/chemistry , Thioguanine/pharmacologyABSTRACT
There are a substantial amount of suppliers for roller mills in the market, but there is a lack of scientific evidence of a roller mill's capacity to improve particle size reduction/distribution or homogenization. In this concise paper, we evaluate the use a roller mill in the final steps of compounding semisolid dosage forms. We performed three simple tests to verify these claims: 1) particle size evaluation through dynamic light scattering and scanning electron microscopy techniques, 2) content uniformity through high-performance liquid chromatography technique, and 3) cross contamination through a cleaning validation method. Dynamic light scattering and scanning electron microscopy techniques of benzoyl peroxide 5% (gel) and testosterone 1% (cream) showed a significant reduction on particle diameter. Content uniformity testing of creams containing progesterone 5%, estradiol 0.1%, and estriol 0.4% showed better homogeneity when using the roller mill. Finally, the proposed cleaning procedure decreased the presence of the compounded preparation to a "none-detection" level after the procedure. This suggests that the roller mill used does, in fact, play a role in the final aspect and quality of pharmaceutical semisolid dosage forms.
Subject(s)
Drug Compounding , Estriol , Pharmacy , Progesterone/chemistry , Chromatography, High Pressure Liquid , Estriol/chemistry , Particle SizeABSTRACT
Compounded liquid medication is frequently required in children to allow easy dose adjustment and overcome swallowing difficulties. 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 baclofen 2.0 mg/mL, carvedilol 5.0 mg/mL, hydrochlorothiazide 2.0 mg/mL, mercaptopurine 10.0 mg/mL, methadone hydrochloride 10.0 mg/mL, oseltamivir phosphate 6.0 mg/mL, phenobarbital 9.0 mg/mL and 15.0 mg/mL, propranolol hydrochloride 0.5 mg/mL and 5.0 mg/mL, pyrazinamide 100.0 mg/mL, spironolactone 2.0 mg/mL and 2.5 mg/mL, sotalol hydrochloride 5.0 mg/mL, tacrolimus monohydrate 0.5 mg/mL, ursodeoxycholic acid 20.0 mg/mL, and vancomycin hydrochloride 25.0 mg/mL. Suspensions were compounded with raw powders, except for mercaptopurine, pyrazinamide, and sotalol hydrochloride, which were made from commercial tablets. Stability was assessed by measuring the percentage recovery at 0 (baseline), 60 days, and 90 days after compounding for suspensions made with raw powders, which were stored at 2ÅãC to 8ÅãC. The stability of tablets, which were stored at 2ÅãC to 8ÅãC and 20ÅãC to 25ÅãC, was assessed by measuring the percentage recovery at 0 (baseline), 7 days, 14 days, 30 days, 60 days, and 90 days. Active pharmaceutical ingredients quantification was performed by ultraviolet high-performance liquid chromatography via a stability-indicating method. Given the percentage of recovery of the active pharmaceutical ingredients within the suspensions, the beyond-use date of the final products (active pharmaceutical ingredients + vehicle) was at least 90 days for all suspensions in the conditions tested. This suggests that SyrSpend SF PH4 is suitable for compounding active pharmaceutical ingredients from different pharmacological classes.
Subject(s)
Baclofen/chemistry , Carvedilol/chemistry , Hydrochlorothiazide/chemistry , Mercaptopurine/chemistry , Methadone/chemistry , Oseltamivir/chemistry , Pharmaceutical Vehicles/chemistry , Phenobarbital/chemistry , Propranolol/chemistry , Sotalol/chemistry , Spironolactone/chemistry , Starch/chemistry , Tacrolimus/chemistry , Ursodeoxycholic Acid/chemistry , Vancomycin/chemistry , Administration, Oral , Baclofen/administration & dosage , Carvedilol/administration & dosage , Drug Compounding , Drug Stability , Hydrochlorothiazide/administration & dosage , Hydrogen-Ion Concentration , Mercaptopurine/administration & dosage , Methadone/administration & dosage , Oseltamivir/administration & dosage , Pharmaceutical Solutions , Phenobarbital/administration & dosage , Propranolol/administration & dosage , Pyrazinamide/administration & dosage , Sotalol/administration & dosage , Spironolactone/administration & dosage , Suspensions , Tacrolimus/administration & dosage , Temperature , Time Factors , Ursodeoxycholic Acid/administration & dosage , Vancomycin/administration & dosageABSTRACT
The objective of this study was to evaluate the stability of 7 commonly used active pharmaceutical ingredients compounded in oral suspensions using an internationally used suspending vehicle (SyrSpend SF PH4): acetazolamide 25.0 mg/mL, baclofen 10.0 mg/mL, dipyridamole 10.0 mg/mL, mebeverine hydrochloride 10.0 mg/mL, propylthiouracil 5.0 mg/mL, quinidine sulfate 10.0 mg/mL, and topiramate 5.0 mg/mL. All suspensions were stored both at controlled refrigerated (2°C to 8°C) and room temperature (20°C to 25°C). Stability was assessed by measuring the percentage recovery at varying time points throughout a 90-day period. Active pharmaceutical ingredient quantification was performed by ultraviolet (UV) high-performance liquid chromatography, via a stability-indicating method. Given the percentage of recovery of the active pharmaceutical ingredients within the suspensions, the beyond-use date of the final products (active pharmaceutical ingredient + vehicle) was at least 90 days for all suspensions with regards to both temperatures. This suggests that SyrSpend SF PH4 is suitable for compounding active pharmaceutical ingredients from different pharmacological classes.
