Compatibility of caffeine, carvedilol, clomipramine hydrochloride, folic acid, hydrochlorothiazide, loperamide hydrochloride, methotrexate, nadolol, naltrexone hydrochloride and pentoxifylline in SyrSpend SF PH4 oral suspensions

Abstract

ObjectivesThe objective of this study was to evaluate the compatibility of 10 commonly used active pharmaceutical ingredients (APIs) compounded in oral suspensions using a globally available suspending vehicle (SyrSpend SF PH4 liquid): caffeine 10.0 mg/mL, carvedilol 1.0 mg/mL, clomipramine hydrochloride 5.0 mg/mL, folic acid 1.0 mg/mL, hydrochlorothiazide 5.0 mg/mL, loperamide hydrochloride 1.0 mg/mL, methotrexate 2.5 mg/mL, nadolol 10.0 mg/mL, naltrexone hydrochloride 1.0 mg/mL and pentoxifylline 20.0 mg/mL, stored at both controlled refrigerated (2–8°C) and room (20–25°C) temperature.MethodsCompatibility was assessed by measuring the per cent recovery at different time points throughout a 90-day period. Quantification of the APIs was performed by high performance liquid chromatography (HPLC-UV) using a stability-indicating method.ResultsMethods were adequately validated. Forced degradation studies showed that at least one parameter influenced the stability of the APIs. All suspensions were assayed and showed API contents of between 90% and 110% over 90 days.DiscussionGiven the percentage of recovery of the APIs within the suspensions, the expiration date of the final products (API+vehicle) was found to be at least 90 days for all suspensions, for both controlled refrigerated and room temperature.ConclusionsThe results suggest that SyrSpend SF PH4 liquid is a stable suspending vehicle for compounding APIs from different pharmacological classes.

Preparation and Physicochemical Stability of Liquid Oral Dosage Forms Free of Potentially Harmful Excipient Designed for Pediatric Patients

“…Regardless of the type of storage conditions, the proportion of the initial concentration of dexamethasone, hydrochlorothiazide, phenytoin, or spironolactone remaining was within the limit set by the U.S. Pharmacopeia [26], meaning that the oral suspensions of each drug compounded using Syrspend® SF PH4 Dry were stable up to 60 days both at room temperature or under refrigeration. This result is similar to or greater than the stability period reported by others [9,10,11,12,13,14,15]. The physicochemical stability of the four oral liquid dosage forms was investigated for a period of 60 days since the microbiological stability of suspensions compounded using Syrspend® SF PH4 Dry has been demonstrated by the manufacturer over the same period [30].…”

“…To enable the appropriate volume of administration (preferably ≤1 mL for a newborn), according to the dose required in their therapeutic uses [6,8,28], we chose to prepare oral liquid dosage forms at a target concentration of 5 mg/mL for spironolactone, dexamethasone, and phenytoin and 2 mg/mL for hydrochlorothiazide. According to the literature, other authors have reported similar concentrations for oral liquid compounded preparations of the same APIs [10,13,15]. Some authors have proposed oral liquid dosage forms with lower strengths due to different therapeutic uses [12,14] or higher strengths since they were used in older children [9,11].…”

“…However, in many countries, formulations suitable for oral administration of these APIs to children are not currently commercially available. According to the literature, several methods to compound oral liquid preparations containing these APIs have been described [9,10,11,12,13,14,15]. These methods have used suspending vehicles formulated using suspending agents (sodium carboxymethylcellulose, xanthan gum), dispersant/humectants (propylene glycol, dimethicone), sweetening agents (sodium saccharin, sucrose), preservatives (methylparaben, propylparaben, sodium benzoate), and water as a solvent.…”

Compounded Nonsterile Preparations and FDA-Approved Commercially Available Liquid Products for Children: A North American Update

“… Carvedilol [12] is a racemic mixture where the S(-) enantiomer is a beta adrenoceptor blocker and the R(+) enantiomer is both a beta and alpha-1 adrenoceptor blocker. It is currently used to treat heart failure, left ventricular dysfunction, and hypertension.…”

Limited Influence of Excipients in Extemporaneous Compounded Suspensions

“…Compatibility results with SyrSpend SF have been published for more than 70 different APIs. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] In all of these studies, the compatibility was assessed by measuring the percentage recovery at varying time points throughout a 90-day period at controlled room and/or at controlled refrigerated temperature. The majority of the compatibility studies have been performed with raw pharmaceutical APIs.…”