Stability of dexamethasone, hydrochlorothiazide, phenytoin and spironolactone oral suspensions compounded with additives-free suspending vehicle
2 INSERM CIC 1402 axe HEDEX, Université de Poitiers, Faculté de médecine et de pharmacie, Poitiers
Administration of oral medicines to infants and young children remains a challenge to physicians and nurses. Oral suspensions provide a good alternative to solid forms (easy to administrate, dosage adjustment…). There are many suspending vehicles allowing to compound oral suspensions but almost all of them contain potentially harmful excipients (sodium benzoate, parabens…) that may prohibit their administration to neonates. To figure out this issue, a recent alternative has been commercialized: Syrspend® SF PH4 Dry, which do not contain any potentially harmful excipients.
The purpose of this study is to assess the physicochemical stability or four active pharmaceutical ingredients (API) (dexamethasone, hydrochlorothiazide, phenytoin and spironolactone) compounded with Syrspend® SF PH4 Dry.
Material and methods
Oral suspensions at 5 mg/mL (dexamethasone, phenytoin, spironolactone) and 2 mg/mL (hydrochlorothiazide) were prepared by mixing API powder with Syrspend® SF PH4 Dry, then by adding sterile water and shaking until homogeneity was achieved. Three batches of each API suspension were stored at room temperature and three at +4°C, in amber glass bottles.
A stability-indicating HPLC-UV method was developed, according to ICH Q2(R1) international guidelines, to determine API concentration at day 0, 7, 14, 28, 42 and 60). Osmolality, pH and organoleptic properties were also determined.
Regarding validation, the HPLC-UV method was linear with all API (r² ≥ 0,997 and residual values < 5,06%), and accurate according to the quality controls performed (CV < 4,42% for precision, and recovery rate remained 2% around the nominal value for trueness).
Regarding the stability study, API concentrations remained around 10% of the initial concentration (maximum deviation: 6,35%), whatever the API and the storage conditions used. No degradation products were observed. Less than 0,4 pH unit variations were observed and there were no organoleptic property modifications. Finally, no significative variation of the osmolality was observed since measurements were always below the LOQ (100 mOsm/kg).
Discussion and conclusion
This study demonstrates, whatever the API assessed, the physicochemical stability of oral suspensions compounded with Syrspend® SF PH4 Dry, over a 60 days period. Regarding the composition of this suspending vehicle (no alcohol, no sorbitol and parabens free), it provides a convenient alternative to other suspending vehicles, especially in neonates. Nevertheless, further experiments are required to assess microbiologic stability of suspensions compounded with Syrspend® SF PH4 Dry.