Enteral suspension of nifedipine for neonates. Part 1. Formulation of nifedipine suspension for hospital use

Objective: To formulate nifedipine for paediatric use and to assess its con tent uniformity as well as the microbiological and physical stabilities of the hypromellose solution that was used in the formulation. Method: Six concentrations (0.5-3.0%) of hypromellose colloids and water as a blank were compounded with nifedipine, both as a powder and as crushed t ablets, to a concentration of 1 mg/mL. Four different screening tests were used to find the most homogenous and dose-accurate combination. First, nife dipine suspensions were stored in vials for one month and visual homogenity of the redispersed suspensions was observed. Second, the homogenity of the suspensions was studied by measuring the nifedipine concentration from upp er, middle and lower parts of the redispersed suspension. Next, the nifedip ine concentration was measured from the suspensions immediately, 1 min and 2 min after shaking to ensure dose accuracy during the administration perio d. Finally, suspensions were packaged into oral disposable syringes and nif edipine concentrations were determined after one month of storage. Content uniformity of the packaged single-dose syringe suspensions was studied acco rding to a method established by the European Pharmacopoeia. Microbiologica l stability, density, pH, osmolality, viscosity and surface tension of the hypromellose solution were studied over a 12-month storage period. Results: From the results of the screening tests of hypromellose solution, 1.0% hypromellose was chosen as the vehicle for nifedipine enteral suspensi ons, made from both crushed tablets and nifedipine powder. Nifedipine suspe nsions made from hypromellose 1.0% were easiest to redisperse as a homogeno us solution, and it also appeared best on visual inspection. The content un iformity of the suspension complied with the test recommended by the Europe an Pharmacopoeia. The 1.0% hypromellose solution was found to be microbiolo gically stable for 6 months and physically stable for 12 months.