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

OBJECTIVE

To formulate an oral suspension of nifedipine for paediatric use and to assess its content 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 tablets, to a concentration of 1 mg/mL. Four different screening tests were used to find the most homogenous and dose-accurate combination. First, nifedipine 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 upper, middle and lower parts of the redispersed suspension. Next, the nifedipine concentration was measured from the suspensions immediately, 1 min and 2 min after shaking to ensure dose accuracy during the administration period. Finally, suspensions were packaged into oral disposable syringes and nifedipine concentrations were determined after one month of storage. Content uniformity of the packaged single-dose syringe suspensions was studied according to a method established by the European Pharmacopoeia. Microbiological 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 suspensions, made from both crushed tablets and nifedipine powder. Nifedipine suspensions made from hypromellose 1.0% were easiest to redisperse as a homogenous solution, and it also appeared best on visual inspection. The content uniformity of the suspension complied with the test recommended by the European Pharmacopoeia. The 1.0% hypromellose solution was found to be microbiologically stable for 6 months and physically stable for 12 months.