M. Helin-tanninen et al., Enteral suspension of nifedipine for neonates. Part 1. Formulation of nifedipine suspension for hospital use, J CLIN PH T, 26(1), 2001, pp. 49-57
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.