Extemporaneous indomethacin oral suspension prepared from injectable ampoules for therapy in premature infants and paediatric patients

Abstract

Indomethacin (IND) is used for off-label prescription for the treatment of patent ductus arteriosus (PDA) in premature infants. In Argentina, IND is only available as a suppository, dermic cream, injectable ampoules, and delayed-release capsules. Aiming to improve paediatric treatment and minimise the risk associated with improper dosage, this work focused on the development of an extemporaneous 0.2% IND oral suspension, starting from the commercially injectable formulation. Two 150mL batches of suspension were prepared using GRAS excipients. The suspensions were stored for 17 days at room temperature. Physical stability, morphological analysis of suspended particles, sedimentation volume, easy re-suspension, and dynamic viscosity were studied. The IND content, dissolution studies and microbiological attributes of non-sterile pharmaceutical products were also evaluated. After 17 days of storage, the suspension was easily re-dispersed after 15 s of simple hand-shaking. There were no detectable changes in colour, odour, and/or flavour. The suspension showed minimal changes in pH, viscosity, shape, and mean size of the suspended IND particles. The content uniformity and drug dissolution remained within the acceptable range during storage. This oral liquid suspension is an interesting alternative to be prepared by hospital pharmacy services for optimising the paediatric treatment of PDA.