Particulate Study on NeoProfen, a Neonatal Injectable Product.

Area of Science:

• Pharmaceutical Science
• Materials Science
• Neonatal Medicine

Background:

• NeoProfen (ibuprofen lysine) is a critical medication for closing patent ductus arteriosus in premature infants.
• Particulate matter was observed in NeoProfen vials during stability testing, leading to recalls.
• Neonatal patients are particularly vulnerable to drug product impurities due to immature organ systems.

Purpose of the Study:

• To identify the root cause of particulate matter formation in NeoProfen vials.
• To investigate the interaction between NeoProfen and Type I borosilicate glass.
• To develop corrective actions to ensure NeoProfen product quality and stability.

Main Methods:

• Inductively coupled plasma-mass spectrometry (ICP-MS)
• X-ray photoelectron spectroscopy (XPS)
• Scanning electron microscopy with energy dispersive X-ray spectrometry (SEM-EDS)
• Raman and Fourier transform infrared microspectroscopy (FTIR)

Main Results:

• Particulate matter identified as ibuprofen aluminum salts of varying stoichiometries.
• Mechanism involves ibuprofen anion reacting with the vial's aluminum oxide network.
• Formation of ibuprofen aluminum salts occurred over time within the Type I borosilicate glass vials.

Conclusions:

• The interaction between NeoProfen and Type I borosilicate glass causes particulate formation.
• An alternate Type I borosilicate glass vial with an interior coating prevents ibuprofen aluminum salt formation.
• The new vial packaging ensures NeoProfen quality and stability for neonatal use.