Acta Pharm. 69 (2019) 17-32
Original research paper
Solubilization of
ibuprofen for freeze dried parenteral dosage forms
MAJA PRESKAR, TOMISLAV VRBANEC, FRANC VREČER,
PRIMOŽ ŠKET, JANEZ PLAVEC and MIRJANA GAŠPERLIN
maja.preskar@krka.biz
1 Krka d.d. Novo mesto, SI- 8000
Novo mesto, Slovenia
2 University of Ljubljana, Faculty
of Pharmacy, SI- 1000, Ljubljana, Slovenia
3 Slovenian NMR Center, National
Institute of Chemistry, SI-1000 Ljubljana, Slovenia
Accepted September 23, 2018
Published online October 29, 2018
Ibuprofen, a weakly acidic non-steroidal
anti-inflammatory drug having poor aqueous solubility, is a challenging drug
for the development of pharmaceutical formulations, resulting in numerous
research attempts focusing on improvement of its solubility and consequently
bioavailability. Most studies have been done for solid dosage forms, with very
little attention paid to parenterals. Hence, the main purpose of the present study
was to enhance ibuprofen solubility as a result of formulation composition and the
freeze drying process. Moreover, the purpose was to prepare a freeze dried
dosage form with improved ibuprofen solubility that could, after simple
reconstitution with water for injection, result in an isotonic parenteral
solution. Solubility of ibuprofen was modified by various excipients suitable
for parenteral application. Drug interactions with selected excipients in
the final product/lyophilisate were studied by a
combined use of XRPD, DSC, Raman and ssNMR. Analyses
of lyophilized samples showed solubility enhancement of ibuprofen and in situ formation of an ibuprofen salt
with the alkaline excipients used.
Keywords: ibuprofen,
solubility enhancement, freeze drying, physico-chemical
characterization