Solubilization of ibuprofen for freeze dried parenteral dosage forms

Abstract

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 ss-NMR. Analyses of lyophilized samples showed solubility enhancement of ibuprofen and in situ formation of an ibuprofen salt with the alkaline excipients used.

Freeze-Drying Ethylcellulose Microparticles Loaded with Etoposide for In Vitro Fast Dissolution and In Vitro Cytotoxicity against Cancer Cell Types, MCF-7 and Caco-2

“…These results strongly indicate that the use of the freeze-drying technique for the microparticles prepared in this study is a good technique to enhance the solubility of ETO and increase the release rate of ETO at pH 7.4. This finding is in agreement with the previously mentioned study, where the solubility of ibuprofen was significantly enhanced by using the freezedrying technique [37]. Similar results were obtained by Wei et al, who showed enhanced dissolution of microparticles loaded with poorly soluble drug nanocrystals: the hydroxypropyl cellulose (HPC) polymer used as a matrix carrier had a low viscosity.…”

Response of Rhodococcus cerastii IEGM 1278 to toxic effects of ibuprofen

“… 1 –ibuprofen sodium salt; 2 –ibuprofen; 3 –9-hydroxy ibuprofen; 4 –6,9-dihydroxy ibuprofen; 5 –6-hydroxy ibuprofen; 6 –decarboxylated derivative of 9-hydroxy ibuprofen; 7 –decarboxylated derivative of 6,9-dihydroxy ibuprofen; 8 –decarboxylated derivative of 6-hydroxy ibuprofen. The numbering of IBP atoms proposed by Preskar et al is used [ 88 ]. …”

Investigation of design space for freeze-drying injectable ibuprofen using response surface methodology

“…Two formulations were prepared with different isotonic agents: sodium chloride (NaCl) and mannitol. Both are commonly used but have very different characteristics (i.e., solubility, crystallization behavior and polymorphism) (4). The quantity of mannitol or NaCl was defined with respect to achieving osmolality criteria in a range of 280-320 mOsmol kg -1 of the reconstituted powder, and the quantity of l-arginine by pH criteria (following the optimal physiological pH of 7.4).…”

“…Various techniques for increasing the aqueous solubility of IBP in oral solid and liquid formulations described in the literature were briefly reviewed in our previous research (4). Each technique exhibits both advantages and disadvantages, and the choice depends on drug characteristics, pharmaceutical dosage form, and route of application (5), which in our case was freeze-dried powder for parenteral application.…”

“…Our previous work already demonstrated the development of a freeze-dried product with IBP with the capacity for intravenous (i.v.) application by simple reconstitution with a predetermined quantity of water for injection (WFI), without any need for additional isotonization (4). Despite the fact that the i.v.…”