Biocatalytic Approach for Direct Esterification of Ibuprofen with Sorbitol in Biphasic Media

Abstract

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) introduced in the 1960s and widely used as an analgesic, anti-inflammatory, and antipyretic. In its acid form, the solubility of 21 mg/L greatly limits its bioavailability. Since the bioavailability of a drug product plays a critical role in the design of oral administration dosage, this study investigated the enzymatic esterification of ibuprofen as a strategy for hydrophilization. This work proposes an enzymatic strategy for the covalent attack of highly hydrophilic molecules using acidic functions of commercially available bioactive compounds. The poorly water-soluble drug ibuprofen was esterified in a hexane/water biphasic system by direct esterification with sorbitol using the cheap biocatalyst porcine pancreas lipase (PPL), which demonstrated itself to be a suitable enzyme for the effective production of the IBU-sorbitol ester. This work reports the optimization of the esterification reaction.

Direct enantioselective α-alkylation of secondary acyclic amines with ketones by combining photocatalysis and lipase catalytic promiscuity

“…41 Thus, water molecules bound to the enzyme play a critical role in catalysis and act as a lubricant within the enzyme. 42 To verify the catalytic effect of the enzyme, some control experiments were performed. First, the non-enzyme proteins bovine serum albumin (BSA) and egg white albumin (EWA) were utilized as catalysts in the model reaction under the standard conditions, but no product was detected (Table 4, entries 7 and 8).…”

“…41 Thus, water molecules bound to the enzyme play a critical role in catalysis and act as a lubricant within the enzyme. 42…”

Xylitol as a Hydrophilization Moiety for a Biocatalytically Synthesized Ibuprofen Prodrug

“…where A ester is the area of the IBU-xylitol ester and A xylitol is the area of xylitol [63]. Negative controls of the reaction were prepared without the use of lipase and all of the experiments were conducted in triplicate.…”

Development and Validation of a Simple and Sensitive Reverse-Phase High Performance Liquid Chromatographic Method for the Determination of Ibuprofen in Pharmaceutical Suspensions

“…Ibuprofen (IBP); (±)-2-(p-isobutylphenyl) propionic acid was the first propionic acid derivative during the late 1960s 1 . Fig.…”