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

Elena Tamburini,Maria Elena Maldonado Rodriguez,Federico Zappaterra,Bruno Semeraro,Stefania Costa,Daniela Summa

doi:10.3390/ijms22063066

Elena Tamburini, Maria Elena Maldonado Rodriguez + Show 4 more

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https://doi.org/10.3390/ijms22063066

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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.

Highlights

Ibuprofen ((R,S)-2-(p-isobutylphenyl)-propionic acid) is a traditional nonsteroidal anti-inflammatory drug (NSAID) [1] that was developed in the late 1960s [2] for the treatment of symptoms caused by arthritis such as swelling, pain, and stiffness [3]
For the covalent attachment of hydrophilic functional groups to this poorly soluble active ingredient, as a possible strategy for improving its solubility, we focused on lipaseactive ingredient, as a possible strategy for improving its solubility, we focused on lipasecatalyzed esterification of ibuprofen with sorbitol
Ibuprofen is a widely used NSAID limited in bioavailability by its poor water solubility

Summary

Introduction

Ibuprofen ((R,S)-2-(p-isobutylphenyl)-propionic acid) is a traditional nonsteroidal anti-inflammatory drug (NSAID) [1] that was developed in the late 1960s [2] for the treatment of symptoms caused by arthritis such as swelling, pain, and stiffness [3]. Like other nonsteroidal drugs such as ketoprofen and flurbiprofen, is widely used for its analgesic, anti-inflammatory, and antipyretic properties [4]. It is used for mild-to-moderate pain such as dysmenorrhea, headaches (including migraine), dental pain, postoperative pain, and pain caused by musculoskeletal/joint disorders, including osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis [5,6]. The chronic use by oral administration of a NSAID may cause gastric mucosal damage—more concretely, stomach ulceration, bleeding, and perforation [18]

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