Guanidinylated Chitosan as a Multifunctional Enhancer for Improved Flurbiprofen Delivery

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Low-molecular-weight chitosan (CS) is a biopolymer with potential pharmaceutical applications.
• Modifying CS into guanidinylated chitosan (GCS) may enhance its properties as a drug delivery excipient.
• Poorly water-soluble drugs often exhibit limited bioavailability and gastrointestinal side effects.

Purpose of the Study:

• To evaluate guanidinylated chitosan (GCS) as a multifunctional excipient for improving the solubility and absorption of poorly water-soluble drugs.
• To compare the performance of GCS-based formulations with unmodified chitosan (CS) using flurbiprofen (FP) as a model drug.

Main Methods:

• Preparation of kneaded dispersions of flurbiprofen with GCS (FP-GCS) and CS (FP-CS).
• In vitro solubility and dissolution testing in water, simulated gastric fluid (pH 1.2), and simulated intestinal fluid (pH 6.8).
• In vivo pharmacokinetic studies in rats and gastric ulceration assessment in a rat ulcer model.

Main Results:

• Both GCS and CS increased flurbiprofen solubility concentration-dependently, with no significant difference between them.
• FP-GCS significantly enhanced flurbiprofen dissolution rate in water and simulated gastric fluid, but not in simulated intestinal fluid.
• In vivo studies showed FP-GCS achieved the highest plasma concentration of flurbiprofen and markedly reduced gastric ulceration in rats.

Conclusions:

• Guanidinylated chitosan (GCS) is an effective oral drug delivery excipient.
• GCS improves the bioavailability and gastrointestinal safety of flurbiprofen.
• GCS demonstrates potential for enhancing the delivery of poorly water-soluble drugs.