Solid-state dependent dissolution and oral bioavailability of piroxicam in rats

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Pharmacokinetics

Background:

• Piroxicam is a poorly water-soluble non-steroidal anti-inflammatory drug (NSAID).
• The solid-state properties of a drug significantly influence its dissolution rate and oral bioavailability.
• Understanding these effects is crucial for optimizing drug formulation and therapeutic efficacy.

Purpose of the Study:

• To investigate the impact of different solid-state forms of piroxicam on its dissolution and oral bioavailability in rats.
• To evaluate the effect of a novel polymeric excipient, Soluplus®, on piroxicam's oral absorption.
• To establish the correlation between solid-state characteristics and in vivo drug performance.

Main Methods:

• Comparison of dissolution profiles for piroxicam anhydrate I (AH), monohydrate (MH), and amorphous form in solid dispersion (SD).
• In vivo pharmacokinetic studies in rats to determine oral bioavailability of different piroxicam solid-state forms.
• Assessment of Soluplus®'s influence on piroxicam dissolution and bioavailability.

Main Results:

• Significant differences in dissolution rates and oral bioavailability were observed among the piroxicam solid-state forms.
• Amorphous piroxicam in SD exhibited the fastest in vitro dissolution, despite a solid-state transformation to MH in the dissolution medium.
• SD formulation resulted in the highest rate and extent of oral absorption in rats, followed by AH and MH.
• Soluplus® significantly enhanced both the dissolution and oral bioavailability of piroxicam.

Conclusions:

• The solid-state form of piroxicam critically affects its dissolution and oral bioavailability.
• Amorphous piroxicam formulated in solid dispersion with Soluplus® offers a promising approach to improve the oral absorption of this poorly water-soluble drug.
• Rational selection of solid-state forms and excipients is essential for developing effective piroxicam formulations.