Physicochemical characterization and dissolution enhancement of aceclofenac-hydroxypropyl beta-cyclodextrin binary...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems

Background:

• Aceclofenac (AC) is a non-steroidal anti-inflammatory drug with poor aqueous solubility, classifying it as Biopharmaceutics Classification System (BCS) Class II.
• Hydroxypropyl beta-cyclodextrin (HPbetaCD) is a cyclodextrin derivative known for its ability to form inclusion complexes with poorly soluble drugs, enhancing their physicochemical properties.

Purpose of the Study:

• To prepare and characterize binary systems of aceclofenac (AC) with hydroxypropyl beta-cyclodextrin (HPbetaCD) using various methods.
• To evaluate the impact of complexation on the in vitro dissolution rate and solubility of aceclofenac.
• To assess the potential of HPbetaCD complexation to improve the biopharmaceutical properties of aceclofenac.

Main Methods:

• Preparation of binary systems using cogrinding, kneading, and coevaporating methods, alongside a physical mixture for comparison.
• Characterization techniques included differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), mass spectroscopy, 1H nuclear magnetic resonance (NMR) spectroscopy, and scanning electron microscopy (SEM).
• In vitro dissolution studies were conducted to assess the drug release profiles of the prepared systems.

Main Results:

• 1H NMR studies confirmed the partial inclusion of aceclofenac within the HPbetaCD torus cavity, with a preference for the drug's phenyl ring.
• All prepared binary systems demonstrated superior dissolution rates and lower dose:solubility (D:S) ratios compared to pure aceclofenac.
• The kneaded binary system exhibited the most significant improvement, achieving complete aceclofenac release within 10 minutes and a D:S ratio of 5 mL.

Conclusions:

• Complexation of aceclofenac with HPbetaCD effectively enhances its dissolution rate and solubility.
• The kneading method proved most effective for forming aceclofenac-HPbetaCD inclusion complexes with improved drug release.
• This approach offers a promising strategy to potentially reclassify aceclofenac from BCS Class II to BCS Class I, improving its oral bioavailability without altering intrinsic permeability.