Dissolution kinetics of glibenclamide glass

Area of Science:

• Pharmaceutical Sciences
• Physical Chemistry

Background:

• Glibenclamide is a widely used antidiabetic drug.
• Understanding the dissolution kinetics of different glibenclamide forms is crucial for optimizing drug delivery and bioavailability.
• Polymorphism significantly impacts drug solubility and dissolution rates.

Purpose of the Study:

• To investigate and compare the dissolution kinetics of glibenclamide crystalline form I and glassy form II.
• To determine the influence of pH, stirring rate, and temperature on the dissolution profiles of both forms.
• To assess the stability of glibenclamide glassy form II and its transformation into crystalline form I under various storage conditions.

Main Methods:

• Determination of pH-solubility profiles for glibenclamide forms I and II.
• In vitro dissolution studies conducted at varying stirring rates, temperatures, and pH values.
• Analysis of dissolution data using Noyes and Whitney and Levich equations.
• Calculation of the heat of dissolution (Ea) for both forms.
• Monitoring of glibenclamide form II transformation into form I after storage at different temperatures.

Main Results:

• Glibenclamide glassy form II exhibited significantly higher solubility and dissolution rates compared to crystalline form I across all tested pH values.
• A notable increase in solubility and dissolution for form II was observed at pH 6.
• Dissolution kinetics were confirmed to be diffusion-controlled and zero-order, adhering to established physical chemistry models.
• The activation energy (Ea) for dissolution was found to be nearly identical for both forms.
• Storage of form II at elevated temperatures led to partial transformation into form I, with increased transformation correlating to higher storage temperatures and reduced dissolution rates.

Conclusions:

• Glibenclamide glassy form II offers superior dissolution properties over crystalline form I.
• The dissolution process for both forms is primarily diffusion-controlled.
• Glibenclamide glassy form II exhibits limited thermal stability, undergoing transformation to the less soluble crystalline form I upon storage at higher temperatures.
• These findings have significant implications for glibenclamide formulation development, highlighting the need to control storage conditions to maintain the desired amorphous state.