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Related Experiment Videos

Study of tolbutamide-hydroxypropyl-gamma-cyclodextrin interaction in solution and solid state.

M D Veiga1, F Ahsan

  • 1Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Spain. mdveiga@eucmos.sim.ucm.es

Chemical & Pharmaceutical Bulletin
|June 24, 2000
PubMed
Summary

Tolbutamide-hydroxypropyl-gamma-cyclodextrin inclusion complexes significantly enhance tolbutamide solubility and dissolution. Solid-state complexation improved drug release compared to physical mixtures, indicating successful complex formation.

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Area of Science:

  • Pharmaceutical Sciences
  • Physical Chemistry

Background:

  • Tolbutamide (TBM) is an oral hypoglycemic agent with limited aqueous solubility.
  • Cyclodextrins, particularly hydroxypropyl-gamma-cyclodextrin (HPGCD), are known to improve the solubility and bioavailability of poorly soluble drugs.

Purpose of the Study:

  • To investigate the interaction between tolbutamide and hydroxypropyl-gamma-cyclodextrin in aqueous solution and solid state.
  • To evaluate the impact of complexation on tolbutamide's solubility and dissolution rate.

Main Methods:

  • Phase solubility studies in aqueous media.
  • Preparation of solid binary systems (physical mixtures and kneaded systems) at 1:1 and 1:2 molar ratios.
  • Characterization using hot-stage microscopy (HSM), differential scanning calorimetry (DSC), thermogravimetry (TG), and X-ray powder diffractometry (XRD).

Related Experiment Videos

  • Dissolution testing of pure tolbutamide, physical mixtures, and kneaded systems.

    • Main Results:

    • A soluble inclusion complex of tolbutamide-HPGCD was formed in aqueous solution, with an A(L) type phase solubility diagram.
    • Solid-state inclusion complexes were formed in both 1:1 and 1:2 kneaded systems.
    • The 1:2 kneaded system showed complete inclusion of tolbutamide within the HPGCD cavity.
    • Kneaded systems exhibited significantly improved drug dissolution compared to pure tolbutamide and physical mixtures.
    • No significant difference in dissolution profiles was observed between the 1:1 and 1:2 kneaded systems.

    Conclusions:

    • Tolbutamide-HPGCD inclusion complexes can be successfully formed in both aqueous solution and solid state.
    • Solid-state complexation via kneading significantly enhances the dissolution rate of tolbutamide.
    • HPGCD is an effective complexing agent for improving the pharmaceutical properties of tolbutamide.