Investigation of Host-Guest Inclusion Complexes Between Carmustine and α-Cyclodextrin: Synthesis, Characterization,...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Materials Science

Background:

• Carmustine (BCNU) is a key chemotherapeutic agent for brain tumors.
• BCNU's clinical use is limited by poor solubility, stability, and rapid degradation.
• Developing stable BCNU formulations is crucial for enhanced therapeutic efficacy.

Purpose of the Study:

• To synthesize and characterize alpha-cyclodextrin (α-CD) inclusion complexes (ICs) with BCNU.
• To evaluate the impact of different synthesis methods (co-grinding, cryomilling, co-precipitation) on complexation.
• To assess the physicochemical properties and in vitro drug release of BCNU-α-CD ICs.

Main Methods:

• Synthesis of BCNU-α-CD ICs using co-grinding, cryomilling, and co-precipitation.
• Structural elucidation via 1H NMR, FT-IR, UV-Vis, 13C CP MAS NMR, and ESI-MS.
• Solubility studies using Job's continuous variation and Benesi-Hildebrand methods.
• In vitro drug release studies at various pH levels (4, 5, 6.5, 7.4).

Main Results:

• Co-precipitation demonstrated superior complexation efficiency, inclusion ratios, and drug-loading capacity.
• Complete inclusion of BCNU within α-CD was achieved with cryomilling and co-precipitation.
• A 1:1 host-guest stoichiometry was confirmed for the BCNU-α-CD complexes.
• Drug release followed Fickian diffusion, with higher release rates observed in acidic conditions.

Conclusions:

• Alpha-cyclodextrin effectively encapsulates BCNU, improving its physicochemical properties.
• The developed BCNU-α-CD ICs show potential for enhanced stability and solubility.
• This formulation strategy may improve BCNU's therapeutic effectiveness against brain tumors.