Reducing burst release and enhancing sustained release in SAIB-based implants: The role of polyphenol-modification

Area of Science:

• Materials Science
• Pharmaceutical Sciences
• Drug Delivery

Background:

• Sucrose acetate isobutyrate (SAIB)-based in situ forming implants (SADS) offer potential for long-acting drug delivery.
• A significant challenge with SADS is the undesirable burst release of the active pharmaceutical ingredient (API).

Purpose of the Study:

• To develop a molecular-level strategy to mitigate burst release from SAIB implants.
• To covalently modify the antipsychotic drug aripiprazole (ARP) with specific polyphenols to enhance drug-matrix interactions.

Main Methods:

• Covalent modification of aripiprazole (ARP) with 4-hydroxybenzoic acid (HBA), protocatechuic acid (PCA), and gallic acid (GA).
• Fabrication and in vitro release studies of SAIB-based implants containing modified ARP.
• In vivo pharmacokinetic studies in rats to evaluate drug circulation and release profiles.
• Rheological and porosity analyses to elucidate the drug retention mechanism.

Main Results:

• ARP modified with gallic acid (ARP-GA) demonstrated a significant reduction in burst release (8.99%) compared to unmodified ARP (22.84%).
• ARP-GA implants exhibited sustained drug release over 30 days in vitro.
• In vivo studies showed a 2.5-fold increase in AUC, extended Tmax, and lower Cmax/CS for ARP-GA, indicating improved release control.
• Hydrogen bonding between polyphenol moieties and SAIB was identified as the mechanism for enhanced drug retention.

Conclusions:

• Polyphenol modification of APIs is a viable drug-centric approach to regulate burst release in SAIB-based long-acting injectable systems.
• This strategy significantly improves the safety and efficacy of SAIB-based delivery systems.
• The approach demonstrated broad applicability, proving effective for six additional drugs.