pH Sensitive graft copolymers for zero order drug release: a mechanistic analysis

Area of Science:

• Polymer Chemistry
• Materials Science
• Pharmaceutical Sciences

Background:

• Development of advanced drug delivery systems is crucial for improving therapeutic efficacy and patient compliance.
• pH-responsive polymers offer potential for controlled drug release based on physiological conditions.
• Aliphatic polyesters with tunable properties are desirable for biomedical applications.

Purpose of the Study:

• To synthesize and characterize novel aliphatic polyester graft copolymers containing methacrylic acid (MAA).
• To investigate the pH-responsive swelling, erosion, and dissolution behavior of these polymers.
• To evaluate the potential of these polymers as matrices for controlled, once-daily release of drugs with varying solubilities.

Main Methods:

• Synthesis of aliphatic polyesters via polycondensation of diol, dicarboxylic acid, and glycidyl methacrylate.
• Grafting of methacrylic acid (MAA) onto the polyester backbone to form graft copolymers.
• Preparation of drug-loaded microparticles by spray-drying and subsequent tablet compression.
• In vitro drug release studies of Diltiazem hydrochloride (DH), Indomethacin (IM), and Verapamil hydrochloride (VH).

Main Results:

• Synthesized graft copolymers exhibited pH-dependent swelling and erosion/dissolution behavior, remaining collapsed at acidic pH and swelling/dissolving at near-neutral pH.
• Tablets formulated from spray-dried microparticles demonstrated constant rate drug release for DH, IM, and VH.
• Drug release mechanisms varied: diffusion for DH and erosion/dissolution for IM and VH, influenced by polymer composition and MAA content.
• Increased MAA content and graft frequency enhanced drug release rates.

Conclusions:

• Novel aliphatic polyester graft copolymers with tunable pH-responsive properties were successfully synthesized.
• These polymers serve as effective matrices for developing once-daily dosage forms for diverse drugs.
• The developed single-polymer matrix system is easily manufacturable and offers a versatile platform for controlled drug delivery.