Minimization of Acid-Catalyzed Degradation in KinetiSol Processing through HPMCAS Neutralization.

Area of Science:

• Pharmaceutical Sciences
• Polymer Chemistry
• Drug Delivery

Background:

• Hypromellose acetate succinate (HPMCAS) is an enteric polymer used in amorphous solid dispersions (ASDs).
• Its acidic groups can cause drug degradation, limiting its use with acid-sensitive compounds.
• Pre-ionization of enteric polymers is a strategy to mitigate acid-mediated drug degradation.

Purpose of the Study:

• To evaluate the use of a pre-ionized enteric polymer (HPMCAS-Na) in solvent-free KinetiSol processing.
• To reduce acid- or base-mediated drug degradation during the formulation of amorphous solid dispersions.
• To assess the impact of pre-ionization on drug stability in KinetiSol solid dispersions (KSDs).

Main Methods:

• Pre-ionization of HPMCAS was achieved by reacting it with sodium carbonate solution.
• The ionized polymer (HPMCAS-Na) was thoroughly dried before use.
• Tetrabenazine (TBZ), a drug susceptible to acid/base degradation, was used as a model compound.
• KinetiSol solid dispersions (KSDs) were prepared using both untreated HPMCAS and HPMCAS-Na.

Main Results:

• Formulation of TBZ KSDs with HPMCAS-Na led to a 6- to 8-fold reduction in impurities.
• The reduction in impurities was observed for both acid- and base-catalyzed degradation products.
• HPMCAS-Na effectively minimized drug degradation during KinetiSol processing.

Conclusions:

• Pre-ionization of HPMCAS is a viable strategy to enhance drug stability in ASDs.
• This method is effective for solvent-free processing techniques like KinetiSol.
• Using HPMCAS-Na can significantly improve the quality and stability of drug products sensitive to pH-mediated degradation.