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Development of a single unit extended release formulation for ZK 811 752, a weakly basic drug
H Kranz1, C Guthmann, T Wagner
1Pharmaceutical Development, Schering AG, D-13342 Berlin, Germany. Heiko.Kranz@schering.de
Summary
This study developed a pH-independent drug release matrix tablet for ZK 811 752, a treatment for autoimmune diseases. Organic acids were added to maintain a stable micro-environment, ensuring consistent drug dissolution regardless of external pH.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Materials Science
Background:
- ZK 811 752, a candidate for autoimmune disease treatment, exhibits pH-dependent solubility.
- Conventional matrix tablets show decreased drug release with increasing pH.
- This pH-dependency poses a challenge for consistent therapeutic efficacy.
Purpose of the Study:
- To develop a pH-independent drug release formulation for ZK 811 752.
- To overcome the limitations of pH-dependent solubility in matrix tablet formulations.
- To achieve consistent and predictable drug release profiles.
Main Methods:
- Investigated three matrix formers: polyvinylacetate/polyvinylpyrrolidone, ethylcellulose (EC), and hydroxypropyl methylcellulose (HPMC).
- Incorporated organic acids (fumaric, tartaric, adipic, glutaric, sorbic) into the drug-polymer system.
- Evaluated drug release from matrix tablets in a dissolution medium.
Main Results:
- Addition of organic acids successfully maintained low pH within the tablets.
- This maintained micro-environmental pH ensured consistent dissolution of the weakly basic drug.
- pH-independent drug release was achieved across different matrix formers.
Conclusions:
- An extended-release matrix tablet formulation for ZK 811 752 was successfully developed.
- The formulation incorporates drug, polymer, and organic acid to ensure pH-independent release.
- This approach offers a viable solution for delivering drugs with pH-dependent solubility.