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Quantitative determination of polymorphic impurity by X-ray powder diffractometry in an OROS formulation.
Mehdi Varasteh1, Zhengyu Deng, Helen Hwang
1ALZA Corporation, Department of Analytical Development, Mountain View, CA 94043, USA.
International Journal of Pharmaceutics
|October 9, 2008
Summary
The ALZA OROS drug delivery system with RWJ-333369 showed no polymorphic conversion during manufacturing. However, polymorph B impurity was detected in stability samples, indicating potential solid-state changes over time.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Solid-State Chemistry
Background:
- The ALZA OROS system aims to enhance drug load and reduce side effects for novel agents.
- RWJ-333369, a neuromodulatory agent, exhibits enantiotropic polymorphism with stable polymorph A at room temperature.
Purpose of the Study:
- To evaluate the polymorphic stability of RWJ-333369 within the ALZA OROS drug delivery system during manufacturing and stability testing.
- To establish a reliable analytical method for detecting polymorphic impurities.
Main Methods:
- Utilized X-ray Powder Diffractometry (XRD) as the preferred method for polymorphic analysis.
- Developed a quantitative XRD method using reference standards of polymorph A and B.
- Analyzed samples from manufacturing processes and accelerated stability studies at 60°C.
Main Results:
- No conversion of polymorph A to polymorph B was observed during the OROS RWJ-333369 manufacturing process.
- Polymorphic conversion of A to B was detected in stability samples stored at 60°C for two weeks.
- The developed XRD method had a detection limit of approximately 2% for polymorph B.
Conclusions:
- The ALZA OROS manufacturing process is robust against polymorphic conversion of RWJ-333369.
- Elevated temperatures can induce polymorphic instability in the OROS RWJ-333369 formulation.
- Further investigation into long-term stability under various conditions is warranted.
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