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Early development evaluation of AZD8081: a substrate for the NK receptors
K Sigfridsson1, M Ahlqvist, A Carlsson
1Pharmaceutical Development, AstraZeneca R&D Mölndal, Mölndal, Sweden. carl-gustav.sigfridsson@astrazeneca.com
Drug Development and Industrial Pharmacy
|March 23, 2011
Summary
AZD8081, a dual neurokinin (NK)1/2 receptor antagonist, is suitable for oral immediate release (IR) and extended release (ER) formulations. Highly crystalline Form B is recommended for development due to its stability.
Area of Science:
- Pharmaceutical Sciences
- Drug Development
- Formulation Science
Background:
- AZD8081 is a dual neurokinin (NK)1/2 receptor antagonist.
- Understanding its physicochemical properties is crucial for formulation development.
Purpose of the Study:
- To assess the suitability of AZD8081 for oral immediate release (IR) and extended release (ER) formulations.
- To identify optimal solid-state forms for pharmaceutical development.
Main Methods:
- Physicochemical characterization including solubility, pKa, and stability studies.
- Solid-state analysis of polymorphic forms (A and B).
- Stress testing of amorphous and crystalline material.
Main Results:
- AZD8081 exhibits low intrinsic solubility but improved solubility in simulated intestinal fluid.
- Chemical instability was observed in amorphous forms, while crystalline forms were stable.
- Crystalline AZD8081 exists as two polymorphs; Form B is more stable and less hygroscopic.
- AZD8081 demonstrated good stability in simulated intestinal and colon fluids.
Conclusions:
- Crystalline Form B of AZD8081 is the preferred form for development.
- AZD8081 is suitable for both IR and ER oral formulations.
- Impurity profile and solid-state form significantly impact AZD8081 stability.
