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Enhancing and sustaining AMG 009 dissolution from a matrix tablet via microenvironmental pH modulation and
Mingda Bi1, Ali Kyad, Y-H Kiang
1Formulation Group, Pharmaceutical R&D, Amgen Inc., Thousand Oaks, California 91320, USA. mbi@amgen.com
AAPS Pharmscitech
|September 14, 2011
Summary
This study enhanced AMG 009 tablet dissolution using pH modifiers like sodium carbonate and nucleation inhibitors such as HPMC E5 LV, achieving a 17.5-fold increase in drug release via supersaturation.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Formulation Development
Background:
- Optimizing drug dissolution is critical for therapeutic efficacy.
- Supersaturation is a key strategy to enhance drug release.
- AMG 009 tablet dissolution requires improved strategies for enhanced bioavailability.
Purpose of the Study:
- To investigate the combined effects of pH modifiers and nucleation inhibitors on AMG 009 tablet dissolution.
- To enhance and sustain the dissolution of AMG 009 through supersaturation.
- To evaluate the impact of formulation excipients on AMG 009 release.
Main Methods:
- Formulation of AMG 009 tablets with various bases (pH modifiers) and polymers (nucleation inhibitors).
- Dissolution testing of formulated tablets under controlled conditions.
- Evaluation of excipient effects, including compression force and disintegrants.
Main Results:
- Sodium carbonate significantly enhanced AMG 009 dissolution.
- HPMC E5 LV effectively sustained AMG 009 supersaturation.
- Combined use of sodium carbonate and HPMC E5 LV resulted in a 17.5-fold increase in dissolution (4% to 70%).
- Compression force had no significant impact on AMG 009 release.
- Disintegrating agents decreased AMG 009 dissolution.
Conclusions:
- The combination of pH modifiers and nucleation inhibitors is highly effective for enhancing AMG 009 tablet dissolution.
- Sodium carbonate and HPMC E5 LV represent optimal choices for achieving supersaturation and sustained release of AMG 009.
- Formulation strategies involving supersaturation hold significant promise for improving AMG 009 bioavailability.
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