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Novel dissolution methods for drug release testing of Long-Acting injectables
Nilesh Malavia1, Quanying Bao1, Diane J Burgess1
1University of Connecticut, Department of Pharmaceutical Sciences, Storrs, CT 06269 USA.
International Journal of Pharmaceutics
|August 25, 2024
Summary
Novel adapters improve drug release testing for long-acting injectables, enabling reliable in vitro-in vivo correlations (IVIVCs) for sustained drug delivery systems. These adapters enhance reproducibility and discriminatory ability for parenteral products.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Analytical Chemistry
Background:
- Long-acting parenteral drug products require reliable in vitro release testing for development and generic approvals.
- Current methods for testing drug release from long-acting injectables exhibit high variability, poor reproducibility, and lack in vivo relevance.
- Existing methods are often unsuitable for developing in vitro-in vivo correlations (IVIVCs) due to short release durations.
Purpose of the Study:
- To develop and validate novel adapters for USP-type-II and IV dissolution apparatus to improve drug release testing of long-acting parenteral products.
- To assess the performance of these adapters in terms of reproducibility, variability, discriminatory ability, and release duration.
- To evaluate the suitability of adapter-based methods for developing in vitro-in vivo correlations (IVIVCs).
Main Methods:
- Development of three novel adapter designs: two open (conical, ellipsoidal) for USP-type-IV and one closed (conical) for USP-type-II apparatus.
- Validation using Depo Provera 150® (long-acting injectable suspension) and its Q1/Q2 equivalents.
- Assessment of risperidone in situ forming implants using the USP-type-II adapter.
Main Results:
- All three novel adapter designs successfully retained suspensions and implants, achieving release durations of 3-6 weeks and up to one month.
- Methods demonstrated good reproducibility (RSD≤5%), minimal variability, and strong discriminatory ability.
- A successful Level A IVIVC was established for Depo SubQ Provera 104® and its equivalents using USP-type-IV apparatus with a conical adapter.
Conclusions:
- The developed novel adapters significantly enhance the in vitro release testing of long-acting parenteral drug products, including suspensions and implants.
- Adapter-based dissolution methods are suitable for IVIVC development, addressing limitations of current testing protocols.
- These adapters offer a promising solution for the reliable in vitro release testing of diverse long-acting parenteral drug products.
Keywords:
In vitro release testing, USP apparatus type- II & IVLong-acting injectablesMedroxyprogesterone acetateNovel adaptersRisperidoneMore Related Videos
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