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Formulation-dependent stability mechanisms affecting dissolution performance of directly compressed griseofulvin
Natalie Maclean1, Ibrahim Khadra2, James Mann3
1Centre for Continuous Manufacturing and Advanced Crystallisation (CMAC), University of Strathclyde, Glasgow, UK; Strathclyde Institute of Pharmacy & Biomedical Sciences, University of Strathclyde, Glasgow, UK.
International Journal of Pharmaceutics
|December 9, 2022
Summary
Drug formulation stability is crucial. This study found that griseofulvin dissolution rates decreased during storage, particularly with increased humidity, impacting drug bioavailability.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery
- Materials Science
Background:
- Drug product stability studies are essential for ensuring safety and efficacy during storage.
- Changes in dissolution performance can indicate alterations in bioavailability.
- Understanding formulation changes under stress conditions is key to robust drug development.
Purpose of the Study:
- To investigate the impact of accelerated storage conditions on the physical properties and dissolution rates of griseofulvin formulations.
- To correlate changes in dissolution with specific formulation components and storage humidity.
- To elucidate the mechanisms behind formulation instability during storage.
Main Methods:
- Preparation of three griseofulvin formulations using microcrystalline cellulose (MCC) with mannitol, lactose monohydrate, or dibasic calcium phosphate anhydrous (DCPA).
- Assessment of tensile strength, porosity, contact angle, disintegration time, and dissolution rate after storage under varied temperature and humidity.
- Analysis of physical property changes in relation to storage duration (1, 2, and 4 weeks).
Main Results:
- A decrease in dissolution rate was observed for all formulations post-storage.
- The extent of dissolution rate change strongly correlated with storage humidity.
- Formulation instability was linked to premature particle swelling (MCC/DCPA, MCC/lactose) or dissolution (MCC/mannitol).
Conclusions:
- Storage humidity is a critical factor influencing griseofulvin dissolution rate and formulation stability.
- The choice of excipient (mannitol, lactose, DCPA) significantly affects how formulations respond to storage conditions.
- Understanding these stability-controlling mechanisms is vital for developing reliable oral drug products.