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Properties of enteric coated sodium valproate pellets
L Diane Bruce1, Hans-Ulrich Petereit, Thomas Beckert
1Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA. diane.bruce@quintiles.com
International Journal of Pharmaceutics
|September 16, 2003
Summary
Subcoat application and citric acid significantly impact enteric-coated sodium valproate dissolution. Citric acid enhances enteric coating but can reduce drug potency above 10% (w/w).
Area of Science:
- Pharmaceutical Technology
- Drug Delivery Systems
- Materials Science
Background:
- Enteric coatings are crucial for targeted drug release, protecting acid-labile drugs and preventing gastric irritation.
- Sodium valproate, an antiepileptic drug, requires controlled release to optimize therapeutic efficacy and minimize side effects.
- Understanding factors influencing enteric coating performance is essential for developing stable and effective drug formulations.
Purpose of the Study:
- To investigate the impact of subcoat application on the dissolution properties of enteric-coated sodium valproate pellets.
- To evaluate the role of micro-environmental pH, influenced by citric acid, on drug release characteristics.
- To determine the optimal conditions for enteric coating formulation and processing of sodium valproate pellets.
Main Methods:
- Preparation of sodium valproate pellets using solution-layering and wet-mass extrusion-spheronization techniques.
- Application of enteric coating (Eudragit L 30D-55) with varying weight gains.
- Incorporation of subcoats (Methocel-E5/HPMC, Opadry AMB) and citric acid into pellet formulations.
- Dissolution testing in 0.1N HCl to assess drug release profiles and USP enteric test compliance.
Main Results:
- Both solution-layered and wet-mass extruded pellets required specific weight gains of Eudragit L 30D-55 to meet USP enteric standards.
- Subcoat application (HPMC or Opadry AMB) and the presence of citric acid delayed sodium valproate release in acidic media.
- Citric acid improved enteric polymer film formation and coalescence, acting as a plasticizer.
- Drug release was dependent on citric acid levels and the resulting micro-environmental pH.
- Sodium valproate potency decreased significantly with >10% (w/w) citric acid due to conversion to valproic acid; potency was maintained with <10% (w/w) citric acid.
Conclusions:
- Subcoat application and citric acid content are critical parameters influencing the dissolution behavior of enteric-coated sodium valproate pellets.
- Citric acid can enhance enteric coating performance but requires careful control (<10% w/w) to prevent drug degradation.
- Optimized subcoat and citric acid levels are necessary for achieving desired drug release profiles and maintaining drug stability in enteric-coated formulations.