Development of terfenadine-pseudoephedrine double-layer tablet dissolution-equivalent to core tablet

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Formulation Development

Background:

• Sustained-release formulations aim to improve drug efficacy and patient compliance.
• Terfenadine-pseudoephedrine combination therapy requires careful control of drug release profiles.
• Developing dissolution-equivalent generic formulations is crucial for therapeutic interchangeability.

Purpose of the Study:

• To design and evaluate a double-layer tablet as a dissolution-equivalent alternative to a terfenadine-pseudoephedrine core tablet.
• To optimize the composition of fast-release and sustained-release layers for bioequivalence.
• To confirm the dissolution profile similarity between the novel double-layer tablet and the core tablet.

Main Methods:

• Formulation of fast-release layer using various disintegrants and polymers.
• Preparation of sustained-release layer with controlled ratios of ethylcellulose and hydroxypropylmethylcellulose (HPMC).
• In vitro dissolution testing at different pH values (1.2, 4.0, 6.8) and analysis of drug release kinetics (Fickian diffusion).

Main Results:

• The optimized fast-release layer contained terfenadine/pseudoephedrine/lactose/cornstarch/sodium bicarbonate/hydroxypropylcellulose (HPC)/sodium lauryl sulfate/microcrystalline cellulose.
• The selected sustained-release layer composed of pseudoephedrine/ethylcellulose/HPMC exhibited comparable pseudoephedrine dissolution to the core tablet's inner layer.
• Dissolved drug amounts from the double-layer and core tablets showed less than 5% deviation, with no significant differences across tested pH levels.

Conclusions:

• The developed double-layer tablet formulation is dissolution-equivalent to the original terfenadine-pseudoephedrine core tablet.
• This formulation offers a viable alternative for achieving sustained drug release and therapeutic equivalence.
• The Fickian diffusion mechanism governs pseudoephedrine release from the sustained-release layer.