(M1230-09-57) Optimization of Nifedipine Tablets with OROS Technology for Controlled Drug Release

Purpose: This study aims to develop and optimize nifedipine tablets utilizing OROS(ostmotic-controlled release oral delivery system) technology to achieve a sustained and controlled release of the drug over a 24-hour period, thereby enabling once-daily dosing and improving therapeutic efficacy.

Methods: Tablet Preparation: Core tablets were prepared by direct compression followed by coating with a semipermeable membrane using a pan coater. The components of the active pharmaceutical ingredient (API) layer and Push layer were mixed and processed via granulation. The resulting granules from both layers were compressed using a bilayer tablet press to obtain bilayer tablets. The compressed cores were subsequently coated with a cellulose acetate and polyethylene glycol solution in acetone, followed by drying under controlled conditions. A 0.9 mm diameter orifice was then precisely drilled on the drug layer side of each tablet using a laser drilling machine.

Results: Initial formulation exhibited two major defects: (1) film whitening, which impaired vision-based orifice drilling and led to non-orifice drug release; and (2) film edge cracking, compromising tablet integrity. Optimization of coating parameters—including reduced solid content, increased solvent ratio, adjusted inlet temperature, elevated flow rate, and increased weight gain—resulted in the resolution of both defects. Accurate orifice formation and controlled drug release via the orifice were achieved.

Conclusion: This study successfully demonstrated that coating-related defects such as whitening and edge cracking during OROS-based formulation of nifedipine tablets can be resolved by fine-tuning critical process parameters. The optimized formulation achieved enhanced film quality, reliable orifice-mediated release, and robust in vitro performance. The TEST formulation showed equivalent dissolution profiles to the reference standard (Adalat OROS) across multiple pH conditions, indicating its potential for bioequivalence and once-daily sustained therapeutic effect. The combination of 13% weight gain and 0.9 mm orifice diameter is considered the optimal condition for achieving desired controlled-release characteristics.

Figure 1. Resolution of formulation defects through coating process optimization


Figure 2. Comparative in vitro dissolution profiles of TEST formulation vs. Adalat OROS under various pH conditions.


Figure 3. Impact of weight gain and orifice diameter on drug release kinetics in pH 6.8 medium.