Development and evaluation of controlled-release bilayer tablets containing microencapsulated tramadol and acetaminophen

Purpose: To develop and characterize bilayer tablet formulations of tramadol HCl (TmH) and acetaminophen (AAP) microparticles.
Methods: Coacervation via temperature change was the encapsulated method used for the preparation of the microparticles, with ethyl cellulose (EC) of medium viscosity as the polymer for extending drug release. The microparticles of the two drugs were prepared separately and then compressed into bilayer tablets. The physicochemical compatibility and stability of the tablets were determined by Fourier transform infrared spectroscopy (FTIR), x-ray diffractometry (XRD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) while their mechanism and pattern of drug release were assessed by applying Higuchi, Zero order, First order and Korsmeyer-Peppas kinetic models. Bilayer tablets were subjected to accelerated stability studies for three months.
Results: FTIR, XRD, DSC and TGA data for the formulations indicate good compatibility and stability. Furthermore, accelerated stability studies confirmed the stability of the formulations. Controlled drug release from the microparticles and bilayer tablets was observed for 8 h and 12 h, respectively. The Higuchi model produced the best fit, with regard to release profile, for both drugs, with correlation coefficient (R ² ) of 0.966 and 0.960 for AAP and TmH, respectively.
Conclusion: Microencapsulated TmH and AAP can be developed into suitable bilayer tablets that are stable and capable of releasing the drugs over 12 h.

Keywords
Acetaminophen; Tramadol; Ethyl cellulose; Microparticles; Bilayer tablets; Kinetic models