Single Layer Extended Release Two-in-One Guaifenesin Matrix Tablet: Formulation Method, Optimization, Release...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Formulation Development

Background:

• Guaifenesin, a BCS Class I drug, presents formulation challenges due to poor flowability and compressibility, especially for high-dose tablets.
• Bilayer tablet technology, as used in Mucinex®, addresses these challenges but involves complex manufacturing.
• Optimizing single-layer tablet formulations is crucial for simpler and more robust drug delivery systems.

Purpose of the Study:

• To develop an optimized single-layer tablet formulation for guaifenesin that mimics the dual drug release of Mucinex®.
• To overcome the manufacturing challenges associated with bilayer tablets and improve powder compressibility.
• To investigate the impact of cetyl alcohol, Starch 1500®, and HPMC K100M on guaifenesin release and tablet properties.

Main Methods:

• A Box-Behnken design was employed to optimize seven dependent variables (drug release at various time points) based on three independent variables: cetyl alcohol, Starch 1500®, and HPMC K100M.
• Two granule portions were prepared using melt and wet granulation techniques, then blended for compression into single-layer tablets.
• The optimized formulation was characterized by its drug release profile, similarity factors (F2, f1), and drug release kinetics (n-value).

Main Results:

• An optimal formulation was identified with specific amounts of cetyl alcohol (37.10 mg), Starch 1500® (2 mg), and HPMC K100M (42.49 mg), achieving a desirability function of 0.616.
• The release profiles of the optimized formulation showed high similarity to Mucinex® (F2=74, f1=3).
• Drug release was primarily controlled by Fickian diffusion (n≈0.5), with some formulations exhibiting first-order kinetics (n=0.6962) and burst release (K=1.56).

Conclusions:

• The optimized single-layer tablet formulation effectively mimics the release characteristics of Mucinex®.
• Cetyl alcohol and Starch 1500® successfully modulated guaifenesin release and improved the flowability and compressibility of the powder.
• This binary mixture approach offers a viable alternative to bilayer technology for formulating challenging drugs like guaifenesin.