Single Layer Extended Release Two-In-One Guaifenesin Matrix Tablet: Formulation Method, Optimization, Release Kinetics Evaluation and Its Comparison with Mucinex® Using Box-Behnken Design

Document Type: Research article

Authors

1 Department of Pharmaceutics, Faculty of pharmacy, Pharmaceutical Sciences Branch , Tehran, Islamic Azad University, Tehran-Iran (IAUPS)

2 Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907, United States

3 Tehran Chemie Pharmaceutical Company, Tehran, Iran

Abstract

Guaifenesin, a highly water-soluble active (50 mg/mL), classified as a BCS class I drug.
Owing to its poor flowability and compressibility, formulating tablets especially high-dose one,
may be a challenge. Direct compression may not be feasible. Bilayer tablet technology applied
to Mucinex®, endures challenges to deliver a robust formulation. To overcome challenges
involved in bilayer-tablet manufacturing and powder compressibility, an optimized single layer
tablet prepared by a binary mixture (Two-in-one), mimicking the dual drug release character of
Mucinex® was purposed.
A 3-factor, 3-level Box-Behnken design was applied to optimize seven considered dependent
variables (Release “%” in 1, 2, 4, 6, 8, 10 and 12 h) regarding different levels of independent
one (X1: Cetyl alcohol, X2: Starch 1500®, X3: HPMC K100M amounts). Two granule portions
were prepared using melt and wet granulations, blended together prior to compression. An
optimum formulation was obtained (X1: 37.10, X2: 2, X3: 42.49 mg). Desirability function was
0.616. F2 and f1 between release profiles of Mucinex® and the optimum formulation were 74
and 3, respectively. An n-value of about 0.5 for both optimum and Mucinex® formulations
showed diffusion (Fickian) control mechanism. However, HPMC K100M rise in 70 mg
accompanied cetyl alcohol rise in 60 mg led to first order kinetic (n = 0.6962). The K values
of 1.56 represented an identical burst drug releases. Cetyl alcohol and starch 1500® modulated
guaifenesin release from HPMC K100M matrices, while due to their binding properties,
improved its poor flowability and compressibility, too.

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