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

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 appliedto Mucinex®, endures challenges to deliver a robust formulation. To overcome challengesinvolved in bilayer-tablet manufacturing and powder compressibility, an optimized single layertablet prepared by a binary mixture (Two-in-one), mimicking the dual drug release character ofMucinex® was purposed.A 3-factor, 3-level Box-Behnken design was applied to optimize seven considered dependentvariables (Release “%" in 1, 2, 4, 6, 8, 10 and 12 h) regarding different levels of independentone (X1: Cetyl alcohol, X2: Starch 1500®, X3: HPMC K100M amounts). Two granule portionswere prepared using melt and wet granulations, blended together prior to compression. Anoptimum formulation was obtained (X1: 37.10, X2: 2, X3: 42.49 mg). Desirability function was0.616. F2 and f1 between release profiles of Mucinex® and the optimum formulation were 74and 3, respectively. An n-value of about 0.5 for both optimum and Mucinex® formulationsshowed diffusion (Fickian) control mechanism. However, HPMC K100M rise in 70 mgaccompanied cetyl alcohol rise in 60 mg led to first order kinetic (n = 0.6962). The K valuesof 1.56 represented an identical burst drug releases. Cetyl alcohol and starch 1500® modulatedguaifenesin release from HPMC K100M matrices, while due to their binding properties,improved its poor flowability and compressibility, too.