(584aa) Characterization of Hypromellose 2208 Properties Impacting Drug Delivery Kinetics of a Hydrophilic Matrix Tablet | AIChE

(584aa) Characterization of Hypromellose 2208 Properties Impacting Drug Delivery Kinetics of a Hydrophilic Matrix Tablet

Authors 

Rogers,, T. - Presenter, The Dow Chemical Co.
Zhao, J., The Dow Chemical Co.
Adden, R., The Dow Chemical Co.
Theuerkauf, J., The Dow Chemical Co.
Li, Y., The Dow Chemical Co.
Petermann, O., Dow Wolf Cellulosics GMBH & CO. OHG
Knarr, M., Dow Wolf Cellulosics GMBH & CO. OHG
Meunier, D., The Dow Chemical Co



The purpose of this work is to characterize the key properties of hypromellose 2208 impacting drug release kinetics from a hydrophilic matrix tablet.

Hypromellose (HPMC) from more than thirty HPMC K4M batches was used to formulate matrix tablets containing paracetamol or indapamide.  Formulations containing HPMC, API and all fillers and additives were either directly compressed or wet-granulated. Tablets were compressed using a Manesty Beta or Piccola rotary press. Tablet properties and dissolution testing were conducted according to USP methods. Each HPMC batch was assayed using harmonized pharmacopeial methodology. Furthermore, molecular weight distributions were characterized using size-exclusion chromatography (SEC).  

The Korsmeyer-Peppas power law equation (equation 1) and Peppas-Sahlin heuristic model (equation 2) below were used to fit the dissolution profiles. 

Mt/ M = ktn                                                                                                                      (1)

Mt/ M = kdt0.45+ krt0.89                                                                                                 (2)

Here, Mt/ Mdenotes fractional drug release at time t.  The constant, k, is a kinetic constant that measures the drug release rate while n is a diffusional exponent that depends on the release mechanism and the geometry of the tested matrix system.  The first term of equation (2) represents the Fickian diffusional contribution and the second term is the Case II or the relaxational contribution.  Polymer molecular weight and chain overlap concentration, C*, were obtained via SEC.  The viscosity of 2 wt % HPMC in water at 20 °C was predominately impacted by molecular weight and hydroxypropyl substitution level. Correlations were found between Mt, n, k, and C*.  According to Peppas et al., the power law can be seen as superposition of two mechanisms of drug transport, Fickian diffusion and case-II transport.  The exponent, n, varied between 0.53 and 0.68, indicating anomalous transport mechanism.  In this study, Mt varied with C* up to t=2 hr.  Mt appeared independent of C* at t > 4 hn was found initially increased with increasing C*, but subsequently decreased with further increase in C*.    

Chain overlap concentration was used to correlate with modified release performance for the presented HPMC matrix. This modeling strategy facilitates the optimization of sustained API release.