title: A study of critical functionality-related characteristics of HPMC for sustained-release tablets.
abstract: The drug release profile from hydrophilic matrix tablets can be crucially affected by the variability of physicochemical properties of the controlled release agent. This study investigates and seeks to understand the functionality-related characteristics (FRCs) of hydroxypropyl methylcellulose (HPMC) type 2208, K4M grade, that influence the release rate of the model drug carvedilol from hydrophilic matrix tablets during the entire dissolution profile. The following FRCs were examined: particle size distribution, degree of substitution, and viscosity. Eight different HPMC samples were used to create a suitable design space. Multiple linear regression (MLR) and partial least squares regression (PLSR) analyses were used to create models for each time point. The PLSR results show that the first part of the drug release profiles is mainly regulated by the HPMC particle size. Apparent viscosity and hydroxypropoxy content (%HP) become important in later stages of the drug release profile, when the influence of particle size distribution decreases. These findings make it possible to better understand the importance of FRCs. Larger HPMC particles increase drug release in the first part of the drug release profile, whereas decreased apparent viscosity and a higher degree of %HP increase the drug release rate in the later part of the drug release profile.
authors.affiliation: a KRKA , d. d., Novo Mesto , Slovenia.|b Faculty of Pharmacy , University of Ljubljana , Ljubljana , Slovenia.
authors.forename: Darjan
authors.initials: D
authors.lastname: Košir
authors.affiliation: a KRKA , d. d., Novo Mesto , Slovenia.
authors.forename: Tadej
authors.initials: T
authors.lastname: Ojsteršek
authors.affiliation: b Faculty of Pharmacy , University of Ljubljana , Ljubljana , Slovenia.
authors.forename: Saša
authors.initials: S
authors.lastname: Baumgartner
authors.affiliation: a KRKA , d. d., Novo Mesto , Slovenia.|b Faculty of Pharmacy , University of Ljubljana , Ljubljana , Slovenia.
authors.forename: Franc
authors.initials: F
authors.lastname: Vrečer
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D065546:Drug Liberation; D065347:Hypromellose Derivatives / Q000737:chemistry* / Q000493:pharmacokinetics*; D013607:Tablets
chemical_list: D003692:Delayed-Action Preparations; D013607:Tablets; D065347:Hypromellose Derivatives
keywords: HPMC matrix tablets; Quality by Design (QbD); drug dissolution rate; functionality-related characteristics (FRCs); multiple linear regression (MLR); partial least squares regression (PLSR)