title: Predictive evaluation of pharmaceutical properties of direct compression tablets containing theophylline anhydrate during storage at high humidity by near-infrared spectroscopy.
abstract: BACKGROUND
  Theophylline anhydrate (TA) in tablet formulation is transformed into monohydrate (TH) at high humidity and the phase transformation affected dissolution behavior.
  
  
  OBJECTIVE
  Near-infrared spectroscopic (NIR) method is applied to predict the change of pharmaceutical properties of TA tablets during storage at high humidity.
  
  
  METHODS
  The tablet formulation containing TA, lactose, crystalline cellulose and magnesium stearate was compressed at 4.8 kN. Pharmaceutical properties of TA tables were measured by NIR, X-ray diffraction analysis, dissolution test and tablet hardness.
  
  
  RESULTS
  TA tablet was almost 100% transformed into TH after 24 hours at RH 96%. The pharmaceutical properties of TA tablets, such as tablet hardness, 20 min dissolution amount (D20) and increase of tablet weight (TW), changed with the degree of hydration. Calibration models for TW, tablet hardness and D20 to predict the pharmaceutical properties at high-humidity conditions were developed on the basis of the NIR spectra by partial least squares regression analysis. The relationships between predicted and actual measured values for TW, tablet hardness and D20 had straight lines, respectively.
  
  
  CONCLUSIONS
  From the results of NIR-chemometrics, it was confirmed that these predicted models had high accuracy to monitor the tablet properties during storage at high humidity.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tokushima University, Tokushima, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Otsuka
authors.affiliation: Faculty of Sciences and Engineering, Konan University, Kobe, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Institute of Health Biosciences, Tokushima University, Tokushima, Japan.
authors.forename: Hideji
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsuka
mesh_terms: D019245:Compressive Strength; D004339:Drug Compounding / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D065546:Drug Liberation; D004355:Drug Stability; D004356:Drug Storage / Q000379:methods; D055119:Elastic Modulus; D006244:Hardness; D006813:Humidity; D044367:Phase Transition; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013607:Tablets / Q000032:analysis* / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods; D013806:Theophylline / Q000032:analysis / Q000737:chemistry*
chemical_list: D013607:Tablets; D013806:Theophylline
keywords: Storage at high humidity; chemometrics; dissolution test; hygroscopicity; polymorphic transformation; tablet formulation study; tablet hardness; theophylline anhydrate