title: Modeling of latent structure of indomethacin solid dispersion tablet using Bayesian networks.
abstract: BACKGROUND
  When designing pharmaceutical products, the relationships between causal factors and pharmaceutical responses are intricate. A Bayesian network (BN) was used to clarify the latent structure underlying the causal factors and pharmaceutical responses of a tablet containing solid dispersion (SD) of indomethacin (IMC).
  
  
  METHODS
  IMC, a poorly water-soluble drug, was tested with polyvinylpyrrolidone as the carrier polymer. Tablets containing a SD or a physical mixture of IMC, different quantities of magnesium stearate, microcrystalline cellulose, and low-substituted hydroxypropyl cellulose, and subjected to different compression force were selected as the causal factors. The pharmaceutical responses were the dissolution properties and tensile strength before and after the accelerated test and a similarity factor, which was used as an index of the storage stability.
  
  
  RESULTS
  BN models were constructed based on three measurement criteria for the appropriateness of the graph structure. Of these, the BN model based on Akaike's information criterion was similar to the results for the analysis of variance. To quantitatively estimate the causal relationships underlying the latent structure in this system, conditional probability distributions were inferred from the BN model. The responses were accurately predicted using the BN model, as reflected in the high correlation coefficients in a leave-one-out cross-validation procedure.
  
  
  CONCLUSIONS
  The BN technique provides a better understanding of the latent structure underlying causal factors and responses.
authors.affiliation: Department of Pharmaceutics, Hoshi University, Ebara, Shinagawa-ku, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Shingo
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Kozo
authors.initials: K
authors.lastname: Takayama
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D001499:Bayes Theorem; D007213:Indomethacin / Q000737:chemistry*; D010316:Particle Size; D012995:Solubility; D013607:Tablets / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013607:Tablets; D007213:Indomethacin