title: Relationship between dissolution efficiency of Oxazepam/carrier blends and drug and carrier molecular descriptors using multivariate regression analysis.
abstract: Quantitative structure-property relationships were developed for predicting the enhancement of dissolution rate of the model lipophilic drug Oxazepam (Oxa) from blends (BLs) with 12 structurally different carriers at three different drug/carrier weight ratios (1/5, 1/10, and 1/20). To this end, 36 BLs were prepared by the solvent-evaporation method and characterized by spectroscopic (FT-IR), thermoanalytical (DSC) and X-ray diffraction studies. The dissolution rate of the examined systems was quantified by logDE/DE(Oxa), where DE and DE(Oxa) are the dissolution efficiencies of the BL and pure drug, respectively. Twenty molecular descriptors, including parameters for size, lipophilicity, cohesive energy density (CED), and hydrogen bonding capacity were calculated and together with the experimental melting point (MP), were used in multivariate analysis. Twelve pertinent variables were detected after looking at the results of principal component analysis (PCA) and cluster analysis, and reliable six-descriptor models generated by Partial Least Squares-Projection to Latent Structures (PLS) method. Satisfactory coefficient of determination values were obtained (i.e., R(2) equal to 0.794 and Q(2) equal to 0.705). The equations generated can predict with reasonable accuracy the dissolution rate increase of the model lipophilic drug/carrier BLs.
authors.affiliation: Dipartimento Farmaco-Chimico, Facoltà di Farmacia, Università degli Studi di Bari, Via Orabona 4, Bari, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Cutrignelli
authors.forename: Angela
authors.initials: A
authors.lastname: Lopedota
authors.forename: Adriana
authors.initials: A
authors.lastname: Trapani
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Boghetich
authors.forename: Massimo
authors.initials: M
authors.lastname: Franco
authors.forename: Nunzio
authors.initials: N
authors.lastname: Denora
authors.forename: Valentino
authors.initials: V
authors.lastname: Laquintana
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Trapani
mesh_terms: D000704:Analysis of Variance; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D015233:Models, Statistical; D010076:Oxazepam / Q000008:administration & dosage* / Q000737:chemistry*; D012044:Regression Analysis; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013607:Tablets; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D013607:Tablets; D010076:Oxazepam