Relationship between dissolution efficiency of Oxazepam/carrier blends and drug and carrier molecular descriptors using multivariate regression analysis.
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.
Cutrignelli
Annalisa
A
Dipartimento Farmaco-Chimico, Facoltà di Farmacia, Università degli Studi di Bari, Via Orabona 4, Bari, Italy.
Lopedota
Angela
A
Trapani
Adriana
A
Boghetich
Giancarlo
G
Franco
Massimo
M
Denora
Nunzio
N
Laquintana
Valentino
V
Trapani
Giuseppe
G
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
D004337:Drug Carriers; D013607:Tablets; D010076:Oxazepam