Risperidone solid dispersion for orally disintegrating tablet: its formulation design and non-destructive methods of evaluation.
The focus of present investigation was to assess the utility of non-destructive techniques in the evaluation of risperidone solid dispersions (SD) with methyl-β-cyclodextrin (MBCD) and subsequent incorporation of the SD into orally disintegrating tablets (ODT) for a faster release of risperidone. The SD was prepared by a solvent evaporation method and evaluated by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), near infrared spectroscopy (NIR), NIR-chemical imaging (NIR-CI), powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). DSC and XRD analysis indicated that crystallinity of SD has reduced significantly. FTIR showed no interaction between risperidone and MBCD. Partial least square (PLS) was applied to the NIR data for the construction of chemometric models to determine both components of the SD. Good correlations were obtained for calibration and prediction as indicated by correlation coefficients >0.9965. The model was more accurate and less biased in predicting the MBCD than risperidone as indicated by its lower mean accuracy and mean bias values. SD-3 (risperidone:MBCD, 1:3) was incorporated into ODT tablets containing diluent (D-mannitol, FlowLac(®) 100 or galenIQ™-721) and superdisintegrant (Kollidon(®) CL-SF, Ac-Di-Sol or sodium starch glycolate). Disintegration time, T(50) and T(90) were decreased in the formulations containing mannitol and Kollidon(®) CL-SF, but increased with galenIQ™-721 and sodium starch glycolate, respectively. NIR-CI images confirmed the homogeneity of SD and ODT formulations.
Rahman
Ziyaur
Z
Division of Product Quality and Research, Center of Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
Zidan
Ahmed S
AS
Khan
Mansoor A
MA
D000284:Administration, Oral; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D018967:Risperidone / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D019265:Spectroscopy, Near-Infrared; D013607:Tablets; D013678:Technology, Pharmaceutical; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry
D005079:Excipients; D013607:Tablets; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D018967:Risperidone