Non-destructive methods of characterization of risperidone solid lipid nanoparticles.

The objective of this investigation is to evaluate compositional variations and their interaction of the solid lipid nanoparticle (SLN) formulation of risperidone using response surface methodology of design of experiment (DOE) and subsequently, characterize the SLN by non-destructive methods of analysis. Box-Behnken DOE was constructed using drug (X(1)), lipid (X(2)) and surfactant (X(3)) level as independent factors. Compritol 888 ATO and sodium lauryl sulphate were used as lipid and surfactant, respectively. The SLN was prepared by solvent evaporation method and characterized by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), fourier infrared spectroscopy (FTIR), near infrared spectroscopy (NIR) and NIR-chemical imaging (NIR-CI). Responses measured were entrapment efficiency (Y(1)), D(90) (Y(2)), zeta potential (Y(3)), burst effect (Y(4)) and cumulative release in 8h (Y(5)). Statistically significant (p < 0.05) effect of X(1) on the Y(1), Y(2), Y(3) and Y(4) were seen. FTIR revealed no interaction between risperidone and compritol 888 ATO. TEM showed spherical and smooth surface SLN. Compritol retained its crystalline nature in the SLN formulation revealed by DSC and XRD studies. Homogenous distribution of risperidone and compritol 888 ATO was revealed by NIR-CI. Principal component analysis (PCA) and partial least square (PLS) were carried out on NIR data of SLN formulation. PLS showed correlation coefficient > 0.996 for prediction and calibration model of both risperidone and compritol 888 ATO. The accuracy of models in predicting risperidone and compritol 888 ATO were 1.60% and 11.27%, respectively. In conclusion, the DOE reveals significant effect of drug loading on SLN characteristics, and chemometric models based on NIR and NIR-CI data provided non-destructive method of estimation of components of SLN.

Rahman Z ，Zidan AS ，Khan MA 《-》

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 Z ，Zidan AS ，Khan MA 《-》

Crystallinity evaluation of tacrolimus solid dispersions by chemometric analysis.

Different destructive and nondestructive analytical methods, namely powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), Raman and near-infrared (NIR) spectroscopy and imaging, to detect and characterize tacrolimus trace crystallinity in an amorphous solid dispersion (SD) using chemometric analysis were developed. The SD was spiked with different percentages of the crystalline drug to construct an array of SDs with different crystallinity percentages. Partial least square (PLS) regression analysis was employed to compare the performance of the calibration models created using these analytical methods. The obtained results indicated a significant interaction between tacrolimus and the employed polymer and a drug dissolution dependency on the crystalline fraction within the SDs. Using two PLS factors, these analytical methods were ranked according to its specificity to detect the trace crystallinity of SDs as NIR>PXRD>Raman>DSC. Through the application of PLS, root-mean-squared error of calibration values of 2.91%, 5.36%, 7.07% and 11.58% were calculated for the calibration models constructed by NIR, PXRD, Raman and DSC, respectively. Having a prediction error of 2.1% and a correlation coefficient of 0.99, it is demonstrated that combined NIR imaging and chemometric analysis outperformed the other methods in detecting trace crystallinity in tacrolimus amorphous systems. The spatial distributions of amorphous and crystalline drug were also obtained in order to allow for studying the crystallization dissemination in the solid dispersions. Consequently, NIR and NIR imaging coupled with chemometry was shown to be a powerful tool for the prediction of drug crystallinity within SDs.

Zidan AS ，Rahman Z ，Sayeed V ，Raw A ，Yu L ，Khan MA ... -  《-》

In vitro characterization and invivo toxicity study of repaglinide loaded poly (methyl methacrylate) nanoparticles.

With the objective to achieve prolonged drug release, especially for the treatment of diabetes mellitus, and thereby to reduce the side effects of administration of conventional dosage form, repaglinide loaded PMMA nanoparticles have been formulated. These nanoparticles have been developed by solvent evaporation method and were subjected to various studies for characterization including photon correlation spectroscopy (PCS), scanning electron microscopy (SEM) and X-ray diffraction (XRD). These studies favorably revealed that the mean particle diameter of optimized formulation was 108.3nm and had spherical morphology with amorphous nature. Moreover, these particles were also subjected to Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) for compatibility analysis between drug and polymer. The results were positive and showed that, there were no interaction between drug and polymer. The optimized formulation demonstrated favorable in vitro prolonged release characteristics. Experimental in vitro release data were substituted with available mathematical models to establish the mechanism of release of repaglinide and was found to follow zero order, diffusion and erosion mechanisms. The in vivo toxicity study in albino rats showed no significant change in biochemical and pathological examinations. Hence, the designed system could possibly be advantageous in terms of prolonged release, to achieve reduced dose frequency and improve patient compliance of repaglinide.

Dhana Lekshmi UM ，Poovi G ，Kishore N ，Reddy PN ... -  《-》

Enhancement in antifungal activity of eugenol in immunosuppressed rats through lipid nanocarriers.

In the present study eugenol loaded solid lipid nanoparticles (SLN) was prepared and characterized for particle size, polydispersity index, zeta potential, encapsulation efficiency, in vitro release and in vivo antifungal activity. Effect of addition of liquid lipid (caprylic triglyceride) to solid lipid (stearic acid) on crystallinity of lipid matrix of SLN was determined by using Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) techniques. Transmission electron microscopy (TEM) was carried out to determine the morphology of SLN. In vivo antifungal activity of eugenol loaded lipid nanoparticles was evaluated by using a model of oral candidiasis in immunosuppressed rats. Particle size results showed that d(90) of SLN(1) (single lipid matrix) and SLN(2) (binary lipid matrix) was 332±14.2 nm and 87.8±3.8 nm, respectively. Polydispersity index was found to be in the range of 0.27-0.4 which indicate moderate size distribution. Encapsulation efficiency of SLN(2) (98.52%) was found to be more than that of SLN(1) (91.80%) at same lipid concentration (2%, w/v). Increasing of the solid lipid concentration from 2% (w/v) to 4% (w/v) resulted in increase in encapsulation efficiency and the particle size. SLN(2) shows faster release of eugenol than that of SLN(1) due to smaller size and presence of liquid lipid which provide less barriers to the diffusion of drug from matrix. TEM study reveals the spherical shape of SLN. FT-IR, DSC and XRD results indicate less crystallinity of SLN(2) than that of SLN(1). In vivo studies show no significant difference in log cfu value of all the groups at 0 day. At 8th day, log cfu value of group treated with saline (control), standard antifungal agent, eugenol solution, SLN(1) and SLN(2) was found to be 3.89±.032, 2.69, 3.39±.088, 3.19±.028 and 3.08±0.124, respectively. The in vivo study results indicate improvement in the antifungal activity of eugenol when administrated in the form of SLN.

Garg A ，Singh S 《-》