PVP solid dispersions containing Poloxamer 407 or TPGS for the improvement of ursolic acid release

Abstract Solid dispersions (SDs) of ursolic acid (UA) were developed using polyvinylpyrrolidone K30 (PVP K30) in combination with non-ionic surfactants, such as D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) or poloxamer 407 (P407) with the aim of enhancing solubility and in vitro release of the UA. SDs were investigated using a 24 full factorial design, subsequently the selected formulations were characterized for water solubility, X-ray diffractometry (XRD), differential scanning calorimetry (DSC), particle diameter, scanning electron microscopy, drug content, physical-chemical stability and in vitro release profile. SDs showed higher UA water-solubility than physical mixtures (PMs), which was attributed by transition of the drug from crystalline to amorphous or molecular state in the SDs, as indicated by XRD and DSC analyses. SD1 (with P407) and SD2 (with TPGS) were chosen for further investigation because they had higher drug load. SD1 proved to be more stable than SD2, revealing that P407 contributed to ensure the stability of the UA. Furthermore, SD1 and SD2 increased UA release by diffusion and swelling-controlled transport, following the Weibull model. Thus, solid dispersions obtained with PVP k-30 and P407 proved to be advantageous to enhance aqueous solubility and stability of UA.

Preparation and Quality Evaluation of Azelnidipine Enteric Solid Dispersion / 中国药房

OBJECTIVE：To prepare Azelnidipine enteric solid dispersion and evaluate its quality. METHODS ：Azelnidipine enteric solid dispersion was prepared by solvent method. Taking cumulative dissolution rate as the index ，single factor test was used to optimize carrier material type and its ratio. The quality of the product was evaluated by DSC ，XRD and FTIR ，and its stability was investigated. RESULTS ：After azelnidipine and carrier material of Eudragit L 100-55 acrylic resin were prepared to enteric solid dispersion at a ratio of 1∶5（m/m），its dissolution rate was significantly improved. DSC ，XRD and FTIR method had all verified the crystal form of azelnidipine changed and it existed in amorphous form. The results of stability test showed that Azelnidipine enteric solid dispersion was stable under high temperature （60 ℃），high humidity （75％）and strong light [ （4 500±500）lx] for 10 days. CONCLUSIONS ：Azelnidipine enteric solid dispersion by solvent method with Eudragit L 100-55 acrylic resin as carrier can eliminate the influence of crystal form ，improve dissolution and has good stability.

Improvement of in vitro dissolution and physical stability for spironolactone solid dispersion formulated with Soluplus / 药学学报

Spironolactone, a class II drug of the biopharmaceutics classification system, has low oral bioavailability due to poor solubility. Spironolactone solid dispersions were prepared using the solvent method in order to improve its aqueous solubility. Optimization studies of spironolactone solid dispersions were performed using in vitro dissolution tests. Differential scanning calorimetry, X-ray diffraction and Fourier transform infrared were used to investigate the physical state of the drug in carrier materials and to detect the possible interactions between the drug and carrier materials in the solid dispersions. In addition, stress tests were employed to elucidate the key factors which have influence on the stability of the spironolactone solid dispersions. Results showed that spironolactone in the solid dispersions formulated with Soluplus and HPMC-E5 were both in amorphous state and the hydrogen bonds between the drug and carrier materials were formed in the solid dispersion. Therefore, the in vitro dissolution of spironolactone was also significantly enhanced. Stress tests demonstrated that the physical stability of spironolactone solid dispersions prepared with Soluplus was greatly improved compared to those formulated with HPMC-E5. Thus, spironolactone solid dispersion formulated with Soluplus using the solvent method could be used to improve the in vitro dissolution and stability of poorly soluble drugs.

Study on preparation of quercetin solid dispersions and its bioavailability in rats / 中草药

Objective Quercetin solid dispersions (QSD) with hydrophilic carriers were prepared in order to enhance its dissolution rate and oral bioavailability in rats. Methods QSD with different ratios of polyvinylpyrrolidone (PVPK30), PEG6000, and xylitol were prepared by solvent method or melting-solvent method. Dissolution characteristics of QSD were evaluated and compared with that of the pure drug. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) were used to examine the crystallinity of solid dispersion, physical mixture, carriers and quercetin. Drug plasma concentrations were determined by high performance liquid chromatography mass spectrum (HPLC-MS) after oral administration in rats. Results The dissolution rate of quercetin from its solid dispersions was greatly enhanced. Dissolution percentages from the solid dispersion of quercentin-PVPK30-xylitol in 1:5:1 weight ratio were 40.63% and 68.58% at 5 min and 60 min respectively, while in the same time only 0.26% and 1.66% from pure quercetin. The results of DSC and XRPD demonstrated that quercetin was amorphously dispersed in solid dispersion. Oral bioavailability in rats of QSD was about 61-fold higher than that of pure drug. Conclusion QSD significantly improved quercetin dissolution rate and bioavailability in rat.

Preparation and in vivo and in vitro evaluation of Pulsatilla Saponin D Solid Dispersions / 中草药

Objective: To prepare the solid dispersion of Pulsatilla saponin D (PSD-SD) and evalution its in vivo and in vitro drug release behavior. Methods: The PSD-SD was prepared by solvent method. Three carriers were used in the PSD-SD. Infrared spectroscopy (IR), differential thermal analysis (DSC), and X-ray diffraction (XRD) were used to determine the PSD-SD. Dissolution rates and pharmacokinetic parameters were evaluated in vitro and in vivo characteristics of the PSD-SD. Results: When the PEG 6000 was used as carrier, the solubility of PSD was increased from 2.39 to 7.06 mg/mL, and the cumulative release rate of PSD reached 90% in 60 min, and the bioavailability of PSD was increased to 2.24 times. Conclusion: The solid dispersion prepared PSD can increase the solubility, dissolution rate, and bioavailability.

Preparation and characterization of micronized trans-cinnamic acid by anti-solvent crystallization method / 中草药

Objective: Using ethanol as solvent, deionized water as anti-solvent, and HPMC as the surfactant, to prepare trans-cinnamic acid (TCA) micro powder by single factor analysis. The effects of five experimental parameters on the mean particle size (MPS) and morphology of TCA nanosuspension were investigated. Methods: Transmission electron microscope (TEM), laser granulometric analysis, Fourier transform infrared spectroscopy (FTIR), high performance liquid chromatography-mass spectrometry (LC-MS), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and dissolution were used to analyze the characteristic of micronized TCA nanosuspension. Results: The micronized TCA with an MPS of 130 nm was obtained under the optimum conditions. The dissolution rate of TCA nanosuspension was 1.67 times of raw drug. Conclusion: Using anti-solvent recrystallization to prepare micronized TCA can improve the solubility and dispersion of TCA nanosuspension in water, and they provide the basis for further formulation development.

Studies on tanshinone IIA solid dispersion based on chitosan / 中草药

Objective: To prepare and characterize the solid dispersion of tanshinone IIA (Tan IIA) using chitosan (CS) and compare the dissolution of solid dispersion using CS with different molecular weight (MW). Methods: Tan IIA solid dispersion was prepared by the solvent method with CS as the carrier. The physical characteristics and in vitro dissolution of solid dispersion prepared by different MW of CS and different proportions of drug and carrier were further evaluated. Results: The ideal Tan IIA solid dispersion was prepared under the condition as follows: the weight ratio of Tan IIA-CS (MW 3 000-5 000) was 1:9. The in vitro dissolution of Tan IIA solid dispersion reached up to 90% at 60 min. The differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) demonstrated that Tan IIA existed as amorphous state in carriers. Conclusion: The results indicate that in vitro dissolution of Tan IIA is improved greatly by the solid dispersion with CS as the carrier. As a new type of solid dispersion carrier of Tan IIA, CS has its practical value.