ABSTRACT
Objective: In order to improve the bioavailability of the insoluble drug silybin, silybin supersaturated self- nanoemulsifying drug delivery systems (SLB-S-SNEDDS) containing functional oil were prepared, its characterization and in vitro evaluation were also performed. Methods: Functional oils were screened by performing potassium ferrohydride reduction and 1,1- diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging experiments. The pseudo-ternary phase diagram was drawn to investigate the emulsifying ability of emulsifier. The proportion of mixed oil phase and drug loading capacity were explored by analyzing particle size, polydispersity index (PDI), zeta potential, etc. The type and concentration of supersaturated substance in SLB-S-SNEDDS were obtained by conducting the compatibility and dissolution experiments. SLB-S-SNEDDS was characterized with appearance, particle size distribution, self-emulsification efficiency, and morphology, and its in vitro dissolution, antioxidant capacity, and cytotoxicity were also evaluated. Results: The prescriptions of SLB-S-SNEDDS were as follows: (1) wheatgerm oil/Capryol 90- Cremophor ELP-Transcutol HP; (2) seabuckthorn seed oil/Capryol 90-Cremophor ELP-Transcutol HP. One g S-SNEDDS matrix contained 0.043 g of wheatgerm oil or sea-buckthorn seed oil, 0.387 g of Capryol 90, 0.380 g of Cremophor ELP, and 0.190 g of Transcutol HP. The adding amount of silybin in S-SNEDDS prescription was 20% of the sum of the equilibrium solubility of silybin in each component, and the adding amount of Soluplus was 0.1% of the total mass described above. The two obtained SLB-S-SNEDDS were transparent homogeneous liquid with light yellow (wheat germ oil) and bright yellow (seabuckthorn seed oil) color, respectively. After being dispersed, SLB-S-SNEDDS turned into subspherical white flat emulsion droplets with the particle size of about 50 nm, and the emulsification time was 65 s. Compared with raw materials and SLB-SNEDDS, the cumulative dissolution of silybin in SLB-S-SNEDDS was maintained between 85% and 110% within 8 h, indicating that the two systems can significantly improve the dissolution of silybin. The absorbance of SLB-S-SNEDDS after reaction with potassium ferricyanide (0.452-0.782, 0.488-0.765) and the DPPH free radical clearance of SLB-S-SNEDDS (39.09%-96.02%, 30.54%-89.20%) were all higher than those of raw silybin (0.411-0.760, 22.89%-63.21%), which suggested that the two systems can enhance the antioxidant capacity of silybin. Cytotoxicity test results showed that the cell survival rate in silybin raw material group, combination of silybin and S-SNEDDS group, and blank S-SNEDDS group were greater than 90% at 5 µmol/L and 10 µmol/L drug concentration, indicating that SLB-S-SNEDDS and its auxiliary materials were safe and less toxic to human cloned colorectal adenocarcinoma cell line (Caco-2). Conclusion: The SLB-S-SNEDDS containing functional oil prepared in this paper can not only increase the cumulative dissolution of silybin, but also enhance its antioxidant capacity, which provides a useful reference for supersaturated self-nanoemulsifying drug delivery systems (S-SNEDDS) to improve the water-solubility and bioactivity of insoluble drugs.
ABSTRACT
To prepare a new dosage form that can improve the drug loading of the film--ginkgolide B nanosuspension lyophilized powder orodispersible film(GB-NS-LP-ODF) and to evaluate its quality. Firstly, ginkgolide B nanosuspension(GB-NS) was prepared by media milling method, and then ginkgolide B nanosuspension lyophilized powder(GB-NS-LP) was prepared with freeze-drying method. The mannitol was used as lyoprotectant and its dosage was also investigated. GB-NS-LP-ODF was prepared by solvent casting method and its formulation was screened by single factor test method and optimized by orthogonal test. The appearance, mechanical properties, content uniformity and in vitro dissolution of the optimized GB-NS-LP-ODF were investigated. The particle size of prepared GB-NS was about 201 nm, and the optimal dosage of mannitol was 8%. According to the optimal formula, the GB-NS-LP-ODF was prepared with GB-NS-LP 35.6%, PVA 0588 49.4%, PEG 400 10.7% and CMS-Na 4.3%, and completely disintegrated in about 30 s, and the particle size of reconstituted GB nanoparticles from ODF was about 210 nm. The film with smooth appearance and good mechanical properties was stable within 30 days and the content uniformity(A+2.2 S<15) conformed to the regulations. Scanning electron microscope(SEM) showed that GB-NS-LP-ODFs were evenly distributed and the particle size was about 200 nm. X-rays diffraction(XRD) showed that its crystallinity was significantly lower than that of GB raw drug and GB-ODF. The results of in vitro release test showed that the drug film was completely dissoluted within 10 minutes. These results indicated that nanosuspension lyophilized powder was prepared by freeze drying of nanosuspensions, and then loaded into the orodispersible film to effectively increase the drug loading of the ODF and have broad application prospects.
Subject(s)
Ginkgolides , Lactones , Nanoparticles , Particle Size , Powders , Solubility , SuspensionsABSTRACT
Objective: To prepare the solid dispersion of rutin colloidal silicon dioxide (Ru-CSD-SD) and to promote the rutin oral absorption function, in order to evaluate its in vivo and in vitro oral absorption. Methods: Composition and method of Ru-CSD-SD were investigated by single factor test; Equilibrium solubility experiments, differential thermal analysis (DSC), and X-ray diffraction (XRD) were used to determine the Ru-CSD-SD. Cumulative dissolution rates and pharmacokinetic parameters of Ru-CSD-SD were evaluated by drug releasing in vitro and in vivo. Results: The preparation conditions of Ru-CSD-SD was selected on the basis of single factor test: Colloidal silicon dioxide AEROPERL® 300 pharma (CSD300) was used as carrier, the ratio of drug (rutin) and carrier (CSD300) was 1∶2, and the method was solvent evaporation. After preparation of Ru-CSD-SD, the equilibrium solubility of rutin increased by 2.7 times from 72.69 to 198.73 mg/L; The DSC and XRD were indicated that rutin existed in the solid dispersions at amorphous form. And cumulative dissolution rates of Ru-CSD-SD reached (82.01 ± 1.04)% in 5 min. After oral administration of rutin ordinary tablets and Ru-CSD-SD, t1/2 were 1.078, and 10.899 h, tmax were 1.5, and 0.5 h, and Ru-CSD-SD of Cmax (103.45 μg/mL) was 15.46 times of ordinary tablets (6.69 μg/mL). Ru-CSD-SD of AUC0-∞ (170.406 μg∙h/mL) was 12.20 times of ordinary tablets (13.965 μg∙h/mL). Conclusion: The Ru-CSD-SD with CSD300 can increase the solubility, dissolution rate, and bioavailability.
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Objective To optimize the preparation of liensinine HP-β-CD inclusion compound; To investigate its dissolution performance in vitro. Methods The inclusion compound of liensinine was prepared by using saturated water solution method; the cumulative dissolution (45 min) was used as an indicator and Box-Behnken design was adopted to evaluate the influence of feed ratio, mixing time and inclusion temperature on preparation process. Results were analyzed by multiple linear and binomial fitting; response surface methodology was used to screen the optimal inclusion process; predictive parsing and verification experiment were conducted; SEM, DSC, IR, and XRD were applied for the structural characterization of inclusion compound of liensinine. Results The optimal preparation process was: HP-β-CD was 4.5 times the amount of liensinine feeding amount; mixing time was 3.7 h; inclusion temperature was 52 ℃. HP-β-CD inclusion compound of liensinine formed. Conclusion Optimal inclusion process is stable and feasible, which can significantly improve the dissolution of liensinine and increase its bioavailability.
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Objective: To optimize the prescription of liensinine solid dispersion osmotic pump controlled release tablet and research its release characteristics in vitro. Methods: The cumulative release percent in 2, 6, and 12 h and the linear correlation coefficient of cumulative release curve were taken as evaluation indexes to select the optimal prescription by using the central composite design- response surface methodology (CCD-RSM). The main factors of influence on drug release, which were the dosage of NaCl and PEG 400, and coating agent thickness. Results: The optimal prescription for liensinine solid dispersion osmotic pump controlled release tablet were as follows: NaCl dose was 166.0 mg, PEG 400 content was 80.5%, and the coating weight gain was 3.5%. Conclusion: The prescription optimization model of liensinine solid dispersion osmotic pump controlled release tablet is optimized by CCD-RSM, and it is proved to follow zero-order release kinetics.