Development and evaluation of wafer loaded with sertaconazole solid dispersion for the treatment of oral candidiasis

Abstract Candidiasis is one of the most common fungal infections of oral cavity in humans, causing great oral discomfort, pain and aversion to food. To develop more effective antifungal systems for the treatment of oral candidiasis, an oral mucoadhesive wafer containing sertaconazole solid dispersion (STZ-SD) was developed in this study. Dispersion of STZ in Soluplus® as a solubility enhancement excipient was done by melting, solvent evaporation and freeze drying method at various STZ to Soluplus® ratios. The optimized STZ-SD was then incorporated in the sodium carboxymethyl cellulose (SCMC) gel, xanthan gum gel, or their combination to prepare the lyophilized wafers. The swelling capacity, porosity, and mechanical, release and mucoadhesive properties of the wafers, together with their antifungal activity, were then evaluated. The melting method sample with the ratio of 8:1 showed the best results in terms of saturation solubility and dissolution rate. The STZ-SD-composite wafer exhibited higher hardness and mucoadhesion, as compared to those made of the SCMC polymer. The STZ-SD-wafer also exhibited a greater antifungal effect when compared to the STZ-wafer. The present study, thus, suggested that the STZ-SD-wafer could serve as a novel effective delivery system for oral candidiasis treatment.

Optimization of preparation, characterization, and dissolution characteristics of lutein ester nanoparticles by anti-solvent method / 中草药

Objective To prepare lutein ester (LE) nanoparticles (LE-NPs) by anti-solvent method using tetrahydrofuran as solvent, deionized water as antisolvent and Poloxamer 188 as surfactant, and to optimize the process of getting LE-NPs. Methods The concentration of LE, ratio of solvent to solvent, type and dosage of surfactant, precipitation time and stirring speed were investigated factors affecting the particle size of LE-NPs. The raw LE and LE-NPs were observed and analyzed by scanning electron microscopy, laser particle size analyzer, X-ray diffraction, and differential scanning calorimetry; Solvent residue was tested by GC method. What’s more, the solubility and dissolving capability of raw LE and LE-NPs also were detected in vitro in this study. Results The optimized preparation conditions of LE-NPs were as follows: 10 min of stirring time, 50 mg/mL of LE concentration, 1∶7 of the volume ratio of solvent to antisolvent, 0.5% at mass fraction of poloxamer 188, 950 r/min of stirring speed, 25 ℃ of precipitation temperature. The mean particle size of spherical LE-NPs was 164 nm. XRD and DSC results showed that LE-NPs had lower crystallinity compared to raw drug, and mainly in amorphous state. The solvent residue result showed that tetrahydrofuran residue content in LE-NPs was 344.3 μg/g. Furthermore, the solubility and dissolution rate of LE-NPs were about 2.91 times and 9.65 times of raw LE. Conclusion LE-NPs prepared by antisolvent method could become a new formulation, which has higher solubility and bioavailability than raw LE.

Formulation of dried lignans nanosuspension with high redispersibility to enhance stability, dissolution, and oral bioavailability / 中国天然药物

Herpetospermum caudigerum lignans (HTL), one of the potential drugs with anti-hepatitis B virus and hepatoprotective effects, has limited clinical applications because of poor aqueous solubility and low bioavailability. Both herpetrione (HPE) and herpetin (HPN) are the most abundant ingredients in HTL and exhibit weak acidity. The purpose of the present study was to produce dried preparations of HTL (composed of HPE and HPN) nanosuspensions (HTL-NS) with high redispersibility using lyophilization technology. The HTL-NS was prepared by utilizing precipitation-combined homogenization technology based on acid-base neutralization reactions, and critical formulation and process parameters affecting the characteristics of HTL-NS were optimized. The resultant products were characterized by particle size analysis, SEM, XRD, stability, solubility, dissolution and in vivo bioavailability. HTL-NS showed near-spherical-shaped morphology and the size was 243 nm with a narrow PDI value of 0.187. The dried preparations with a relatively large particle size of 286 nm and a PDI of 0.215 were achieved by using 4% (W/V) mannitol as cryoprotectants, and had a better stability at 4 or 25 °C for 2 months, compared to HTL-NS. In the in vitro test, the dried preparations showed markedly increased solubility and dissolution velocity. Besides, in the in vivo evaluation, it exhibited significant increases in AUC, CMRT and a decrease in T, compared to the raw drug. In conclusion, our results provide a basis for the development of a drug delivery system for poorly water-soluble ingredients with pH-dependent solubility.

Preparation, optimization, and dissolution characteristics of curcumin nanoparticles lyophilized powder by antisolvent method / 中草药

Objective: Curcumin nanoparticles lyophilized powder (CNLP) were prepared by antisolvent method which was optimized using single factor method. In this process, acetone was used as solvent, deionized water was used as antisolvent, tween-80 was used as surfactant and mannitol was used as lyoprotectant. Methods: The main factors affecting the particle size of CNLP included the concentration of curcumin, volume ratio of solvent and antisolvent, dosage of surfactant, precipitation time, stirring speed, and dosage of lyoprotectant. The contrast experiments on dissolution in vitro was done between CNLP and raw curcumin powder. Results: The mean particle size of CNLP was (172.2 ± 4.6) nm; The Zeta potential of CNLP redissolving in water was (-19.7 ± 3.7) mV. The SEM graphs indicated the raw curcumin was in irregular and massive shape and its particle size was about 20 μm. The CNLP exhibited regular block structure and its particle size was about 170 nm which was obviously reduced compared with raw curcumin. The mean particle size of CNLP obtained from laser particle analyzer was in accord with the morphology of CNLP. The saturated solubility of CNLP was 41.32 times of raw curcumin powder in deionized water, 1.74 times in simulated gastric fluid and 4.11 times in simulated intestinal fluid through saturated solubility test, respectively. The dissolution rate of CNLP was 14.51 times of raw curcumin powder in water dissolution medium, 2.33 times in simulated gastric fluid and 44.79 times in simulated intestinal fluid through dissolution determination, respectively. Conclusion: The preparation process of CNLP using antisolvent method could improve the drawback of poor water solubility and enhance the bioavailability of curcumin.