ABSTRACT
Objective To prepare dihydromyricetin (DMY) long-circulating liposomes and evaluate in vitro release dynamics and in vivo pharmacokinetics in rats. Methods Film-ultrasonic method was used to prepare DMY liposomes by single factor experiment and orthogonal test to optimize the formulation and preparation of DMY liposomes. The particle size and zeta potential of liposomes were determined by laser particle size analyzer. The morphological examination of liposomes was performed by using transmission electron microscopy. The liposome release in vitro was studied using dialysis method. DMY concentration in rat plasma was determined by the established LC-MS/MS method. Results The optimal prescription was 75∶20∶5 for soybean phospholipid-cholesterol-mPEG 2000-DSPE, and 1∶12 for DMY-lipid (wt/wt) with the ultrasonic time of 20 min and loading temperature of 60 ℃ in pH 5.0 PBS buffer. Under the optimized conditions, DMY liposomes was sphere with mean particle size of (117.9 ± 5.5) nm and mean zeta potential of (−2.6 ± 1.7) mV, the encapsulation efficiency and drug-loading content was (54.7 ± 3.3) % and (4.3 ± 0.2) %, respectively. The in vitro accumulative release rate of 48 h was 86% in pH 1.2 and pH 6.8 dissolve medium. Compared with free DMY, the t1/2z and AUC0-∞ of DMY liposome were increased by 2.7-fold and 1.8-fold, respectively. Conclusion Compared with free DMY, DMY liposomes released gently and slowly in vitro, eliminated slowly in vivo, and had higher bioavailability of oral administration.
ABSTRACT
Objective To prepare TOGA-X4 microparticles with uniform size and good rehydration property and to obtain the stable and reliable preparation process, and evaluate the in vitro release characteristics. Methods With the average particle size, polydispersity index and rehydration as indexes, optimizing the process of antitumor active substance TOGA-X4 microparticles by stainless steel rapid film emulsification method through single factor investigation to investigate the factors influencing the size and dispersion of the drug microparticles and observe the morphology of the particles by scanning electron microscopy. With the cumulative release degree of TOGA-X4 as index, direct drug release method was adopted to determine the cumulative release rate of TOGA-X4 and the size of TOGA-X4 microparticles. The curve of in vitro drug release was fitted with different release model to estimate the in vitro release characteristics of TOGA-X4 raw powders and TOGA-X4 microparticles. Results The optimized preparation technology contained TOGA-X4 mass concentration of 5 mg/mL in oil phase, PVA mass concentration of 30 mg/mL in for aqueous phase, the ratio of oil to water was 1:1, transmembrane pressure at 0.4 MPa, sucrose aqueous solution of 50 mg/mL as freeze-drying protective agent, curing temperature at 70 ℃; Compared with other in vitro release models, the logistic equation was the fittest model to TOGA-X4 microparticles, zero order equation was the fittest model to TOGA-X4. Conclusion The preparation of microparticles by stainless steel rapid film emulsification is simple, stable and reliable, which can improve the dissolution rate of insoluble drugs and has advantages in the preparation of microparticles of poorly water-soluble drugs.
ABSTRACT
Objective To optimize the preparation process of honokiol long-circulating liposomes (HLCL) and study the in vitro and in vivo release. Methods An orthogonal experiment was designed to optimize the composition of HLCL using entrapment efficiency as evaluation indicator. The liposome surface morphology was observed by transmission electron microscope (TEM), and the liposome release in vitro was studied by dialysis method. The concentration of honokiol in rat plasma was determined by the established LC-MS/MS method, and the differences in pharmacokinetic parameters were compared after honokiol and HLCL (20 mg/kg) were orally administered to SD male rats, respectively. Results The optimal composition of HLCL was 8:1:1 for soya phosphatidyl choline-cholesterol-mPEG2000-DSPE, and 1:10 for honokiol-liposome materials with the ultrasonic time of 12 min. Under the optimized conditions, HLCL was sphere with mean particle size of 121.5 nm and mean Zeta potential of -30.8 mV, the encapsulation efficiency and drug-loading content was 84.7% and 10.4%, respectively. In vitro release results showed that the liposomes could be gently and slowly release with the 24 h cumulative release rate at pH 1.2 and pH 6.9 dissolve medium of 80% and 71%, respectively. Based on the pharmacokinetic results, Cmax, tmax, and t1/2 were (23.29 ± 11.76) ng/mL, (0.13 ± 0.05) h and (10.59 ± 5.72) h for HLCL, and (79.34 ± 56.32) ng/mL, (0.30 ± 0.07) h and (4.44 ± 3.14) h for honokiol, respectively. There was no significant difference about the AUC0-∞ following oral administration of honokiol and HLCL at isodose honokiol (20 mg/kg). Conclusion Compared with honokiol, HLCL was released gently and slowly in vitro, absorpted rapidly and eliminated slowly in vivo.
ABSTRACT
OBJECTIVE: To study preparation technology and properties of a new kind of iron-supplement of alginate-iron (III) complex. METHODS: The preparation parameters of polysaccharide iron (III) complex with sodium alginate and ferric trichloride were optimized by means of the single factor and response surface design. Alginate-iron (III) complex was characterized by IR and DSC. Its reducibility and drug release percentage were determined in simulated gastrointestinal liquid. RESULTS: Optimum condition follows; alginate sodium to ferric trichloride with mass ratio of 1:3.2 and alginate sodium to sodium citrate with mass ratio of 1:1.4, which were reacted in pH 6.95 of reaction liquid and at 80℃ of water bath lasting for 3. 29 h and generated alginate-iron (III) complex with the 19.57% of iron content. The IR and DSC indicated that the hydroxyl groups of alginate was combined with Fe(III). The alginate-iron (III) complex could be dissolved and reduced easily by vitamin C in physiological pH conditions. And the cumulative release percentage was more than 80% within 60 min in stimulated gastrointestinal liquid. CONCLUSION: The preparation technology of alginate-iron (III) complex was feasible. The product is high iron content and the solubility. And it can meet with the fundamental functions as a new kind of is supplement source.
ABSTRACT
Objective: To prepare pH-dependent Paridis Rhizoma saponin (PRS) and Astragali Radix polysaccharide (ARP) colon targeting pellets for the treatment of colon cancer and finish its in vitro release performance evaluation. Methods: The colon targeted pellets were prepared with extrusion-spheronization and air-flow coating method and the the process parameters were optimized by orthogonal design. The coating fluid prescription was investigated by single factor test. In vitro release performance evaluation of the pellets was evaluated with polyphyllin I and II as the indexes. Results: The optimum technologic parameters of extrusion spheronization equipment were as follows: the rate of extrusion was 60 r/min, the rate of spheronization was 1 200 r/min, and the time of spheronization was 5 min. The optimum coating liquid formulation of pH-dependent colon targetting pellets was 15% weight gains of Eudrugit S100, 1.5% anti-plastering aid amount of Glycerin monostearate, and 5% plasticizer amount of TEC. In vitro release test showed that cumulative release rate of berberine hydrochloride was close to 0% in artificial gastric juice after 2 h and less than 10% in artificial intestinal fluid after 4 h, but the cumulative release rate in artificial colon juice after 2 h was more than 90%. Conclusion: The preparation method can be applied to the preparation of colon targeted pellets and the pellets can achieve the targeted release in the colon.
ABSTRACT
Objective To prepare paeoniflorin gastric floating tablets and to optimize the formulation.Methods Gastric floating tablets were prepared by wet granulation,with floating performance and in vitro cumulative release rate as evaluat indi-cators,single factor tests and orthogonal design test were adopted for the optimal formulation.Results With HPMC K4M 20% as reinforcing materials,NaHCO315% as gas agent,PVPP 7% as the release of accelerator,lactose as a filler,the ob-tained gastric floating tablet can immediately play bleaching,continued to float more than 12 hours,and the cumulative release rate was more than 90%.Conclusion The optimal formulation of paeconiflorin floating tablet has achieved a sustained and slow release request floating,the operability is good.
ABSTRACT
Objective: To prepare pueratin (PU)-effervescent osmotic pump (controlled release) tablets (EOPT) based on the stable and sustained drug release dynamics of effervescent, and to study their in vitro release mechanism. Methods: The EOPT cores were prepared using sodium hydrogen carbonate and citric acid as effervescent and polyethylene oxide N80 as suspending agent. The PU monolayer osmotic pump tablets were prepared using acetyl cellulose as coating, diethyl phthalate as plasticizer, and PEG 400 as porogen. The single-factor test was used to optimize the formulation depending on drug release. Results: The types and amounts of effervescent agent, suspending agent, osmotic promoter, and the weight of coating substance showed the significant influence on the cumulative release rate, while the amount of plasticizer in the coating, the release media, and the rotation rate had no significant effects on the drug release. The drug release model was fitting and the results of in vitro release model simulation showed a good reproducibility. Conclusion: A successful method for the preparation of PU-EOPT is developed. More than 85% of PU is released from PU-EOPT within 12 h in vitro (r > 0.999 0) following with zero-order release and the preparation process is simple.