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Objective: To prepare ligustrazine pamoate (Lig-PAM) sustained-release nanosuspension (Lig-PAM-NSps) and determine its in vitro release characteristics. Methods: Lig-PAM was prepared by hydrophobic salt formation method and its physicochemical properties were characterized. Then, Lig-PAM-NSps was prepared by miniaturized medium grinding method. The prescription and preparation process of Lig-PAM-NSps were optimized by the single factor and orthogonal experiment with average particle size, polydispersity index (PDI) and stability coefficient (SI) as indicators. Lig-PAM-NSps was characterized, and its stability and in vitro release was also investigated. Results: The compound ratio of Lig-PAM prepared by Lig and PAM in the amount of 1:1 was (97.48 ± 0.04)%. Compared with Lig, the solubilities of Lig-PAM in water and simulated body fluids were decreased by 95.50% and 77.39%, respectively. Fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffraction (XRD) showed that the Lig and PAM formed Lig-PAM. The optimum prescription size of Lig-PAM-NSps was (585 ± 5) nm, PDI was (0.328 ± 0.015) and SI was (0.928 ± 0.012). The scanning electron microscopy (SEM) showed that Lig-PAM-NSps was spherical with uniform size distribution, and the particle size was about 600 nm and its physical stability was good within 60 d. The results of in vitro release showed that Lig-PAM-NSps had obvious sustained-release effect compared with Lig solution within 48 h, and showed the first-order release characteristics [ln(1-Q) = 0.153 67 t + 80.458 14, r = 0.998 26]. Conclusion: The preparation progress of Lig-PAM-NSps is stable and can release Lig slowly in vitro.
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Objective: To prepare silymarin nanosuspension (SM-NS) with glycyrrhizic acid as stabilizer, and investigate the in vitro release characteristics and charge stabilization mechanism. Methods: SM-NS was prepared by high-speed shear-high pressure homogenization method. SM-NS lyophilized powder were prepared by freeze-drying method and characterized by physical and chemical characterization and in vitro release. The stability mechanism of SM-NS was studied from the ionic strength and pH value. Results: The dosage of glycyrrhizic acid (GA) was 0.15%. The preparation process was shear rate of 19 000 r/min, shear time of 4 min, homogenization pressure of 100 MPa, homogenization times of 12 times, and lyoprotectant was mannitol 3%, the average particle size of SM-NS lyophilized powder was (516.4 ± 10.4) nm, PDI was (0.260 ± 0.046); The in vitro release results showed that the dissolution rate and solubility of SM-NS lyophilized powder were significantly higher than the physical mixture; The study of charge stability mechanism showed that licorice acid can provide good charge stabilization and strong resistance to environmental impact. Conclusion: SM-NS is a potential and new nano-drug with high safety, which is formed by the charge stability of GA to significantly improve the solubility and stability of silymarin.
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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.
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Objective: To evaluate therelease characteristicsin vitro, pharmacokinetics in rabbits and in vivo-in vitro correlation of tectorigenin floating sustained-release tablets (TFSRT). Methods: The release characteristics of TFSRTin vitro was detected with HPLC in the artificial gastric fluid. Six Japanese Giant Ear Rabbits as self crossover control, which were given TFSRT and suspension liquid (200mg). The concentration of tectorigenin in plasma was determined with HPLC and the data were processed with PKsolver 2.0 software. Results:The cumulative releaserate of TFSRTin vitro was over 70% in 10 h.The pharmacokineticsin rabbits showed that TFSRT and tectorigenin suspension liquid conformed to the single compartment model and the pharmacokinetic parameters were obtained: tmax: (2.809±0.371) and (0.442±0.138)h, Cmax: (6.317±1.337) and (9.662±2.759) μg/mL, AUC0-t: (74.156±10.420) and (57.059±13.309) μg∙h/mL. The relative bioavailability of TFSRT was (134.63±27.94)%, so there was significant difference between them. Conclusion: TFSRT can release slowly, so it increase the relative bioavailability significantly. The correlation between the absorption in vivo and release in vitro is fine (r=0.9879), so the release rate in vitro can control the quality of TFSRT.
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Objective To prepare asiatic acid (AA) loaded chitosan-deoxycholic acid self-assembled micelles (AA-CS-DCA PMs) adopting chitosan-deoxycholic acid (CS-DCA) as carriers and investigate its pharmacokinetic characteristics in rats. Methods AA-CS-DCA PMs were prepared by ultrasonic dispersion method. The characteristics of micelles were evaluated by the distribution of particle size, Zeta potential, drug loading, encapsulation efficiency, and in vitro release. Model of bile drainage was established in conscious rats and pre-column derivatization HPLC method was used to determine the concentration of AA in bile. Moreover, the pharmacokinetics characteristics of AA-CS-DCA PMs in vivo was evaluated by tmax, Cmax and AUC0-t. Results The particle size was (70.5 ± 9.8) nm, the Zeta potential was (38.4 ± 0.8) mV, and encapsulation efficiency and drug loading were (77.8 ± 1.2)% and (11.7 ± 0.2)%, respectively. The in vitro release profile showed a sustained release property. In vivo study showed that Cmax of AA-CS-DCA group (26.05 ± 3.04) μg/h was 2.8 times higher than that of the control group (9.19 ± 1.12) μg/h; The tmax of AA-CS-DCA PMs group prolonged significantly (P < 0.05) in biliary excretion (2 h vs 1 h) and the elimination half-life t1/2 was 1.8 times of the control group [(2.68 ± 1.71) h vs (1.49 ± 0.38 h)]. In addition, the AUC0-24 h which reflected the degree of drug absorption increased by 200% compared with the control group [(99.05 ± 12.83) μg vs (33.56 ± 8.33) μg]. Conclusion The chitosan- deoxycholic acid self-assembled micelles can raise the concentration of AA and prolong the retention time in vivo, which effectively improve the oral bioavailability of AA.
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Objective: To determine the prescription technology of gastrodin starch microsphere and investigate its nasal mucoadhesion and in vitro release characteristics. Methods: Gastrodin starch microspheres were prepared by compound emulsion crosslinking method. According to the particle diameter, drug loading efficiency (DLE), and entrapment efficiency (EE), the best prescription technology was selected by using single-factor investigation and uniform design. Using toad palate mucosa as model and average residence time as indicator, mucoadhesion of gastrodin starch microsphere was evaluated. Using gastrodin API as a control, paddle method was applied to in vitro release test of gastrodin starch microspheres. The content of gastrodin was determined to calculate the cumulative release percentage. In addition, the curve of drug release in vitro was fitted with different release model to analyze the in vitro release characteristics of gastrodin starch microsphere in nasal cavity, synthetically. Results: The optimum prescription and preparation technology of gastrodin starch microsphere were as follows: gastrodin 2.0 g, starch 4.5 g, liquid paraffin 100.0 mL, Span80 3.5 g, ECH 5.1 mL, preparation temperature 40℃, and rotational speed 1000 r/min. The particle diameter of gastrodin starch microsphere was (47.69±1.92) μm, the DLE and EE of microsphere were (9.78±0.70)% and (35.72±3.28)%, respectively. It was about (176.92±23.25) s that in adhesive powder resided in nasal cavity, which translated into human nasal residence time was just 20-30 min, while the average residence time of gastrodin starch microspheres was extended to (944.33±68.29) s, translated into human nasal residence time was about 3 h. The cumulated release percent of gastrodin starch microspheres was more than 90% in 3 h. Compared with other in vitro release models, Weibull model was the fittest model to gastrodin starch microspheres, the t50 of gastrodin starch microspheres was 40.08 min, and t90 was 245.73 min. Conclusion: Gastrodin starch microspheres prepared with optimum prescription technology have uniform particle diameter, high DLE and EE. Microspheres have good mucoadhesion and sustained release, ensure that gastrodin release gently and completely during the nasal retention period.
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Objective To investigate effect of hydroxypropyl methyl cellulose (HPMC) to in vitro release characteristics of cefaclor sustained-release tablets.Methods Collected 10 batches of HPMC from different manufacturers.Determined the viscosity, molecular weight and the distribution of molecular weight of HPMC.HPMC from different manufacturers was used as blocking agent for the preparation of cefaclor sustained-release tablets according to the same prescription.Results The molecular weight was positively related to the viscosity of HPMC.The more molecular weight was, the slower the drugs release rate was,the better controlled released.Conclusion HPMC from different manufacturers show different quality stability and effect in vitro release of cefacor sustained-release tablets.
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OBJECTIVE: To investigate the pharmacokinetics of single and multiple oral doses of minocycline hydrochloride extended-release tablets and evaluate its extended-release characteristics by comparing with ordinary tablets. METHODS: Twelve healthy volunteers received a single oral dose of 45, 90 and 135 mg minocycline hydrochloride extended-release tablets respectively with a 10-day washout period. After the single-dose study, the volunteers participated in the multiple dose study in which each volunteer received 90 mg per day for 10 consecutive days. The ordinary tablets were administered by single and multiple doses as reference preparation in the end. The concentrations of minocycline in human plasma were determined by LC-MS method. RESULTS: The main pharmacokinetic parameters of a single dose of minocycline hydrochloride extended-release tablets of 45, 90 and 135 mg in 12 healthy volunteers were as follows: pmax (0.4770±0.1280), (1.011±0.191) and (1.500±0.281) μg · mL-1, tmax(3.3±1.1),(3.6±0.8) and (3.4±0.7) h, t1/2 (17.1±5.4), (18.3±4.9) and (17.9±3.4) h, AUC0-t (9.391±3.019), (20.01±3.07) and (31.81±6.80) μg · h · mL-1, respectively. And those of multiple-dose of minocycline hydrochloride extended-release tablets of 90 mg were as follows: pav(0.8440±0.2250) μg · mL-1, DF(1.1±0.2), pmax(1.438±0.383) μg · mL-1, tmax(3.5±0.8) h, t1/2 (19.3±4.4) h, AUC0-t(31.18±9.39) μg · h · mL-1. The main pharmacokinetic parameters of a single dose of ordinary minocycline hydrochloride tablets of 100 mg were as follows: pmax(1.418±0.427) μg · mL-1, tmax (2.6±0.7) h, t1/2 (16.9±3.9) h, AUC0-t(25.35±5.80) μg · h · mL-1, and those of multiple-dose of ordinary minocycline hydrochloride tablets at 100 mg were as follows: pav(1.229±0.377) μg · mL-1, DF(1.3±0.2), pmax(2.188±0.652) μg · mL-1, tmax(2.3±0.7) h, t1/2 (17.7±2.4) h, AUC0-t(44.83±16.29) μg · h · mL-1, respectively. CONCLUSION: In the range of 45-135 mg, the AUC0-t and pmax of minocycline hydrochloride extended-release tablets increased in a dose-dependent manner after single-dose administration, indicating linear pharmacokinetics. No significant gender differences were found. An accumulation of 50% in AUC0-t occurred after multiple-dose administration. The minocycline hydrochloride extended-release tablets have extended-release character comparing with ordinary tablets.
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OBJECTIVE:To prepare aspirin gastric floating capsule and to study its in vitro drug-release characteristics.METHODS:Aspirin gastric floating capsule was prepared with aspirin as model drug,and with hydroxypropyl methylcellulose(HPMC)under different viscosity and different quantity and carbopol as main excipients.The release rate of the capsules was determined.RESULTS:When the optimal ratio between HPMC K4M and HPMC K15M was3to1,then the in vitro drug release of aspirin gastric floating capsule within0h～10h conformed to apparent zero-order kinetics with rate constant Kr at10.3%/h and release parameter at0.6173.CONCLUSIONS:The prepared capsule has a marked slow-release effect,the quantity and the viscosity of HPMC were the main factors affecting the release rate of gastric floating capsule,the in vitro drug release characteristics were associated with the joint action of bulk erosion and drug diffusion.