ABSTRACT
Abstract Efavirenz is one of the most commonly used drugs in HIV therapy. However the low water solubility tends to result in low bioavailability. Drug nanocrystals, should enhance the dissolution and consequently bioavailability. The aim of the present study was to obtain EFV nanocrystals prepared by an antisolvent technique and to further observe possible effect, on the resulting material, due to altering crystallization parameters. A solution containing EFV and a suitable solvent was added to an aqueous solution of particle stabilizers, under high shear agitation. Experimental conditions such as solvent/antisolvent ratio; drug load; solvent supersaturation; change of stabilizer; addition of milling step and solvents of different polarities were evaluated. Suspensions were characterized by particle size and zeta potential. After freeze- dried and the resulting powder was characterized by PXRD, infrared spectroscopy and SEM. Also dissolution profiles were obtained. Many alterations were not effective for enhancing EFV dissolution; some changes did not even produced nanosuspensions while other generated a different solid phase from the polymorph of raw material. Nevertheless reducing EFV load produced enhancement on dissolution profile. The most important modification was adding a milling step after precipitation. The resulting suspension was more uniform and the powder presented grater enhancement of dissolution efficacy.
Subject(s)
Efficacy/classification , HIV/pathogenicity , Crystallization/instrumentation , Dissolution/methods , Particle Size , Solubility , Pharmaceutical Preparations/administration & dosage , Excipients/pharmacology , Dissolution/classification , Nanoparticles/administration & dosage , MethodsABSTRACT
OBJECTIVE：To prepare and characterize glycyrrhetinic acid （GA）nanoparticles，and to evaluate its in vitro anti-tumor activity. METHODS ：Using PVP K 30 as carrier ，GA nanoparticles were prepared by anti-solvent precipitation and freeze-drying method. X-ray diffraction ，infrared spectrum ，differential scanning calorimetry and granularity analysis were used to characterize the nanoparticles ；HPLC method was used to measure the solubility and drug-loading amount of GA in the nanoparticles. MTT method was used to assay the in vitro inhibition activity of GA raw material and nanoparticles （GA doses were 12.5，25，50，100，200 μmol/L）on human liver cancer cell HepG 2 and calculate its IC 50. RESULTS ：The characteristic peaks of X-ray diffraction and infrared absorption of GA disappeared in the nanoparticles and the endothermic peak changed. The particle size of the nanoparticles was （194.88±23.52）nm，which was lower than （2 592.33±207.51）nm of raw material. The dispersion index was 0.24±0.04，which was higher than 0.15±0.03 of raw material. The average drug-loading amount of GA was 15.99％. Moreover，the solubility of nanoparticles increased from （1.05±0.01）μg/mL to（250.00±0.15）μg/mL. The results of antitumor test in vitro showed that the cell survival rates in the group of GA raw material 200 μmol/L and GA nanoparticles groups were significantly lower than that in blank control group ，and the cell survival rates of GA nanoparticles groups （except for 12.5 μmol/L group）were significantly lower than that of same dose group of raw material （P＜0.01）. IC 50 of GA nanoparticles was 86.3 μmol/L，which was lower than 364.4 μmol/L of raw material. CONCLUSIONS：GA nanoparticles are prepared successfully ；the prepared nanoparticles have small size and uniform distribution ，and the solubility are increased and antitumor activity in vitro are enhanced.
ABSTRACT
OBJECTIVE:To prepare the betulinic acid nanoparticles,and characterize them. METHODS:Using ethanol as sol-vent and water as anti-solvent,anti-solvent recrystallization method was used to prepare betulinic acid nanoparticles. Using particle size as indicator,single factor test and orthogonal test were adopted to optimize the mass concentration of betulinic acid solution, anti-solvent-solvent volume ratio,anti-solvent drip rate,reaction temperature and stirring speed in formulation technology of betulin-ic acid nanoparticles,and verification test was conducted. The betulinic acid nanoparticles were characterized by scanning electron microscopy,laser particle size analyzer,Fourier infrared spectrometer and mass spectrum analyzer. RESULTS:The optimal technol-ogy was as follow as betulinic acid solution mass concentration of 3 mg/mL,anti-solvent-solvent volume ratio of 1:1,anti-solvent drip rate of 8 mL/min,reaction temperature of 20 ℃ and stirring speed of 900 r/min. The average size of prepared betulinic acid nanosuspension was(156.0±8.6)nm(n=3)and the particle size was(235.0±12.2)nm(n=3)after freeze-drying,with nearly spherical appearance,uniform size and regular form. Compared with raw material of betulinic acid,the chemical structure of pre-pared betulinic acid nanoparticles did not change,and there were no significant changes in molecular weight and mass ratio. CON-CLUSIONS:Betulinic acid nanoparticles are successfully prepared.
ABSTRACT
Objective:To prepare celecoxib nanosuspension ( CXB-NSs) and study the pharmacokinetics of CXB-NSs in rats. Methods:CXB-NSs were prepared by an anti-solvent precipitation and high pressure homogenization method. The particle size, polydispersion index ( PdI) and zeta potential of the nanosuspension were studied. Totally 12 Wistar rats were randomly divided into CXB-NSs group and CXB suspension group, and gastric drug dose was 100 mg·kg-1 . CXB concentration in plasma was determined by HPLC and the pharmacokinetic parameters were calculated by 3P97 software. Results: The particle size, polydispersion index, zeta potential of CXB-NSs was (442. 5 ± 61. 9) nm, 0. 312 ± 0. 057 and ( -31. 6 ± 3. 9) mV, respectively. AUC (0-t) of CXB suspension and CXB-NSs was (5.13 ±0.77) and (13.51 ±3.18) mg·L-1·h, half time (t1/2) was (12.31 ±1.91) and (12.73 ±1.83) h, Tmax was (2. 48 ± 0. 37) and (1. 41 ± 0. 27) h and Cmax was (0. 94 ± 0. 31) and (2. 38 ± 0. 25) mg·L-1 , respectively. Conclusion:CXB-NSs can remarkably increase bioavailability in rats.
ABSTRACT
OBJECTIVE: To enhance dissolution rate of silymarin (SM) by forming SM nanoparticles (SM-NA) with supercritical anti-solvent (SAS) method. MOTHODS: Single-factor test was employed to investigate the influencing factors of particle size and yield of SM-NA, such as pressure, temperature, flow rate, and concentration of the solution. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC) were used to determine the state of SM-NA. The dissolution characteristics in vitro were investigated with 0.3% SDS aqueous solution as the solvent and compared with the SM powder. RESULTS: Taking size distribution as well as yield of SM-NA as the evaluation indexes, the optimal prepration parameters were selected as fallowings; pressure 15 MPa, temperature 35℃, flow rate 1.5 mL · min-1, concentration 100 mg · mL. The XRD and DSC of SM-NA described the decrease of SM in crystallinity, and it was transformed mostly with the amorphous state, compared with the SM powder. The accumalte release rate of SM-NA achieved 80% within 10 min, markedly higher than that of the SM powder and its commercial preparation. CONCLUSION: The SM-NA prepared by SAS has remarkablly smaller particle size thus can greatly improve the in vitro release of SM.
ABSTRACT
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.
ABSTRACT
Objective: To prepare the apigenin particles by supercritical CO2 anti-solvent technology, to optimize the preparation process of apigenin particles on the basis of single factor experiments using the average particle size as evaluation index through orthogonal test design, and to investigate the in vitro dissolution rate. Methods: The particle size distribution, scanning electro- microscope (SEM) analysis, infrared spectrum (IR), and differential scanning calorimetry (DSC) were used to validate the selected process. The external dissolution rates of apigenin ingredient and apigenin particles of the optimal process were tested to speculate the bioavailability of apigenin. Results: The optimal process conditions by orthogonal test were set as follows: The proportion of acetone and dimethyl sulfoxide (DMSO) was 24:1, temperature was 40°C, pressure was 10 MPa, solution volumetric flow rate was 2.0 mL/min, and mass concentration of apigenin was 8 mg/mL. Under the optimal conditions, the volume average particle size was obviously smaller than that of ingredient. And the shapes of apigenin were irregular. FTIR and DSC analyses showed that the chemical structure did not change. The results showed that the in vitro dissolution rate of apigenin particles of the optimal process was significantly larger than that of apigenin ingredient. Conclusion: The supercritical CO2 anti-solvent technology is feasible to prepare apigenin particles and promote its bioavailability, and it provides a reference basis for preparing ultrafine particles.