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@#Nanocrystals are nanoscale (1-1000 nm) dispersion systems in which small numbers of surfactants or polymers are used as stabilizers to disperse insoluble drug particles in water or oil. Nanocrystals enjoy not only high drug content, but also a simple and mature preparation process. At present, 24 nanocrystals products that have been marketed mainly focus on enhancing the solubility and bioavailability of poorly soluble drugs. And recent years have witnessed an increasing number of research reports on target drug delivery of nanocrystals through particle size control and surface modification. This paper mainly introduces three targeting strategies for prolonging the in vivo circulation time of nanocrystals, increasing the affinity for tumor cells and achieving the response to internal and external stimuli, and discusses the current challenges in the application of nanocrystal technology to targeted anti-tumor drugs.
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Objective: To prepare a anti-drug-resistant hybrid nanosuspension of quercetin and hydroxycamptothecin by employing the anti-drug resistance property of quercetin. Methods: The ratio of quercetin to hydroxycamptothecin was optimized by in vitro cytotoxicity test. The hybrid nanosuspension of quercetin and hydroxycamptothecin was prepared by the microprecipitation-high pressure homogenization method, with polyethylene glycol-poly(benzyl aspartateic acid)as stabilizers. The particle size, potential, morphology, crystal form and stability of nanosuspensions were studied by the dynamic light scattering, transmission electron micros-copy, differential scanning calorimetry and X-ray powder diffraction. The hemolytic effect of nanosuspension was analyzed by the UV spectrophotometry. The in vitro dissolution of nanosuspensions was investigated by the paddle method. Results: The particle size and Zeta potential of nanosuspensions were(216.3±5.93)nm and(0.197±0.035)mV, respectively. The nanosuspension showed an irregular shape in the transmission electron microscope image. Compared with the two raw drugs, the crystal forms of quercetin and hydroxycamptothecin in nanosuspension was likely transformed in the state of nanosuspension. The nanosuspension showed a good storage and dilution stability, and had good blood compatibility. The dissolution test showed that nanosuspensions could significantly increase the dissolution rate of the two drugs(both P<0.05). Conclusion: The combination of quercetin and hydroxycamptothecin in a favored ratio selected by the present study could significantly improve the antitumor effect of hydroxycamptothecin. The prepared quercetin and hydroxycamptothecin hybrid nanosuspensions showed good pharmaceutical properties, which might be used for further studies on the synergistic and detoxifying effect of the hybrid nanosuspensions.
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Objective In order to solve the problem of poor water solubility of quercetin, quercetin nanosuspensions (Q-NSps) with high drug loading and suitable for intravenous administration was prepared, and study its anti-tumor effect in vitro and in vivo. Methods Quercetin was made into nanoparticles (Q-NSps) via the method of anti-solvent precipitation combined with high-pressure homogenization using polyethylene glycol 1 000 vitamin E succinate (TPGS) as stabilizer. The particle size of the resultant nanoparticles was measured by dynamic light scattering and the morphology was observed by scanning electron microscopy. The drug loading and the in vitro drug release were measured using HPLC analysis. In the meantime, the lyoprotectants were screened, the storage stability, hemolysis, and the suitability for intravenous injection were also studied; The in vitro anti-tumor activity of quercetin and its nanoparticles were assessed in contrast using MTT assay and the in vivo anti-tumor therapeutic efficacy was investigated using 4T1 tumor bearing mice. Results Q-NSps had uniform size and spherical shape, the average particle size was 143.9 nm, the polydispersity index (PDI) was 0.231, and the Zeta potential was -22.6 mV. The drug loading content was (45.82 ± 1.73) %. Using 1% maltose as lyoprotectant, Q-NSps could be lyophilized and then reconstituted into nanoparticles of the similar size. Q-NSps were stable for 30 d at storage, showed no hemolysis, and were suitable to intravenous administration. The resultant nanosuspensions displayed a good sustained in vitro release, and the cumulative release reaching 82.86% at 144 h. Q-NSps showed significantly higher growth inhibition against 4T1, HeLa, and HepG2 cell lines. The in vivo study demonstrated that Q-NSps (45 mg/kg, iv) had the similar antitumor therapeutic efficacy as paclitaxel injections (56.78% vs 55.08%, P > 0.05). Conclusion The obtained Q-NSps had small particle size, good stability, and significantly improved anti-tumor effect of quercetin in vitro and in vivo, so Q-NSps are promising to be a antitumor drug for application in clinic.
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Objective: To prepare sustained-release tablets of tilianin nanosuspension lyophilized powder. The factors that might influence drug release and release mechanism were studied in present study. Methods: High pressure homogenization method was used to prepare tilianin nanosuspension. Lactose and mannitol (3:1) were employed as freeze-drying protective agent to prepare lyophilized powder. HPMC was used as framework material to prepare sustained-release tablets of tilianin nanosuspension lyophilized powder. Based on single factor test, the effects of proportion and amounts of HPMC K4M and HPMC K15, amounts of PEG 4000 and magnesium stearate on in vitro drug release of sustained-release tablets were investigated. Orthogonal test was designed to gain the optimum prescription. Results: The particle size and zeta potential of tilianin nanosuspension were (164.41 ± 9.72) nm and (-37.21 ± 2.38) mV, respectively. The particle size and zeta potential of re-dispersed freeze-drying products were (211.83 ± 11.26) nm and (-31.66 ± 2.92) mV, respectively. The optimum prescription was as follow: the proportion and amounts of HPMC K4M and HPMC K15 were 2:1 and 40 mg, amounts of PEG 4000 was 20 mg, and amounts of magnesium stearate were 0.5%. Sustained release tablets of tilianin nanosuspension were well accorded with Higuchi kinetics model. The equation was Mt/M∞ = 0.286 8 t1/2-0.073 8, r2 = 0.981 4. And the cumulative release could achieve 92.36% in 12 h. The drug release from the tablets was controlled by diffusion and degradation of the matrix. Conclusion: The preparation technology of sustained release tablets of tilianin nanosuspension lyophilized powder has good reproducibility. This sustained release tablets could control the release of tilianin
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Objective: To prepare osthole solid dispersions (Ost-SD), osthole phospholipids complex (Ost-PC), and osthole nanosuspensions (Ost-NS), and compare their effects on the pharmacokinetics in SD rats in vivo. Methods: Solvent evaporation method was used to prepare Ost-SD and Ost-PC. Their existential state of Ost in Ost-SD and Ost-PC were analyzed by X-ray power diffraction (XRPD). High pressure homogenization method was employed to prepare Ost-NS, its particle size and Zeta potential were studied. The dissolution in vitro of Ost-SD, Ost-PC, and Ost-NS were also studied compared to Ost suspension. SD rats in each group were ig administered with Ost, Ost-SD, Ost-PC, and Ost-NS, respectively. The concentration of Ost in blood was analyzed by HPLC, and the main pharmacokinetic parameters were obtained. The pharmacokinetic behavior and bioavailability were also been compared. Results: The results of XRPD indicated that Ost showed an amorphous state in Ost-SD and Ost-PC. The average particle size and Zeta potential of Ost-NS were (161.37 ± 3.77) nm and (-29.16 ± 1.83) mV, respectively. The results of dissolution in vitro indicated that the dissolution of Ost was improved greatly by Ost-SD, Ost-PC, and Ost-NS. The results of pharmacokinetics in vivo showed that Cmax, AUC0~t and AUC0~∞ of Ost-SD, Ost-PC, and Ost-NS were enhanced greatly compared to Ost. The bioavailability of Ost-SD, Ost-PC,and Ost-NS were enhanced to 165.92%, 138.46%, and 259.35%, respectively. Conclusion: Ost-SD, Ost-PC, and Ost-NS can enhance the bioavailability of Ost in SD rats notably. In addition, Ost-NS can give a better effect.
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Objective:To prepare daidzein nanosuspension capsules,and to investigate intestinal absorption and oral bioavailability by comparing with commercial daidzein capsules. Method:Daidzein nanosuspensions were prepared by precipitation method combined with high pressure homogenization,orthogonal design method was utilized to optimize its formulation.Daidzein nanosuspensions was characterized by X-ray powder diffraction(XRPD),Fourier transform infrared spectroscopy(FT-IR),transmission electron microscope(TEM),and indexes including mean particle size,polydispersity index(PDI),and Zeta potential.Intestinal absorption study was carried out to compare the accumulative permeated amount of daidzein from daidzein nanosuspensions and commercial daidzein capsules.Biodistribution of daidzein in gastrointestinal tract was investigated,and oral bioavailability was examined through pharmacokinetic study by HPLC. Result:The in vitro small intestinal absorption enhancement ratio of daidzein nanosuspension capsules was approximately 2.49-fold higher than that of commercial capsules(PConclusion:Daidzein nanosuspensions prepared by combined method can be applied to the production of capsules,which is beneficial to increase the absorption of drug in small intestine and improve its bioavailability after oral administration.
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OBJECTIVE： To investigate the effects of crystal form on in vivo and in vitro behavior of Astilbin nanosuspensions （AT-NS）. METHODS： AT-NS1 and AT-NS2 were prepared by precipitation method and miniaturized media milling method respectively. The particle size and polydispersity index （PDI） were determined by laser particle size analyzer. X-ray diffraction （XRD）， scanning electron microscopy （SEM）， HPLC and paddle method were used to analyze and compare the structure characteristics， appearance morphology and in vitro dissolution of AT raw material， AT-NS1 and AT-NS2. Totally 15 healthy male SD rats were randomly divided into AT raw material， AT-NS1 and AT-NS2 group， with 5 rats in each group. They were given relevant medicine suspension 120 mg/kg （using water as solvent） intragastrically； blood samples were collected from orbit before medication （0 min） and 5， 10， 20， 30， 60， 120， 240， 480 min after medication. Using rutin as internal standard， HPLC method was used to determine plasma concentration of AT in rats. Pharmacokinetic parameters were calculated by using DAS 2.0 software and then compared. RESULTS： The particle sizes of AT-NS1 and AT-NS2 were （212.48±0.32） nm and （226.36±2.29） nm， respectively； PDI were 0.129 3±0.026 3 and 0.254 7±0.012 4. XRD analysis showed AT-NS1 was amorphous， and AT-NS2 was crystalline. Diffraction peaks of both were different from those of AT raw material. SEM analysis showed that AT-NS1 and AT-NS2 were similar in morphology， and they were spherical and uniform in size； AT raw material was lump with large particle size and different sizes. Results of dissolution tests showed that accumulative dissolution of AT raw material， AT-NS1 and AT-NS2 were 4.54％， 35.01％， 12.22％ at 1 h； accumulative dissolution of them were 24.01％， 81.14％， 64.69％ at 12 h； accumulative dissolution of them were 36.04％， 84.47％， 85.86％ at 24 h， respectively. Results of pharmacokinetic study showed， compared with AT raw material group， cmax and AUC0-∞ of AT-NS1 and AT-NS2 groups as well as t1/2z of AT-NS1 group were increased significantly， while tmax of AT-NS1 group was significantly reduced significantly （P＜0.05）. Compared with AT-NS2 goup， cmax， AUC0-∞ and t1/2z of AT-NS1 group were increased significantly， while tmax was reduced significantly （P＜0.05）. CONCLUSIONS： When AT is prepared into NS， dissolution in vitro and oral absorption in vivo of AT are increased significantly. In a short time， the dissolution/absorption of amorphous NS is faster than crystalline NS.
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The single-factor test was used to optimize the high-pressure homogenization method to prepare the phenolic extract nanosuspensions(DBNs). The physicochemical properties of the obtained nanosuspensions were characterized and the cumulative release in vitro was evaluated. The results showed that the drug concentration was 0.5 g·L~(-1), the mass concentrations of PVPK30 and SDS were 0.5 and 0.25 g·L~(-1), respectively, the probe ultrasonic time was 5 min, the homogenization pressure was 900 bar, and the number of homogenization was 2 times. The prepared DBNs had an average particle size of(168.80±0.36) nm, polydispersity index(PDI) of 0.09±0.04, stability index(SI) of 0.85, and DBNs were stable for storage within 30 days. Scanning electron microscopy showed that the particle size of the dragon's blood extract was reduced and the uniformity was improved in the obtained nanosuspensions. X-ray diffraction pattern and differential scanning calorimetry showed that the phenolic extract of dragon's blood was still in an amorphous state after being prepared into nanosuspensions. The results of saturated solubility measurement showed that the solubility of DBNs lyophilized powder reached 6.25 g·L~(-1), while the solubility of DB raw powder was only 28.67 mg·L~(-1). The in vitro dissolution experiments showed that DBNs lyophilized powder accumulated in gastrointestinal fluid for 8 h. The release amount was 90%,the cumulative release of the raw powder in the gastrointestinal fluid for 24 h was less than 1%, and the solubility and dissolution rate of the DBNs lyophilized powder were significantly higher than the DB raw powder. The method is simple in process and convenient in operation, and can successfully prepare uniform and stable nanosuspensions to improve its solubility, and provides a research basis for solving the application limitation of dragon's blood extract.
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Calorimetry, Differential Scanning , Nanoparticles , Particle Size , Plant Extracts , Chemistry , Solubility , Suspensions , X-Ray DiffractionABSTRACT
The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills (GNDP) by transforming lignans of Herpetospermum caudigerum (HL) composed of herpetrione (HPE) and herpetin (HPN) into nanosuspension (HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles (HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy (PCS), zeta potential measurement, and scanning electron microscopy (SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro, NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC, C and decrease in T when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability.
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Animals , Humans , Male , Rats , Benzofurans , Chemistry , Biological Availability , Cucurbitaceae , Chemistry , Drug Carriers , Chemistry , Drug Compounding , Drug Stability , Freeze Drying , Furans , Chemistry , Lignans , Chemistry , Pharmacokinetics , Nanoparticles , Chemistry , Particle Size , Plant Extracts , Chemistry , Rats, Sprague-Dawley , SolubilityABSTRACT
The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills (GNDP) by transforming lignans of Herpetospermum caudigerum (HL) composed of herpetrione (HPE) and herpetin (HPN) into nanosuspension (HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles (HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy (PCS), zeta potential measurement, and scanning electron microscopy (SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro, NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC, C and decrease in T when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability.
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Animals , Humans , Male , Rats , Benzofurans , Chemistry , Biological Availability , Cucurbitaceae , Chemistry , Drug Carriers , Chemistry , Drug Compounding , Drug Stability , Freeze Drying , Furans , Chemistry , Lignans , Chemistry , Pharmacokinetics , Nanoparticles , Chemistry , Particle Size , Plant Extracts , Chemistry , Rats, Sprague-Dawley , SolubilityABSTRACT
@#:In order to improve the compliance of patients with Alzheimer′s disease and maintain the continuity of treatment by reducing administration frequency of memantine hydrochloride, a series of memantine long-acting nanosuspension-based injectable formulations were prepared using a hydrophobic salt formation method. Four hydrophobic salt forms of memantine were prepared, including memantine oleate(Mem-Ole), memantine stearate(Mem-Ste), memantine palmitate(Mem-Pal)and memantine pamoate(Mem-Pam). The salt forms of memantine were characterized using fourier transform infrared(FTIR)spectroscopy, proton nuclear magnetic resonance(1H NMR)spectroscopy and powder X-ray diffraction(PXRD)analysis. The equilibrium solubilities of different salt forms of memantine and the in vitro drug release of long-acting injectable formulations were investigated. In comparison with memantine alone, the equilibrium solubilities of Mem-Ole, Mem-Ste, Mem-Pal and Mem-Pam in simulated body fluid were decreased by 95. 1%、96. 2%、96. 7% and 99. 6%, respectively. Meanwhile, the equilibrium solubilities of Mem-Pam in simulated body fluid with pH ranging from 5 to 8 were all lower than 0. 07 mg/mL. The order of the in vitro drug release rate of the four long-acting injectable formulations with nanosuspensions of memantine was Mem-Ste> Mem-Pal≈Mem-Ole> Mem-Pam> Memantine. The Mem-Pam nanosuspensions could sustain drug release for seven days and exhibited a zero-order drug release profile(y=0. 549 9x+7. 594 2, r=0. 988 3). In conclusion, injectable Mem-Pam nanosuspensions showed desired drug release behavior and might potentially be applied in vivo for a week with a steady plasma drug concentration-time profile.
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AIM To prepare nanosuspensions of flavonoids from Glycyrrhizae Radix et Rhizoma and to determine the in vitro dissolution rate.METHODS Precipitation-high pressure homogenization method was adopted in the preparation of nanosuspensions.With mean particle size and polydispersity index (PDI) as evaluation indices,concentrations of flavonoids,povidone K30 (PVP K30) and polyethylene glycol 400 (PEG 400) as influencing factors,central composite design-response surface method was applied to optimizing the preparation.For the freedried powder prepared by freeze-drying method,the optimal kind and ratio of lyoprotectant were screened.Then the in vitro dissolution rates of freeze-dried powder and physical mixture were compared.RESULTS The optimal conditions were determined to be 10.00 mg/mL for flavonoids' concentration,and 2.30 mg/mL for both PVP K30 and PEG 400 concentrations,the mean particle size and PDI were (172.3 ± 1.2) nm and 0.175 ± 0.004,respectively.The optimal lyoprotectant was 5％ mannitol-lactose (3 ∶ 2),the mean particle size and PDI after redissolution were (239.7 ±2.1) nm and 0.193 ±0.032,respectively.The in vitro dissolution rate of lyoprotectant reached 87.7％ within 60 min,which was much higher than that of physical mixture (less than 30％).CONCLUSION Nanosuspension can effectively improve the in vitro dissolution rate of flavonoids from Glycyrrhizae Radix et Rhizoma.
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Objective To study the feasibility of preparing insoluble flavonoids nanosuspensions (NS) by miniaturized media milling. Methods The miniaturized media milling method was constructed with the magnetic stirrer, vial and zirconia beads as the power plant, milling chamber and milling media to prepare the nanosuspensions of four flavonoids: quercetin (QCT), baicalin (BCN), puerarin (PRN), and silymarin (SLR). The process of stirring speed, the amount of milling medium and the milling time were optimized with average particle size, polydispersity index (PDI) and stability index (SI) as indicators. Results The optimized process of stirring speed, the amount of milling medium and the milling time of QCT-NS, BCN-NS, PRN-NS and SLR-NS were QCT-NS 800 r/min, 8 h, 1:1, BCN-NS 800 r/min, 24 h, 1:1, PRN-NS 800 r/min, 24 h, 2:1, SLR-NS 800 r/min, 12 h, 1:1. The average particle sizes of QCT-NS, BCN-NS, PRN-NS and SLR-NS prepared with the optimized process were below 400 nm. The PDI of QCT-NS, BCN-NS and SLR-NS was below 0.3 (PRN-NS) and SI was above 0.75, the PDI and SI of PRN-NS were 0.41 and 0, respectively. Conclusion The miniaturized media milling methods for preparation of insoluble flavonoids NS is simple, stable and feasible, and it is worth for further study.
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AIM To prepare diosgenin nanosuspensions.METHODS The nanosuspensions prepared by media milling method were solidificated by freeze drying method.With particle size and polydispersity index (PDI) as evaluation indices,stabilizer kind,ratio of diosgenin to stabilizer,ratio of preliminary nanosuspension volume to grinding bead amount,milling time,lyoprotectant kind and its amount as influencing factors,single factor test was applied to screening preparation and solidification processes.The morphology of nanosuspensions was observed,then the particle sizes and polydispersity indices of nanosuspensions and freeze-dried powder were determined.RESULTS The optimal conditions were determined to be 6:1 for ratio of diosgenin to Pluronic F127 (stabilizer Ⅰ),50:1 for ratio of diogenin to sodium dodecyl sulfate (SDS,stabilizer Ⅱ),1:4 for ratio of preliminary nanosuspension volume to grinding bead amount,120 min for milling time,and 8％ PEG-6000 and 2％ mannitol as lyoprotectants.The average particle size and polydispersity index of rod-like or flaky nanosuspensions were (348.1 ±14.2) nm and 0.244 ± 0.059,respectively,which were lower than those of freeze-dried powder.At room temperature,the particle sizes of nanosuspensions and freeze-dried powder remained stable within 35 d and 3 months,respectively.CONCLUSION The physical stability of diosgenin freeze-dried powder is superior to that of its nanosuspensions,which can be used after being reconstituted.
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AIM To prepare diosgenin nanosuspensions.METHODS The nanosuspensions prepared by media milling method were solidificated by freeze drying method.With particle size and polydispersity index (PDI) as evaluation indices,stabilizer kind,ratio of diosgenin to stabilizer,ratio of preliminary nanosuspension volume to grinding bead amount,milling time,lyoprotectant kind and its amount as influencing factors,single factor test was applied to screening preparation and solidification processes.The morphology of nanosuspensions was observed,then the particle sizes and polydispersity indices of nanosuspensions and freeze-dried powder were determined.RESULTS The optimal conditions were determined to be 6:1 for ratio of diosgenin to Pluronic F127 (stabilizer Ⅰ),50:1 for ratio of diogenin to sodium dodecyl sulfate (SDS,stabilizer Ⅱ),1:4 for ratio of preliminary nanosuspension volume to grinding bead amount,120 min for milling time,and 8％ PEG-6000 and 2％ mannitol as lyoprotectants.The average particle size and polydispersity index of rod-like or flaky nanosuspensions were (348.1 ±14.2) nm and 0.244 ± 0.059,respectively,which were lower than those of freeze-dried powder.At room temperature,the particle sizes of nanosuspensions and freeze-dried powder remained stable within 35 d and 3 months,respectively.CONCLUSION The physical stability of diosgenin freeze-dried powder is superior to that of its nanosuspensions,which can be used after being reconstituted.
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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.
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Animals , Humans , Male , Rats , Biological Availability , Cell Line , Chemistry, Pharmaceutical , Methods , Drug Carriers , Chemistry , Drug Delivery Systems , Lignans , Chemistry , Pharmacokinetics , Nanoparticles , Chemistry , Particle Size , Rats, Wistar , Solubility , X-Ray DiffractionABSTRACT
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.
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Objective:To prepare nevirapine nanosuspensions ( Nev-NS) and study the pharmacokinetics in rats. Methods:Nev-NS was prepared by a high pressure homogenization technology. The particle size, PDI and Zeta potential of the nanosuspensions were used as the indices to determine the influencing factors in the preparation process. Nevirapine plasma concentration was detected by HPLC and the pharmacokinetic parameters were calculated by 3P97 software. Results: The particle size, PDI and Zeta potential of Nev-NS was (456. 1 ± 72. 1) nm, 0. 441 ± 0. 072 and ( -24. 4 ± 4. 7) mV, respectively. AUC0-12 of Nev and Nev-NS was (7. 57 ± 0.52) and (11.72 ±1.83) mg·h·L-1, t1/2 was (2.45 ±0.31) and (3.16 ±0.39) h, Tmax was (1.43 ±0.38) and (1.61 ± 0. 32) h and Cmax was (1. 62 ± 0. 42) and (3. 15 ± 0. 52) mg·L-1 , respectively. Conclusion:Nev-NS can improve the pharmacoki-netic behavior of Nev in rats significantly, and obviously enhance the bioavailability when compared with nevirapine suspensions.