Preparation and in vitro release of tacrolimus-loaded cationic nanoemulsion-based in-situ gel / 药学实践杂志

Objective In order to improve the problems of poor water-solubility and low bioavailability of ocular tacrolimus, a cationic nanoemulsion in-situ gel of tacrolimus was developed and its drug release behavior in vitro was studied to provide a basis for further research. Methods Tacrolimus-loaded cationic nanoemulsion was prepared by high pressure homogenization and dispersed in poloxamer 407 and poloxamer 188 to prepare tacrolimus-loaded cationic nanoemulsion-based in-situ gel. The membraneless dissolution model was used to study the in vitro drug release behavior. Results The inverse glass bottle method was used to determine the gelation temperature. The optimal formulation of gel matrix was screened out as 26% poloxamer 407 and 12% poloxamer 188. The in vitro release results showed that the rate of gel dissolution determined the in vitro drug release. Conclusion Tacrolimus-loaded cationic nanoemulsion-based in-situ gel is successfully prepared. Its in vitro drug release is stable. It meets the requirement of ophthalmic formulation and shows good prospects for ocular application.

Study on Preparation of Paclitaxel-sorafenib-PLGA-loaded Embolic Microspheres and in vitro Drug Release Characteristics / 中国药房

OBJECTIVE： To prepare Paclitaxel-sorafenib-PLGA-loaded embolic microspheres， and to establish a method for the content determination and investigate their in vitro drug release characteristics. METHODS： Paclitaxel-sorafenib-PLGA-loaded embolic microspheres were prepared by emulsification-solvent evaporation method. HPLC method was used to determine the contents of paclitaxel and sorafenib in Paclitaxel-sorafenib-PLGA-loaded embolic microspheres； drug-loading amount and encapsulation efficiency were calculated. The determination was performed on Agilent TC-C18 column with mobile phase consisted of water-acetonitrile （40 ∶ 60，V/V） at the flow rate of 1.0 mL/min. The detection wavelength was set at 228 nm， and column temperature was 28 ℃. The sample size was 10 μL. The morphology of the microspheres was observed by optical microscopy and scanning electron microscopy. The particle size and granularity distribution of microspheres were measured by laser granularity analyzer. The release rates of paclitaxel and sorafenib were determined by HPLC under physiological temperature （37 ℃）. The reaction rate constants were predicted by Arrhenius equation at 37 ℃， and compared with the measured value （37 ℃）. RESULTS： The linear range of paclitaxel and sorafenib were 2.0-400.0 μg/mL （both r＝0.999 6）. The quantitative limits were 1.902 6 and 1.890 2 μg/mL， and detection limits were 0.985 5 and 1.264 5 μg/mL， respectively. RSDs of precision， stability and reproducibility tests were all lower than 2％. The recoveries were 99.00％-102.91％ （RSD＝1.12％， n＝9） and 98.39％-102.96％ （RSD＝1.94％， n＝9）. The surface of the microspheres were spherical， smooth and no protuberance and no adhesions. The average particle size was （139±1.16） μm. Drug-loading amounts of paclitaxel and sorafenib were 1.12％ and 0.85％， respectively. The encapsulation efficiency were 73.11％ and 58.65％， respectively. Accumulative release rates were （71.83±3.96）％ and （81.44±6.02）％ within 41 d at 37 ℃. RSDs for relative standard deviation of prediction reaction rate constant to measured value were less than 10％ for paclitaxel and sorafenib. The similarity factors were 83.53 and 73.95. CONCLUSIONS： Paclitaxel-sorafenib-PLGA-loaded embolic microspheres are successfully prepared. The microspheres have good morphology and sustained release. The predicted release curve is well correlated with the measured release curve. Established determination method is simple and stable.

In vitro release and gastrointestinal absorption of novel pyridostigmine bromide nanoemulsion / 中国药理学通报

Aim To prepare the novel pyridostigmine bromide nanoemusion(PPNE)and study its release in vitro, and to investigate the intestinal absorption. Methods Pyridostigmine bromide (PB)and PPNE were tested by HPLC in pH 1 .2 HCl,pH 6.8,pH 7.4,pH 7.8 PBS.Rat single pass intestinal perfusion method was employed to investigate the absorption mechanism of PB and PPNE.Results PB release rate was faster than PB in the four release media;the intes-tinal absorption rate constant(Ka )and apparent perme-ability coefficient(Papp)of PPNE were increased in the duodenum,jejunum,ileum and colon segments.PB and PPNE had significant difference in the duodenum, jejunum,ileum and colon segments by t test (P <0.05).Conclusions PPNE can improve the bioavail-ability of drugs,increase the drugs permeability,sig-nificantly improve the absorption of the drugs in the in-testinal segments. PPNE has obviously sustained effects.

Preparation of Dexibuprofen Sustained-release Pellets and Analysis on Drug Release Behavior / 中国药房

OBJECTIVE:To prepare dexibuprofen sustained-release pellets,and to analyze the drug release behavior in vitro. METHODS:Centrifugal granulation powder layering-eudragit dispersion coating method was used to prepare dexibuprofen sus-tained-release pellets using 3%HPMC as adhesive agent. The formula of the pellets was optimized by orthogonal test with weight ra-tio of sucrose to dexibuprofen,weight ratio of HPMC to Eudragit NE30D and coating weight as factors,using 1,4 and 10 h accu-mulated release rate (Q) as index. The release of the drug from the pellets was analyzed. RESULTS:The optimized formulation was that the proportion of sucrose to drug was 1:10,the weight ratio of HPMC to Eudragit NE30D was 1.5:1,the increased weight of coating material was 8%. Q1 h,Q4 h and Q10 h of prepared pellets were 21%,57% and 89%,respectively(n=3). The co-rrelation coefficient of zero-order,one-order and Higuchi equation release model were 0.956 6,0.989 9,0.996 5. CONCLUSIONS:Prepared pellets show good sustained-release effect in vitro. Drug release of pellets is more in accordance with Higuchi equation.

Preparation and Drug Release in vitro of N-Trimethyl Chitosan-coated Sparfloxacin Nanoliposomes in Situ Gels / 中国药师

Objective:To prepare N-trimethyl chitosan (TMC)-coated sparfloxacin (SL) nanoliposomes in situ gels(ISG)and in-vestigate the drug release in vitro.Methods:SL liposomes were prepared by a pH gradient method , and then homogenized to nanolipo-somes by high pressure .TMC was used as the coating material to prepare TMC-coated SL nanoliposomes .Poloxamer 407 was used as the gel base, and the optimal amount was selected according to the gelation temperature .TMC-coated SL nanoliposomes ISG was pre-pared using a cold method , and the morphology , size, zeta potential and entrapment efficiency of TMC-coated SL nanoliposomes were studied.A membraneless model was used to study the drug release in vitro, and the result was compared with that of TMC-coated SL nanoliposomes.Results:The optimal amount of poloxamer 407 in the formula was 25%, and the gelation temperature was 23.6℃in the artificial tears and 33 .5℃in the diluted artificial tears .The morphology of TMC-coated SL nanaoliposomes in the ISG was spherical with the mean diameter of (96.8 ±1.5) nm, zeta potential of (46.2 ±1.4) mV and entrapment efficiency of (76.6 ±2.4) %, and the indices had no significant difference when compared with those of TMC-coated SL nanoliposomes .Both the drug release in vitro and gel dissolution profile of TMC-coated SL nanoliposomes ISG exhibited the characteristics of zero-order kinetics, and compared with that of TMC-coated SL nanoliposomes , the sustained release property of the ISG was more significant .Conclusion:TMC-coated SL nanoli-posomes ISG has promising gelation temperature and notable sustained release property .

Preparation and formulation optimization of Rheum Colon Targeted Pellets / 中草药

Objective: To prepare the pH dependent-microbially triggered colon targeted pellets of Rheum and optimize the preparation formulation of the targeted pellets. Methods: The pill-core was prepared by dropping preparation method, the pill-core fomulation was optimized by the orthogonal test, with drug loading, entrapment rate, and releasing rate as indexes. With release performance as index, the lagging cover weight increment was screened, the Rheum pellet that released at colon was obtained. Results: The 2% alginate-pectin solution, 0.7% chitosan solution, 1% CaCl2 solution, chitosan-CaCl2 solution with pH of 6.0, and the 4∶1 quantity of reagent (Rheum-accessory) were chosen as the top gallant fomulation to prepare the pill core, then enteric coating weight increased to 30% and the enteric coated-pellet was obtained. In gastric juice after 2 h and in small intestinal juice after 3 h, the coated pellet is cumulatively released to 2.01% and 8.72%, respectively, and released to 92.58% in the colon fluid after 4 h. Conclusion: The preparation fomulation of colon targeted pellet of Rheum is definited, and the colon targeted release is preliminary implemented.

Study on the Formulation Optimization of Entecavir PLGA Sustained-release Microspheres and Its Drug Release in vitro / 中国药房

OBJECTIVE:To optimize the formulation of entecavir PLGA sustained-release microspheres,and explore its drug release in vitro. METHODS:PLGA sustained-release microspheres was prepared by emulsification-solvent evaporation method. Us-ing composite score of entrapment efficacy and drug loading as indexes,orthogonal test was designed to optimize drug amount, drug-PLGA mass ratio,PLGA mass concentration,oil phase-aqueous phase volume ratio and polyvinyl alcohol (PVA) concentra-tion;and validation test was also conducted. The prepared microsphere morphology,particle size and durg release in vitro were de-tected. RESULTS:The optimized formulation was entecavir 20 mg,entecavir-PLGA mass ratio 1∶10,PLGA mass concentration 200 mg/ml,oil phase-aqueous phase volume ratio 1∶10,and PVA concentration 2%;entrapment efficacy was (86.52 ± 3.25)%, drug loading was(18.36±1.37)%,RSDs were lower than 5.0%(n=3);it was round and smooth in appearance with average par-ticle size of 58.35 μm;Q10 h,Q96 h and Q360 h were 9.6%,42.9% and 89.6%,and the drug release in vitro fitted to Higuchi model (r2=0.965 8). CONCLUSIONS:Entecavir PLGA sustained-release microspheres prepared by optimized formulation has good sus-tained-release performance.

Study on Formulation Optimization of Nicorandil Sustained-release Matrix Tablet and Drug Release in vitro / 中国药房

OBJECTIVE:To optimize the formulation optimization of Nicorandil sustained-release matrix tablet,and evaluate its drug release properties in vitro. METHODS:Based on single factor test,powder direct compression method was used,using nicorandil cumulative release rate (Q) in 1,4,8,12 h as evaluation indexes,central composite design-response surface method was adopted to optimize the amount of hydroxypropyl methylcellulose(HPMC)and ethyl cellulose(EC);Q values within 12 h in different pH (1.0,5.0,6.8,7.4) media were compared. RESULTS:The optimized formulation (every tablet) was nicorandil 10 mg,HPMC 150 mg,EC 90 mg,microcrystalline cellulose 80 mg,lactose 60 mg,magnesium stearate 2%. Q1 h,Q4 h,Q8 h and Q12 h of the obtained formulation were 23.6%,51.3%,83.7% and 96.9%,respectively;deviation from the predicted values were 2.1%,1.6%,1.0%,0.2%. Q values were similar in pH 1.0-7.4 at different time points. CONCLUSIONS:The obtained Nicor-andil sustained-release matrix tablet by optimal formulation shows sustained-release effect,and the change of pH 1.0-7.4 has no in-terference in the release characteristics of main drug.

Formulation Optimization of Asiaticoside Cationic Liposomes by Using Central Composite Design-response Surface Method / 中国药房

OBJECTIVE:To optimize the formulation of Asiaticoside cationic liposomes,and to investigate the characteristics of drug release in vitro. METHODS:The thin film dispersion method was used to prepare liposome;using encapsulation efficiency and drug-loading amount as index,the formulation of Asiaticoside liposomes was optimized by central composite design-response surface method with the ratio of drug to lipid(X1),the ratio of cholesterol to lipid(X2)and the concentration of D-mannose(X3) as factors. Using sodium lauryl sulfate as medium,in vitro release characteristics of cationic liposomes prepared with 1%octadecyl-amine was investigated by bag filter method,and compared with those of Asiaticoside solution and common liposome. RESULTS:The optimal formulation was X1 0.07,X2 0.17 and X3 0.03 g/ml. The encapsulation efficiency was (75.529 ± 1.071)%,and drug-loading amount was(2.539±0.029)%(n=3);the deviation from the predicted values were -0.217% and 0.205%;1% oc-tadecylamine was add into formulation to obtain cationic liposomes,and the Zeta potential had changed from -5.6 mV to 20.8 mV. in vitro accumulative release rates of Asiaticoside solution,common liposomes and cationic liposomes were 89.13%(12 h), 87.58%(72 h) and 94.46%(72 h),and the latter was in line with Weibull model. CONCLUSIONS:Asiaticoside cationic lipo-somes have high encapsulation efficiency,and can releases for 72 h.

Preparation and quality evaluation of starch microspheres of diclofenac sodium / 中国药学杂志

OBJECTIVE: To prepare starch microspheres of diclofenac sodium by inverse crosslink emulsification method. METHODS: Mean particle size and encapsulation efficiency of starch microspheres were used as indicators, single factor and orthogonal design methods were performed for optimizing preparation process and formulations of starch microspheres. The appearance and structure of the microspheres were researched by optical microscope, transmission electron microscope, infrared spectroscopy and differential thermal analyzer. In vitro drug release behavior was investigated by dialysis method. RESULTS The preparation conditions optimized by orthogonal design; the concentration of starch 10%, crosslinking temperature 55℃, dosage of cross-linking agent 0.2 g, the volume ratio of oil phase and water 5:1, amount of emulsifier 5 mL, cross-linking time 60 min. Starch microsphere obtained by above condition has an average particle size of 9 μm, appearance is irregular spherical shape, and encapsulation efficiency was 67.52%. Results of IR spectra and DTA curves showed that starch cross-links have happened. CONCLUSION In vitro releasing curve showed that the diclofenac sodium starch microspheres have good sustain release effect, drug release complies with the Weibull equation.

Preparation of Poly( lactide-co-glycolide)Microspheres Containing Total Alkaloids of Panzeria alaschanica / 中国药房

OBJECTIVE:To optimize the formulation and technology of poly(lactide-co-glycolide)(PLGA)microspheres con-taining total alkaloids of Panzeria alaschanica,and to prepare microspheres and conduct quality investigation. METHODS:PLGA microspheres containing total alkaloids of P. alaschanica (PTPM) was prepared by double emulsion-solvent evaporation method. The formulation of microspheres was optimized by L9(34) orthogonal design using mass concentration of PLGA,PVA concentra-tion,ratio of water phase to oil phase as factor,drug-loading amount,encapsulation efficiency,yield as index. The morphology, particle size and drug release of microspheres were all investigated. RESULTS:The optimal formulation was as follows as the mass concentration of PLGA 200 mg/ml,the concentration of PVA 2%,and the water phase-oil phase ratio 1:5. In validation test,aver-age encapsulation efficiency was(83.2±2.4)%,average drug-loading amount(4.16±0.17)%,average yield(86.7±3.6)%,and comprehensive score (95.7 ± 4.4)%;all RSDs were lower than 5.0%(n=3). Prepared microspheres were spherical with smooth surface and uniform particle size. The average particle size was(22.3±2.4)μm and accumulative release rate of 24 h was(82.3± 3.5)%,which conformed to first-order release model(r=0.972 4). CONCLUSIONS:Optimized technology is stable. Prepared mi-crospheres show good sustained-release property,and fit to quality requirements.

Preparation and Drug Release in vitro of Indometacin Enteric Dropping Pills / 中国药师

Objective:To prepare indometacin ( IDM) enteric dropping pills and study the drug release in vitro. Methods:Using PEG6000 as the base, the optimal formula and preparation process of IDM dropping pills were screened by an orthogonal design. IDM dropping pills were coated by polyacrylic resin II as the enteric coating material. Compared with the marketed IDM enteric tablets, the drug release of IDM enteric dropping pills in vitro was studied using a suspended basket method. Results:The optimal preparation con-ditions of IDM dropping pills were as follows:the ratio of IDM and base was 1∶3, the dropping speed was 65 drops/min, the dropping temperature was 90℃ and the temperature of the cooling solvent was 5℃. IDM dropping pills and the marketed tablets were both with little drug release in acidic solvent. In pH 6. 8 phosphate buffer solution, IDM enteric dropping pills showed much quicker drug release than the marketed enteric tablets (P<0. 05). Conclusion:IDM enteric dropping pills exhibit enteric effect and quick drug release in vitro, which are valuable to be studied further.

Comparative Study of the Character of Release in vitro between New MU-AN Ophthalmic Gel and the Old / 中国药师

Objective:To search the release in vitro of new MU-AN ophthalmic gel consist of ganciclovir instead of aciclovir is whether better than the Old. Methods:Using the content of ganciclovir and acyclovir as the index, taking the second oar method ( in Ch. P 2010), drug release in vitro test was investigated. Results:The character of drug release of new MU-AN ophthalmic gel was e-qual to the old, the rate of drug release was similar, The amount of drug release was the same. Both drugs met the requirements of clin-ical medication. The character corneal permeability of new MU-AN ophthalmic gel was better than the old. Gel matrix had no influ-ences on drug release, drug would be bring treatment effect after the way that it was released quickly then was dissolved in tear. Con-clusion:The drug release characteristics consistent with ophthalmic preparation requirements. The character of drug release of new MU-AN ophthalmic gel consist of ganciclovir instead of aciclovir is equal to the old, the time administer drug and interval time is gener-ally scientific, reasonable and feasible, providing the basis for the pharmacodynamics , toxicology and clinical study in the next step.

Research on Drug Release in Vitro of Sirolimus Liposome / 中国药房

OBJECTIVE:To investigate release characteristics of sirolimus liposome in vitro.METHODS:The concentration of sirolimus was determined by RP-HPLC.In vitro release rate of sirolimus liposome within 24 h was investigated by the reverse dialysis method with 20% ethanol 500 mL as medium.Release curve of sirolimus was fitted with drug release model equation.RESULTS:The linear range of sirolimus were 0.5～20 ?g.mL-1(r=0.999 8)with an average recovery of 99.42%(RSD=1.23%).At the first 4 hours of release,sirolimus liposome released rapidly with accumulative release rate of 50%.After that release rate of liposome was slowed down with accumulative rate of 80% in 24 h.The in vitro release curve conformed to the first order equation.CONCLUSION:Sirolimus liposome has delayed release capability,and in vitro drug release of sirolimus liposome is in concentration dependant manner.

Preparation and Quality Control of Doxycycline Hydrochloride Microspheres / 中国药房

OBJECTIVE: To prepare doxycycline hydrochloride microspheres and to establish a method for its quality control.METHODS: O/O emulsion solvent evaporation method was adopted to prepare doxycycline hydrochloride microspheres with poly (lactic-co-glycolic acid) (PLGA) as carrier.Light microscope was used to detect appearance and particle size of microspheres and UV spectrophotometry was applied to determine the loading rate and release rate of drug in vitro.RESULTS: Prepared microspheres are smooth and round with mean particle size of (49?6.9) ?m and span of 0.9.Average drug loading rate was (3.3?0.2) % and encapsulation efficiency was (52.4?3.2) % (n=3).Accumulative drug release reached 28% within 0.5 h with constant drug release lasting more than 30 days.CONCLUSION: Doxycycline hydrochloride microspheres preparation process is available and controllable in quality.

Drug Release Characteristics of Mu'an-Eye-Gel in Vitro / 中国药房

OBJECTIVE:To compare home-made mu'an-eye-gel(acyclovir plus honey) with commercial aciclovir(ACV)-eye-gel in releasing drug characteristics in vitro.METHODS:The in vitro drug release test was conducted by the third method of dissolution determination stated in Chinese Pharmacopeia together with bag filler method.The cumulative drug-releasing percentage and the acyclovir amount in mu'an-eye-gel versus ACV-eye-gel were determined by UV spec-trophotometry,and the accumulative releasing drug percentages of the two preparations were computed and their drug release behaviors w ere compared.RESULTS:The in vitro releasing behaviors of mu'an-eye-gel followed the Weibull kinetic equa-tion,however the vitro releasing behavior of commercial ACV-eye-gel followed the zero order kinetic equation,and the T80%and Q8 h had statistical significances between(mu'an-eye-gel:T80%=3.156?0.013(h),Q8 h=93.28?0.010(%);ACV-eye-gel:T80%=10.16?0.009(h),Q8 h=67.85?0.025(%)) 2 kinds of preparation.CONCLUSION:Mu'an-eye-gel is superior to the commercial ACV ophthalmic gel in both releasing velocity and accumulative drug release percentage.

Preparation of Levofloxacin Thermosensitive Ocular Gel and Study on Drug Release in Vitro / 中国药房

OBJECTIVE:To prepare the levofloxacin(LEF)thermosensitive gel for ophthalmic drug delivery,and to study the drug release in vitro.METHODS:Poloxamer407was used as themosensitive material for the LEF eye drop,the best con?centration of poloxamer in prescription was selected according to the temperature of gel,a novel membraneless model was used to study the drug release.RESUTS:The detected concentration of LEF was in the linear range of3～11?g/ml(r=0.9991,n=6),the recovery was99.62%;The best concentration of poloxamer in prescription was18%;Drug release followed zero-order kinetics,and the quantity of drug release was controlled by that of gel dissolution.CONCLUSION:The preparation is simple in method and easy to control in dosage,therefore it shows a promising future in development.

Studies on drug release in vitro and absorption in rat in vivo of ginsenoside Rd solid lipid nanoparticles / 中国药理学通报

Aim To investigate the release feature of ginsenoside Rd solid lipid nanoparticles (Rd-SLN) in vitro,and to clarify the difference in absorption of Rd-SLN from varied rat intestinal segments and pharmacokinetic properties in vivo. Methods Dialysis method was used to determine ginsenoside Rd release rate from nanoparticles in vitro. Perfusion method was used to study the intestinal absorption of Rd-SLN in rat. HPLC assay was established to determine the concentration of ginsenoside Rd in plasma. After intragastric administration,the concentrations of drug in rat blood at different time points were recorded to investigate the absorption and pharmacokinetics of Rd-SLN. Results The release of ginsenoside Rd from Rd-SLN was slowed down and presented the property of sustained release. There was no significant difference between the absorption rate of Rd-SLN and control solution in duodenum and jejunum. However,it was obviously different in ileum and colon. Comparing with other intestinal segments,significantly higher percentage of Rd-SLN was absorbed in colon. In Rd-SLN group,the concentration of ginsenoside Rd in blood was maintained,and the Cmax,MRT,AUMC,and AUC were all increased. Conclusions Rd-SLN possesses sustained-release effect. The colon is the preferable absorption site for Rd-SLN in intestinal tract. Rd-SLN can enhance the oral bioavailability of ginsenoside Rd.

Release in vitro of dexamethasone sodium phosphate from thermosensitive in situ gels / 第三军医大学学报

Objective To investigate the release feature of dexamethasone sodium phosphate from thermosensitive in situ gels in vitro. Methods Rotation rheometer was used to measure the changes of viscosity with temperature. The membraneless model was applied in assessing corrosion behavior of gel using a thermostatic shaker (50 r/min) at an amplitude of 2.5 cm, taking phosphate buffered solution (pH 7.2) as releasing media. The release behavior was investigated by HPLC on a C18 reverse column DiamonsilTM (250 mm?4.6 mm, 5 ?m). The mobile phase consisted of triethylamine solution-methanol-acetonitrile (38∶28∶34), pumped at 1.0 ml/min, and the detection wavelength was set at 242 nm. Results When the temperature was near to the sol-gel transition temperature, the viscosity rose suddenly. Taking dexamethasone sodium phosphate (2 ml, pH 7.2) as media, the gel dissolution and drug release rate followed the zero order kinetics, and the cumulative gel dissolution (Q1) and cumulative drug release (Q2) equations were Q1=0.8238t (r=0.999, P

Preparation of Psoralen Liposome Gel and its Drug-release Model in Vitro / 中国药房

OBJECTIVE:To prepare psoralen liposome gel and to conduct a quan titative investigation about its drug re?lease model in vitro.METHODS:Taken psoralen liposome gel that of the same concentration as the control group,the model of drug release in vitro of the testing group was evaluated by dialyzing method and the stability of its drug release after storage for3weeks at4℃was studied as well.RESULTS:Compared with the control group,the testing group showed significant slow-releasing and long-acting effects and the drug release followed the Higuchi(k=4.67%h -1/2 )diffusion model in the first3hours and a zero order drug release model(k=0.74%h -1 )3hours later;The drug release of the control group followed the Higuchi(k=7.18%h -1/2 )diffusion model of within24hours;The drug release model and the envelop rates of the testing group remained stable within the storage date.CONCLUSION:This preparation is characterized by slow drug releasing in vitro and good stability.