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Methotrexate (MTX) injection has a short half-life and significant toxic side effects. In order to overcome the demerits of MTX injection, MTX@COF was prepared for subcutaneous injection by loading MTX in crosslinked cyclodextrin metal-organic framework (COF) in this study. The cationic lipid material (2, 3-dioleoyl-propyl)-trimethylamine (DOTAP) was then coated on the MTX@COF surface by solvent evaporation. Different surface charge characteristics were observed in the coated MTX@COF@DOTAP with no significant change in particle morphology. The in vitro release behaviors of sustained-release particles were investigated in water and phosphate buffer (pH 7.4), and the in vivo release characteristics were evaluated for pharmacokinetics in rats. The in vitro release results showed that the cumulative release of MTX, MTX@COF and MTX@COF@DOTAP within 6 h was 92.70%, 36.31% and 18.19% in water, respectively; the cumulative release of MTX, MTX@COF and MTX@COF@DOTAP within 4 h was 90.82%, 79.37% and 58.30% in phosphate buffer, respectively; the results showed that MTX@COF can significantly delay the release of MTX, the modification to MTX@COF by DOTAP can further delay the release of MTX. Pharmacokinetic studies in rats showed that the mean retention time [MRT(0-t)] and the time to peak (Tmax) of the subcutaneous injection of MTX@COF@DOTAP group were significantly prolonged compared with the MTX@COF group and the MTX group. The area under the concentration-time curve [AUC(0-t)] of the MTX@COF@DOTAP subcutaneous injection group was 1.8 times high as that of the MTX group. In this study, MTX@COF@DOTAP particles had a certain sustained-release effect, and could prolong the bioavailability of MTX by subcutaneous injection, which provided a new idea for the development of new MTX dosage forms.
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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.
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Objective: To prepare Gualou-Xiebai intragastric floating pellets(18-24 mesh)by extrusion-spheronization method, and investigate their release characteristics in vitro. Methods: Using the floating time of pellets as indicator and the percentage of microcrystalline cellulose (MCC), octadecanol, hydroxypropyl methylcellulose- K4M (HPMC-K4M)and HPMC-K15M in the solid excipients of the prescription as affecting factors on the basis of single factor experiments, the formulation was optimized by star design-response surface optimization method. Taking the content of 3, 29-dibenzoyl karounitriol in the release medium as the index, the release rate of the pellets in vitro was determined and the release characteristics were explored. Results: The optimum prescription of these pellets was as follows: Gualou-Xiebai dry extract 25 g, MCC 6 g, octadecanol 11 g, HPMC-K4M 3 g, HPMC-K15M 11 g, 70% ethanol solution as wetting agent, and 40% polyvinylpyrrolidone(PVP-K30)solution as binder. The floating time in vitro of the pellets prepared by this prescription was 12 hours, and the cumulative release rate data fitted well with the first-order release model (r>0.97). Conclusion: The Gualou-Xiebai intragastric floating pellets prepared in this study had good floating property and sustained release effect, indicating that the preparation method is feasible.
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OBJECTIVE： To prepare Ursolic acid （UA）/Pluronic F127 （PF127）/TPGS-doxorubicin （DOX） mixed nanomicelles， and to characterize it and study its in vitro release behavior. METHODS： UA/PF127/TPGS nanomicelles were prepared by thin film hydration method. Using encapsulation efficiency of UA as index， combined with the results of single factor tests， L9（34） orthogonal test was used to optimize drug dosage of UA， molar ratio of PF127 to TPGS， hydration temperature and hydration volume， validation test was performed. On the basis of succinylated TPGS， TPGS-DOX was synthesized and mixed with UA/PF127/TPGS to prepare UA/PF127/TPGS-DOX mixed nanomicelles， the appearance， particle size and critical micelle concentration （PF127/TPGS） were investigated. The drug release behavior was examined by dialysis bag diffusion method. RESULTS： The optimal preparation technology of UA/PF127/TPGS nanomicelles was as follows as drug dosage of UA 8 mg， molar ratio of PF127 to TPGS 3 ∶ 7， hydration temperature 50 ℃， hydration volume 4 mL. Average encapsulation efficiency of UA in nanomicelles was 89.00％ （RSD＝0.43％， n＝3）. The prepared UA/PF127/TPGS-DOX mixed nanomicelles solution was clear with opalescence. The nanomicelles were spherical and uniform in size； average particle size was （115.00±9.42） nm； critical micelle concentration of PF127/TPGS （molecular ratio 3 ∶ 7） was 0.001 3％. The in vitro drug release of UA and DOX in the mixed nanomicelles was significantly slowed down， compared with raw materials or substance control. The drug release process of the two drugs in the nanomicelles conformed to Weibull equation. CONCLUSIONS： UA/PF127/TPGS-DOX mixed nanomicelles are successfully prepared with uniform particle size， good stability and good sustained-release effect.
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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.
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OBJECTIVE： To prepare Baicalin-loaded Polyethylene glycol-derivatized phosphatidylethanolamine （BAI@PEG-PE） nanomicelles， and to characterize it and study its cytotoxicity. METHODS： BAI@PEG-PE nanomicelles were prepared by film hydration method and their appearance characteristics were observed. The particle size， polydispersity index， Zeta potential， drug-loading amount and encapsulation efficiency of the nanomicelles were detected. Drug release of BAI raw material and BAI@PEG-PE nanomicelles in pH 7.4 phosphate buffer were compared within 1-84 h. Using coumarin 6 as fluorescent probe， the distribution of PEG-PE nanomicelles in H9c2 cardiomyocytes were observed. H9c2 cardiomyocytes were divided into model group， BAI raw material group and BAI@PEG-PE nanomicelles group. After treated with serum-free DMEM medium containing no or corresponding drugs for 0.5 h， isoproterenol was used to induce cardiomyocyte apoptosis. Nuclear morphology， cell apoptosis rate and protein expression of Bcl-2 and Bax were compared with among 3 groups. RESULTS： Prepared BAI@PEG-PE nanomicelles were uniform globular shape. The particle size was （16.7±0.8） nm， PDI was 0.11±0.01 and Zeta-potential was （－18.4±0.6） mV； drug-loading amount was （7.84±0.65）％， encapsulation efficiency was （85.7±4.9）％ （n＝3）. Accumulative release rate was 76.5％ within 84 h. BAI raw material was released completely within 24 h. PEG-PE nanomicelles could strengthen the intake of coumarin 6 in H9c2 cardiomyocytes， mainly gathering around mitochondria. Compared with model group， the apoptosis morphology of cardiomyocytes were improved significantly in BAI raw material group and BAI@PEG-PE nanomicelles group； apoptosis rate was decreased significantly； protein expression of Bcl-2 was increased significantly； protein expression of Bax was decreased significantly with statistical significance （P＜0.05 or P＜0.01）. Above effects of BAI@PEG-PE nanomicelles group were more significant （P＜0.05 or P＜0.01）. CONCLUSIONS： BAI@PEG-PE nanomicelles are prepared successfully， and show significant sustained-release effect and myocardial targeting， and can prevent cardiomyocyte apoptosis.
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OBJECTIVE: To prepare amoxicillin enteric-coated tablets and study the in vitro release properties. METHODS: The drug-containing pellets were prepared by extrusion-spheronization process. Taking the cumulative release at 15 min as the response value, the optimization test was performed using the common rotation combination design and the optimal formulation was validated. The drug-containing pellets were coated with Eudragit L30D-55 to prepare enteric-coated pellets. The effects of different coating weight gains on the release characteristics of enteric-coated pellets, different amounts of plasticizer on the release characteristics of enteric-coated pellets and tablets, and different hardness of tablets on the release characteristics of enteric-coated tablets were investigated by single factor method. RESULTS: The optimal formulation of the drug-containing pellets determined by response surface analysis method included 5% of croscarmellose sodium, 1.2% of polyoxyethylene 35 castor oil and 1% hydroxypropyl cellulose. The predictive value of the cumulative release at 15 min was close to the measured value. The coating weight gain of Eudragit L30D-55 should be about 20%, the amount of plasticizer should be 30% of solid content of Eudragit L30D-55, and the hardness of tablets was (130 ± 20) N. CONCLUSION: It is reasonable and reliable to optimize the formulation of drug-containing pellets by response surface analysis method. The enteric-coated tablets have good delayed release effect, and this product has the feasibility of industrial production.
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Objective To prepare salvianolic acid bioadhesive floating pellets; To prolong its residence time in vivo; To improve the oral bioavailability. Methods Salviae miltiorrhizae total phenolic acid adhering floating pellets were prepared by extrusion-spheronization. Chitosan, HPMC and carbomer were used as adherent material, stearyl alcohol was used as floating material and MCC as forming agent. The in vitro release of two adherent floating pellets were prepared and their bioavailability in rats were investigated. Results The results of in vitro release test showed that the salvianolic acid B in the blank pellets was completely released at 4 h, and the two adherent floating pellets prepared in vitro were released for 12 h. The results of pharmacokinetic studies in rats showed that after intragastric administration of salvianolic acid, salvianolic acid chitosan pellets and salvianolic acid HPMC pellets, Tmaxwere (12.00±2.74)min, (17.00±7.58)min and (27.00±12.55)min, respectively. The relative bioavailability of salvianolic acid chitosan pellets and salvianolic acid HPMC pellets were 177.08% and 172.03%, respectively. Conclusion Salvia total phenolic acid adherent floating pellets release slowly in vitro, and floating pellets can prolong the retention time in vivo and increase the oral bioavailability of salvianolic acid in rats.
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The multiple drug delivery system of components of traditional Chinese medicine is a system composed of multiple components and multiple units. According to the characteristics of each component, different drug delivery units are designed and combined to achieve the purpose of improving bioavailability and enhancing drug efficacy. In this study, supercritical extracts, phenolic acids, and polysaccharides derived from Angelica sinensis were examined as research objects, and a pellet-based vehicle was applied to construct a multiple drug delivery system for the treatment and chemoprevention of colitis and colorectal cancer. The extrusion-spheronization method was used to prepare pellets of Angelica polysaccharides which should be released in the stomach. The yield in 18-24 mesh and plane critical angle served as the index. The Box-Behnken design and the orthogonal design were used to optimize the formulation and parameters of pellets. According to a previous study, the colon specific pellets loading supercritical extracts and phenolic acid extracts were prepared by the optimized process. These two units of pellets were combined into the multiple drug delivery system of effective components of Angelica sinensis, and the quality evaluation and in vitro release study were conducted. The dynamic observation of pellets in mice was evaluated using small animal in vivo imaging system. The prescription of the Angelica polysaccharides gastric releasing pellets was:microcrystalline cellulose 6.5 g, polysaccharide 3.3 g, silica 0.2 g and 7 mL of 60% ethanol as wetting agent. The process parameters were as follows:extrusion rate at 75 r·min-1, rounding rate at 1 800 r·min-1, and rounding time for 3 min. Both in vivo and in vitro studies indicate that the prepared multiple drug delivery system of effective components of Angelica sinensis produced good release properties. The polysaccharide pellets could be rapidly released in the artificial gastric fluid and in the stomach. The colon specific pellets showed good targeting. They released little in the artificial gastric fluid within 2 hours, released less than 20% in the artificial intestinal fluid for 4 hours, and released more than 90% in artificial colon fluid for 6 hours.
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Objective To enhance the solubility and bioavailability of curcumin (CUR).Methods A novel curcumin nanoparticles were prepared.The CUR-PGD nanoparticles were prepared by the method of ultrasound precipitation combined with high-pressure homogenization using codendrimer PAMAM-co-0.25OEG (PGD) as stabilizer.The stability of CUR-PGD nanoparticles was measured in 0.9% sodium chloride solution,5% glucose, PBS and plasma.Results The drug loading capacity (DL%) of CUR-PGD nanoparticles was 41.2%, the solubility of CUR was increased to 1.5 mg·mL-1 (50 times of CUR bulk powder).The mean diameter of the nanoparticles was 438.0 nm with spherical morphology and the zeta potential was 41.4 mV.The nanoparticles was stable in 0.9% sodium chloride solution,5% glucose, PBS and plasma and there was no hemolytic phenomenon, which meant they were suitable for intravenous administration.The DSC and XRD spectra of CUR-PGD nanoparticles showed that the CUR was presented as crystal morphology in the nanoparticles.The CUR released from nanoparticles was detected in different releasing medium and presented obvious controlled release behavior.Conclusion PGD may be an effective stabilizer for the preparation of CUR-PGD nanoparticles and CUR-PGD nanoparticles are a promising drug delivery system for CUR application in clinic.
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Gastric adhesive-floating pellets for Bolo leaf phenols (BLP) were prepared by extrusion-spheronization method, with chitosan as skeleton bioadhesive material, and stearyl alcohol as help-bleaching agent to evaluate its in vitro adhesivity, floatability and in vivo retention situation, and investigate its in vitro release characteristics. The in vitro adhesivity and floatability were evaluated respectively by in vitro tissue retention method and visual observation method. The retention of pellets in rats was investigated by in vivo tissue retention method and in vivo imaging of small animals. In addition, the in vitro release of p-coumaric acid and caffeic acid as the index components in pellets were evaluated. Results showed that the in vitro adhesivity of the prepared gastric adhesive-floating pellets reached (73.2±3.4)%, and the pellets could float immediately in simulated gastric fluid for more than 12 h; the retention rate of adhesive-floating pellets in rats reached more than 40% after 6 h, while the retention rate of common reference pellets was decreased by 15% as compared with the gastric adhesive-floating pellets, with significant difference (P<0.01); the drug in vitro release time can reach more than 6 h, and the drug release behaviors were lined with Higuchi equation. In vivo and in vitro studies showed that, the gastrointestinal bioadhesive and floating pellets prepared in this study have good bioadhesivity, floatability and good sustained release characteristics.
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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.
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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.
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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.
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OBJECTIVE: To study the preparation technology of tamsulosion hydrochloride sustained-release capsules and investigate the release degree in vitro. METHODS: The pellets containing tamsulosin hydrochloride were prepeared in the fluid-bed using bottom gush medicine. Then, it was coated with ethylcellulose aqueous dispersion (surelease), and in the following procedures, water-based acrylic resin enteric system (Acryl-EZE®) was used as coating material, hydroxypropylmethylcellulose E6 (HPMCE6) was considered as porous agent by fluid-bed. Based on the release degree in vitro, prescription influence factors were evaluated, as well as drug releases curve was compared, according to the single factor experiment. RESULTS: The preparation technology referred in our research was available to make tamsulosin hydrochloride sustained-release capsules, and drug release curve of self-made sustained-release capsules was similar to the commercial one. Additionally, the products reproducibility of intra-batch and inter-batch was excellent. CONCLUSION: The tamsulosin hydrochloride sustained-release capsules prepared in this study exhibited ideal sustained-release characteristics in vitro. The formulation is reasonable and feasible. It is suitable for industrial production.
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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.
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To prepare pellets of supercritical fluid extraction (SFE) of Angelica Sinensis Radix by using the ionic crosslinking method, and the drug loading and encapsulation efficiency were used as the index to investigate the multiple factors which may impact the drug loading and encapsulation efficiency. Box-Behnken design and response surface analysis method were then taken to optimize the prescription of pellets and study the coating technology. Through the study on the release of pellets in vitro, an optimal coating technology and prescription of colon-specific pellets of Angelica Sinensis Radix SFE were selected and their colon targeting was evaluated. The optimal preparation parameters of pellets were determined as follows： 3% pectin; 4∶1 for pectin/lecithin; 4∶5 for pectin/SFE of Angelica Sinensis Radix; 4% zinc acetate solution as crosslinking agent, blending temperature 35 ℃, crosslinking temperature 35 ℃, crosslinking time 30 min; coating technology： coating material Eudragit FS 30D, 1.5% triethyl citrate and polyoxyethylene sorbitan monooleate（tween-80）, 1.2% monostearin and 15% coating weight gained. The colon-specific pellets of Angelica Sinensis Radix SFE prepared with optimized conditions were almost not released in simulated gastric fluid in 2 h, released less than 20% in simulated intestine fluid in 4 h, and released more than 90% in simulated colon fluid in 6 h, indicating that the colon-specific pellets of Angelica Sinensis Radix SFE had an excellent colon targeting property.
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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.
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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.
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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.