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Objective: To synthetize the new-type GO-DEX-β-CD/DOC and Fe3O4/GO-Na/DOC inclusion compound, and study its high-efficiency loading, sustained-release and permeability as transdermal delivery for docetaxel (DOC) composites. Methods: The concentration of DOC was determined by high efficiency liquid chromatography. The high-efficiency loading, sustained-release and permeability as transdermal delivery of GO-DEX-β-CD/DOC and Fe3O4/GO-Na/DOC were studied, and the encapsulation efficiency and drug loading of them were determined by centrifugation. The GO-DEX-β-CD/DOC and Fe3O4/GO-Na/DOC were applied onto the female mice skin in vitro and in vivo to develop the permeability of them. Results: The encapsulation efficiency and drug loading of Fe3O4/GO-Na/DOC were higher than GO-DEX-β-CD/DOC, and its slow release property and permeability as transdermal delivery were better. The results showed that the accumulation permeation amount was (22.512 ± 0.715) μg after Fe3O4/GO-Na/DOC being applied over 90 h, DOC concentration in skin reached a peak at 15 min by the application of Fe3O4/GO-Na/DOC. After 5 h of administration, DOC concentration in the blood of female mice reached (76.886 ± 1.232) μg/mL. Conclusion: The preparation techniques of Fe3O4/GO-Na/DOC was feasible with better sustained release and transdermal effect, which had a promising application prospect.
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OBJECTIVE： To establish a method for content determination of indapamide （IDP）-β-cyclodextrin （β-CD） inclusion compound， optimize the preparation technology， carry out phase identification and in vivo release study of it. METHODS： UV spectrophotometry was used to determine the content of IDP in IDP-β-CD inclusion compound. IDP-β-CD inclusion compound was prepared by the solution-stirring method and the preparation technology was optimized by the orthogonal experiment using inclusion rate as index. The inclusion rate and drug-loading rate were compared between different drying methods. Phase identification of IDP-β-CD inclusion compound was verified by IR and DSC. The cumulative release rate of inclusion compound was tested by in vitro experiment. RESULTS： The linear range of concentration of IDP was 2.0-14.0 μg/mL （r＝0.999 7）. The quantitative limit and detection limit were 0.204， 0.067 μg/mL， respectively. RSDs of precision， stability and repeatability tests were all less than 2％. The recoveries range was 98.8％-101.8％（RSD＝1.10％，n＝6）. The optimum technology conditions were as follows the molar ratio of β-CD to IDP was 3 ∶ 1， the inclusion time was 3 h， and the stirring speed was 300 r/min. Average inclusion rate of IDP-β-CD inclusion compound was 72.81％. IR and DSC analysis showed that IDP and β-CD formed inclusion compound through physical interaction. After spray drying， the inclusion rate and drug-loading rate of IDP-β-CD inclusion compound were （60.96±0.25）％ and （4.18±0.12）％. After freeze-drying， the inclusion rate and drug-loading rate of IDP-β-CD inclusion compound were （77.31±0.51）％ and （5.31±0.27）％. Accumulative release rates of IDP， IDP-β-CD inclusion compound （by freeze-drying and spray drying） were 37.2％， 42.5％ and 81.9％ within 12 h， respectively. Compared with IDP raw material， accumulative release rate of IDP-β-CD inclusion compound increased significantly after spray drying. CONCLUSIONS： Established method is simple and accurate. The optimal preparation technology of inclusion compound is stable and feasible. IDP-β-CD inclusion compound is prepared successfully. The inclusion compound prepared by spray drying shows higher release rate.
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OBJECTIVE: To observe effects of β-cyclodextrin inclusion on tanshinone ⅡA in the degradation which in rat intestinal flora in vitro. METHODS: Culturing the tanshinone ⅡA and inclusion compound separately with incubation buffer of rat intestinal flora, sampling after 06121824 h. Extracting the sample then analyze content by HPLC. RESULTS: The tanshinone ⅡA is degraded obviously by rat intestinal flora in vitro and degradation speed became slower after forming the inclusion compound. After degrading 18 h, the declining proportion of tanshinone ⅡA concerntration which in tanshinone ⅡA group and mixture of tanshinone ⅡA with β-cyclodextrin group reached (74.23±2.32)% and (80.23±1.14)% while (47.45±4.01)% in β-cyclodextrin inclusion group. CONCLUSION: The tanshinone ⅡA is degraded almost completely by rat intestinal flora in vitro during 24 h, the degradation speed will be slower while forming the inclusion compound.
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AIM To prepare the thermosensitive intestinal gels of Houttuynia cordata Thunb volatile oils hydroxypropyl-β-cyclodextrin (HPCD) inclusion compound.METHODS For the gels prepared by cold dissolving method,poloxamer 407 consumption and poloxamer 188 consumption were taken as influencing factors,together with phase transition temperature as an evaluation index,central composite design-response surface method was applied to optimizing the formulation.With 2-undecanone as an index component,the gels' dissolution rate and in vitro release rate were investigated by non-membrane dissolution method and dialysis bag method respectively,whose stability was then evaluated by high temperature (40,60 ℃),low temperature (4 ℃),strong light [(4 500 ±500) 1x] and acceleration (three months) tests.RESULTS The optimal conditions were determined to be 20.61％ for P407 consumption and 3.03％ for P188 consumption,the phase transition temperature was 36.5 ℃.Within the time range of 30-150 min,the HPCD inclusion compound gels exhibited higher accumulative dissolution rate than the volatile oils gels,which tended to be consistent in 150-210 min,but the former exhibited higher accmulative release rate (0-50 h) than the latter all the time.The obtained gels showed good stability at low temperature,whose appearance,characteristic (except for high temperature) and pH were stable at high temperature,strong light and acceleration with obviously decreased 2-undecanone content.CONCLUSION The thermosensitive intestinal gels of Houttuynia cordata Thunb volatile oils HPCD inclusion compound should be stored at low temperature (4 ℃).
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OBJECTIVE: To prepare Formononetin (FMN) inclusion compound liposome and evaluate its quality. METHODS: FMN inclusion compound liposome was prepared by film dispersion method. The morphology, particle size, Zeta potential, encapsulation efficiency and in vitro release properties were studied. RESULTS: The particle size, Zeta potential and encapsulation efficiency of prepared FMN inclusion compound liposome were (255. 34 ± 12. 87) nm, (25. 32 ± 3. 51) mV, (81. 63 ± 0. 79)％, respectively (n=3). The 24 h accumulative release rate of prepared FMN inclusion compound liposome was 56. 12％. CONCLUSIONS: FMN inclusion compound liposome with good sustained-release effect is prepared successfully and in line with related quality standard.
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Objective: To prepare 1% voriconazole ( VCZ) sulfonated butyl ether- β-cyclodextrin ( SBE-β-CD) inclusion com-pound eye drop and study the quality. Methods: VCZ SBE-β-CD inclusion compound was prepared with the molar ratio of VCZ to SBE-β-CD of 1 :1. Sodium chloride was used as the osmotic pressure regulator and benzalkonium bromide was employed as the pre-servative in the preparation of VCZ SBE-β-CD inclusion compound eye drop. The appearance, pH value, content stability and irritation of the eye drop were studied as well. Results:The eye drop was colorless and transparent solution with the pH value of 6. 44 ± 0. 20, 6. 50 ± 0. 15,6. 48 ± 0. 22 the osmotic pressure of (320 ± 4. 62),(316 ± 2. 88),(322 ± 2. 60)MOsm and the VCZ content of 1. 02% g ·ml-1 . The results of accelerated testing and long-term testing showed no notable changes in the quality indices. The eye drop exhibi-ted no significant irritation to the rabbit eyes. Conclusion:VCZ SBE-β-CD inclusion compound eye drop shows the properties of high VCZ content, stable quality and promising safety in eye application, which is worthy of further studies.
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Objective: To prepare voriconazole (VCZ) sulfonated butyl ether-β-cyclodextrin (SBE-β-CD) inclusion compound and study the properties in vitro.Methods: VCZ SBE-β-CD inclusion compound was prepared respectively by a stirring method, an ultrasonic method and a grinding method, and the one with the highest inclusion rate and inclusion compound yield was chosen as the final preparation method.The formula and preparation process were optimized by an orthogonal design.The inclusion compound was identified by differential scanning calorimetry and solubility determination, and the in vitro dissolution was determined as well.Results: The stirring method had the highest inclusion rate and inclusion compound yield, and the optimal preparation and formula conditions were as follows: the inclusion temperature was 25℃, the stirring time was 4 h and the amount ratio of VCZ to SBE-β-CD was 1∶1.After the optimization, the inclusion rate was (86.14 ± 0.69)%, and the yield of inclusion compound was (97.11 ± 0.31)%.After the inclusion, the characteristic peak of VCZ disappeared and the solubility of VCZ increased significantly.Compared with those of VCZ, the dissolution rate and amount of VCZ inclusion compound both increased notably.Conclusion: VCZ SBE-β-CD inclusion compound can be prepared by the stirring method, which lays foundation for the further studies on VCZ eye drop.
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AIM To prepare the hydroxypropyl-β cyclodextrin inclusion compound of volatile oil from Houttuyniae Herba.METHODS In the content determination of volatile oil by GC,2-undecanone was taken as a reference substance,and inclusion rate and drug loading were calculated.After the determination of optimal method for preparing the inclusion compound among techniques of mixing,grinding and ultrasonic methods.the preparation process was optimized by orthogonal test with ratio of volatile oil to hydroxypropyl-β cyclodextrin,inclusion temperature,mixing speed and inclusion time as influencing factors,and inclusion rate and drug loading as evaluation indices.The characterization was performed by TLC,infrared spectroscopy and differential scanning calorimetry.Then high temperature,high humidity and strong light tests were applied to investigating the inclusion compound stability.RESULTS Mixing method brought forth the maximal yield,inclusion rate and drug loading for the inclusion compound.And under the optimal conditions of 1 ∶ 25 for ratio of volatile oil to hydroxypropyl-β cyclodextrin,50 ℃ for inclusion temperature,420 r/min for mixing speed,and 80 min for inclusion time,the inclusion rate and drug loading were identified to be 77.35％ and 4.48％,respectively.The obtained inclusion compound was found to be white powder with loose texture and significantly increased solubility,the in vitro accumulative release rate reached 80.85％.Deliquescence and agglomeration,as well as obviously decreased inclusion rate and drug loading,were observed at a relative humidity of more than 75％,despite the good stability at high temperature (60 ℃) and strong light (3 000 lx),and yet the rehydration character was good.CONCLUSION It is possible that the hydroxypropyl-β cyclodextrin inclusion compound of volatile oil from Houttuyniae Herba generates a new phase rather than a simple mixture,which should be kept dry and sealed at the time of storage.
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OBJECTIVE:To prepare paeonol-HP-β-cyclodextrin (PAE-HP-β-CD) inclusion compound and to optimize its pre-scription technology. METHODS:PAE-HP-β-CD was prepared by freeze drying method and validated. Using inclusion rate as in-dex,main drug-accessory ratio,inclusion time,inclusion temperature and stirring speed as factors,the preparation technology was optimized by central composite design-response surface methodology. RESULTS:Prepared PAE-HP-β-CD underwent phase transfor-mation. The optimal inclusion technology was as follows as main drug-accessory ratio of 3.39∶1,inclusion temperature of 50 ℃, inclusion time of 3.2 h, stirring speed of 350 r/min. Relative error between measured value (87.46%) and predicted value (89.12%) of inclusion rate was 1.86%(n=6). CONCLUSIONS:PAE-HP-β-CD inclusion compound is prepared successfully, and its prescription technology is stable and feasible.
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Objective:To study the effects of voriconazole sulfonated butyl ether-β-cyclodextrin inclusion compound(VCZ-SBE) eye drop on fungal keratitis (FK) in rabbits. Methods:Aspergillus fumigatus was used for the establishment of FK model in rabbits. Totally 48 healthy rabbits were divided into four groups. The 12 right eyes in group A were inoculated with Aspergillus fumigatus with-out any treatment. The 12 right eyes in group B were inoculated with Aspergillus fumigatus,and then treated with 0.5% VCZ-SBE eye drop,those in group C were inoculated with Aspergillus fumigatus,and then treated with 1.0% VCZ-SBE eye drop,and those in group D were inoculated with Aspergillus fumigatus,and then treated with 0.5% fluconazole eye drop. The cornea of normal left eyes in the four groups was used for the blank control. Ulcer grading was performed for all the eyes in 0,1,4,7 and 14 d after the successful es-tablishment of FK model. Every 3 rabbits were sacrificed in 1,4,7 and 14 d,and then the cornea was obtained to evaluate the infiltra-tion degree of inflammatory cells and the invasion depth of hyphae into cornea. Results:After the successful establishment of FK mod-el,the ulcer grading among the groups showed no significant difference(P>0.05). Respectively after the 7,4 and 14-day treatment, the ulcer grading in group B,C and D was notably lower than that in group A (P<0.05). After the 4,7 and 14-day treatment,the ulcer grading,infiltration depth and necrosis degree in group C were all lower than those in group B and D(P<0.05),and after the 7 and 14-day treatment,those in group B were lower than those in group D(P<0.05). Conclusion:Compared with fluconazole eye drop at the same concentration,VCZ-SBE inclusion compound eye drop can decrease the ulcer grading of FK and reduce the infiltration depth in a concentration-dependent manner.
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Objective:To prepare mesalazineβ-cyclodextrin inclusion compound and observe its properties. Methods:The struc-ture was characterized by UV, IR and DSC. The inclusion process of mesalazine andβ-cyclodextrin was simulated using molecular doc-king technique. The solubility and dissolution of inclusion compound were determined. Results:UV, IR and DSC were used to deter-mine the formation of inclusion complex. The inclusion ratio was 1: 1 and the phase solubility diagram was AL type. The solubility of inclusion compound in deionized water (25 ℃, pH 7. 0) was 7. 8 mg·ml-1 . The preparation of mesalazine β-cyclodextrin inclusion compound could significantly increase the dissolution rate and solubility of mesalazine. Conclusion:The prepared mesalazineβ-cyclo-dextrin inclusion compound can obviously improve the poor water solubility and dissolution of mesalazine.
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Objective To optimize the extraction of volatile oil from Qingjie Granules and process of inclusion compound of beta-cyclodextrin. Methods Water Distillation was used for extraction. Extraction time, grinding degree, and the amount of water were set as inspection factors, and volatile oil volume was set as the evaluation index to inspect extraction process of volatile oil from Qingjie Granules. With inclusion rate as the evaluation index, the single factor test and the Box-Behnken combined with the response surface method were used to choose the optimum inclusion process. Results The optimum extraction process for Schizonepetae Herba, Saposhnikoviae Radix and Forsythiae Fructus coarse powder should be with 10 times amount of water, extracting 3 h. Inclusion method should be saturated water solution method, and the inclusion process of volatile oil as feed and beta-cyclodextrin inclusion ratio was 1:12; the temperature was 40 ℃; inclusion time was 3.5 h. By means of TLC, UV and IR spectra, the formation of the inclusion compound of volatile oil in clear solution particles was preliminarily proved. Conclusion The optimum extraction and inclusion process of volatile oil from Qingjie Granules are stable and feasible, which can be used in industrial production.
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Objective: To prepare 1% voriconazole ( VCZ) sulfonated butyl ether- β-cyclodextrin ( SBE-β-CD) inclusion com-pound eye drop and study the quality. Methods: VCZ SBE-β-CD inclusion compound was prepared with the molar ratio of VCZ to SBE-β-CD of 1 :1. Sodium chloride was used as the osmotic pressure regulator and benzalkonium bromide was employed as the pre-servative in the preparation of VCZ SBE-β-CD inclusion compound eye drop. The appearance, pH value, content stability and irritation of the eye drop were studied as well. Results:The eye drop was colorless and transparent solution with the pH value of 6. 44 ± 0. 20, 6. 50 ± 0. 15,6. 48 ± 0. 22 the osmotic pressure of (320 ± 4. 62),(316 ± 2. 88),(322 ± 2. 60)MOsm and the VCZ content of 1. 02% g ·ml-1 . The results of accelerated testing and long-term testing showed no notable changes in the quality indices. The eye drop exhibi-ted no significant irritation to the rabbit eyes. Conclusion:VCZ SBE-β-CD inclusion compound eye drop shows the properties of high VCZ content, stable quality and promising safety in eye application, which is worthy of further studies.
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Objective:To prepare mesalazine hydroxypropyl-β-cyclodextrin ( MSZ-HP-β-CD) inclusion complexes and observe the properties. Methods:The inclusion complexes were prepared by a stirring method and the content of MSZ was determined by HPLC. The preparation technology was optimized by orthogonal test with the inclusion rate and the yield of inclusion complexes as the indices. The inclusion complexes were identified respectively by ultraviolet ( UV) spectrometry, X-ray diffraction ( XRD) and solubility. The dissolution rate was investigated. Results: Using the stirring method, the optimum preparation process was as follows: the inclusion temperature was 35 ℃, the ratio of MSZ to HP-β-CD was 1∶ 4 ( mg/g) , and the inclusion time was 3 h. The average inclusion rate of the complexes was 96. 28%, and the yield was 97. 87%. The identification results showed that the freeze-dried powder was inclusion complexes. Compared with that of MSZ, the dissolution of MSZ- HP-β-CD inclusion complexes was notably enhanced. Conclusion:The prepared MSZ-HP-β-CD with optimized technology has good reproducibility and stable technology, which can obviously improve the dissolution of MSZ.
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Objective:To prepare thermosensitive liquid suppositories of mesalazine( MSZ) HP-β-CD complex and study the in vitro properties. Methods:Poloxamer 407 (P407) and poloxamer 188 (P188) were used as the thermosensitive polymers to load MSZ HP-β-CD complex to prepare the thermosensitive liquid suppositories. The viscosity, gel strength, bioadhesion,in vitro gel erosion and drug release of MSZ HP-β-CD complex were compared with those of MSZ liquid suppositories. Results: Compared with that of MSZ liquid suppositories, the gel temperature of MSZ HP-β-CD complex liquid suppositories was stable, while the viscosity, gel strength and bioadhesion of MSZ HP-β-CD complex liquid suppositories were increased significantly. The in vitro gel erosion was not affected by MSZ HP-β-CD complex, while the drug release was notably enhanced. The drug release and gel erosion showed a good linear relation-ship. Conclusion:MSZ HP-β-CD complex liquid suppositories show good gel temperature, viscosity, gel erosion and bioadhesion, and the in vitro release rate is faster than that of MSZ liquid suppositories.
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Objective To optimize the preparation of liensinine HP-β-CD inclusion compound; To investigate its dissolution performance in vitro. Methods The inclusion compound of liensinine was prepared by using saturated water solution method; the cumulative dissolution (45 min) was used as an indicator and Box-Behnken design was adopted to evaluate the influence of feed ratio, mixing time and inclusion temperature on preparation process. Results were analyzed by multiple linear and binomial fitting; response surface methodology was used to screen the optimal inclusion process; predictive parsing and verification experiment were conducted; SEM, DSC, IR, and XRD were applied for the structural characterization of inclusion compound of liensinine. Results The optimal preparation process was: HP-β-CD was 4.5 times the amount of liensinine feeding amount; mixing time was 3.7 h; inclusion temperature was 52 ℃. HP-β-CD inclusion compound of liensinine formed. Conclusion Optimal inclusion process is stable and feasible, which can significantly improve the dissolution of liensinine and increase its bioavailability.
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Objective:To study the effect of mesalazine hydroxyl-propyl-β-cyclodextrin inclusion compound ( MSZ-HP-β-CD) liq-uid suppositories on ulcerative colitis ( UC) in rats. Methods:Dextran sulfate sodium was used to induce UC in rats. The marketed MSZ suppositories were applied as the positive control, and the changes in morphology and histopathology of the UC rats were observed after the treatment with MSZ-HP-β-CD liquid suppositories. Results:The results of morphology study showed that CMDI was decreased in the two MSZ preparation groups when compared with that in the model group (P<0. 01), and that in MSZ-HP-β-CD liquid supposi-tories group was the lowest (P<0. 05). The results of histopathology study showed that with the treatment of the marketed MSZ sup-positories and MSZ-HP-β-CD liquid suppositories, the ulcer and damage were improved, and the improvement in the MSZ-HP-β-CD liquid suppositories group was more significant. Conclusion: MSZ-HP-β-CD liquid suppositories exhibit better effect on UC in rats when compared with the marketed MSZ suppositories, which is worthy of further studies.
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Objective:To optimize the preparation technology of ketoconazole and miconazole nitrateβ-cyclodextrin inclusion com-pound. Methods: The weight ratio of β-cyclodextrin to ketoconazole, inclusion temperature and inclusion time as the testing factors, the optimal inclusion technology was screened by orthogonal experiments. Results:The optimum inclusion conditions were as follows:the weight ratio of β-cyclodextrin to ketoconazole was 8 ∶1, the inclusion temperature was 50℃, and the ultrasonic time was 50 min. Conclusion:The optimized β-cyclodextrin inclusion process is simple and convenient to carry out.
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Objective To optimize the preparation technology ofCangai volatile oil dextrin inclusion compound/ in situ nasal thermosensitive gel by the central composite design-response surface method.Methods In the design, the investigation factors were the amounts of poloxamer 407 and poloxamer 188, and the evaluation index was the gel temperature. Quadratic models were used to evaluate the mathematic relation between the evaluation index and two investigation indexes to identify the optimum prescription, and then the optimum prescription was verified. Results According to the quadratic models, it was found that there was reliable quantitative relation between the evaluation index and two investigation indexes, among which the optimum dosage was 19.37% for poloxamer 407 and 2.73% for poloxamer 188.Conclusion The optimum model ofCangai volatile oil dextrin inclusion compound/ nasal thermosensitive gel can be obtained from central composite design-response surface method based on quadratic models. This method is reliable and feasible, which can realize the prescription optimization of the in situ gel.
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Objective: To study the optimized technology of inclusion for the volatile oil of Caryophylli Flos with β-cyclodextrin polymer (β-CDP) microsphere. Methods β-CDP Microsphere was prepared by saturated peroxide solution. The study was carried out with uniform design to optimize the best inclusion processing conditions and inclusion compound was to characterize its structure. Results The best condition of the optimized technology of inclusion for the volatile oil of Caryophylli Flos with β-CDP microsphene was as follow: the volatile oil of Caryophylli Flos (mL)-β-CDP microsphere (g) was 1:1; inclusion temperature was 35°C; clathration time was 1 h; ethyl alcohol could be ignored. The package method is successful by characterizing structure. Conclusion: The inclusion compound of β-CDP has high rate and the inclusion process is reasonable and feasible.