Preparation of Chelerythrine Solid Dispersion and Study on Its Physicochemical Properties and Antioxidant Activity / 中国药房

OBJECTIVE：To prepare Cheler ythrine （CHE） solid dispe rsion （SD），optimize the formulation technology ， characterize its preparation and investigate its in vitro antioxidant activity. METHODS ：The content of CHE in SD was determined by UV spectrophotometry. Based on single factor tests ，using the product yield as index ，using preparation method ，carrier material type，carrier material proportion （drug-carrier material mass ratio ）as factors ，the formulation technology of SD was optimized by L（9 34）orthogonal test and validated. Based on solubility and accumulative dissolution determination ，the product was characterized with thermal analyssis ，X-ray diffraction and scanning electron microscope. Using ascorbic acid as positive control ，in vitro antioxidant activity of the product was determined by DPPH method. RESULTS ：The linear range of CHE was 2.4-5.6 μg/mL； quantitation limit and detection limit were 0.066 9，0.022 1 μg/mL；RSDs of precision ，stability and reproducibility tests were all lower than 2％；recoveries were 97.50％-99.25％（RSD＜1％， n＝3）. The optimal preparation technology included using PEG 6000 as carrier material ，carrier material ratio of 1 ∶ 3， prepared by solvent method. Three batches of CHE-PEG-SD were prepared. Verification test results showed that the 话：0539-80311889。E-mail：zhenshengao@163.com accumulative dissolution of CHE-PEG-SD was （61.72 ± 0.67）％ at 15 min，and the yield was （99.04±0.83）％. The results of characterization showed that after CHE-PEG-SD prepared ， its solubility （3.725 mg/mL）and accumulative dissolution （61.25％，15 min）were higher than CHE raw material [ 0.098 mg/mL， 6.24％（180 min）]. The endothermic peak and crystal absorption peak moved or even disappeared compared with raw material and the carrier material ，and CHE was uniformly dispersed in the carrier material as an amorphous state. Results of in vitro antioxidation test showed that different concentration of CHE-PEG-SD showed certain ability of DPPH free radical scavenging ，and the IC 50 was 0.124 mg/mL，higher than 0.041 mg/mL of ascorbic acid. CONCLUSIONS ：Established content determination method is simple and accurate. The optimal SD formulation technology is stable and feasible. The solubility of prepared CHE-PEG-SD increases，and the dissolution in vitro increases，showing certain in vitro oxidation resistance.

Study on Dissolution in vitro of Cyclosporine Soft Capsules from 3 Domestic Manufacturers / 中国药房

OBJECTIVE： To investigate the similarity of in vitro dissolution curve between the generic drugs and the reference preparation （original drugs） of the domestic Cyclosporine soft capsules in 6 dissolution mediums. METHODS： The dissolution test was performed with paddle method. 2％ SDS water solution， 2％ SDS pH 1.2 hydrochloric acid solution， 2％ SDS water solution， 2％ SDS pH 4.5 acetate buffer solution， 2％ SDS pH 5.5 acetate buffer solution， 2％ SDS pH 6.8 phosphate buffer solution and 2％ SDS simulated gastric fluid were used as the dissolution medium， and the rotation speed was 50 r /min. HPLC method was used. The determination was performed on Agilent Eclipse XDB-C18 column with mobile phase consisted of acetonitrile phosphate solution （73 ∶ 27 ∶ 0.25，V/V/V），the flow rate was 1.0 mL/min. The detection wavelength was set at 226 nm， the column temperature was 60 ℃， and sample size was 20 μL. The dissolution curves in 6 medium were drawn and the similarity factor （f2） was used to investigate the similarity between the samples from 3 domestic manufacturers （5 batches） and a batch of original drugs. RESULTS： The linear range of cyclosporine was 5-250 μg/mL （r＝0.999 6-0.999 9）； RSDs of precision， stability （12 h） and reproducibility tests were lower than 2.0％ （n＝6 or 7）； the recoveries were 98.4％-99.7％ （RSD＜2.0％， n＝9）. The cumulative dissolution of 6 batches of samples within 15 min reached 85％ in 2％ SDS pH 1.2 hydrochloric acid solution and 2％ SDS simulated gastric juice. f2 of the dissolution curve of 5 batches of generic and original drugs of Cyclosporine soft capsules were 75， 45， 57， 42， 83 in 2％ SDS water solution and 44， 76， 38， 32， 76 in 2％ SDS pH 4.5 acetate buffer solution 76， 47， 49， 40， 79 in 2％ SDS pH 5.5 acetate buffer solution and 52， 49， 55， 48， 80 in 2％ SDS pH 6.8 phosphate buffer solution， respectively. CONCLUSIONS： There have differences in the similarity of the dissolution curve between the domestic generic and the original drugs of 5 batches of Cyclosporin soft capsule from 3 domestic manufacturers.

Optimization of preparation procedures of tanshinone-ⅡA /β-cyclodextrin inclusion complex and dissolution study of tanshinone-ⅡA in vitro / 中国中药杂志

In this paper, tanshinone-ⅡA (Tan-IIA)/β-cyclodextrin (β-CD) inclusion complexes were prepared by saturated aqueous solution method. Based on the single factor experiment, Box-Benhnken design and response surface method were utilized to optimize the preparation procedures of tanshinone-ⅡA/β-cyclodextrin inclusion complexes. The ratio of β-CD to Tan-ⅡA, experimental temperature and time were defined as independent variables, while the yield of the inclusion complexes, encapsulation efficiency and the generalized "normalized value" were set as the response value. In addition, the inclusion complexes were characterized by infrared spectroscopy (IR) and nuclear magnetic resonance (NMR). The results showed that optimum preparation conditions for Tan-ⅡA/β-CD inclusion complex were as follows: Tan-ⅡA/β-CD ratio of 1:7, the temperature of 48 ℃ and the time of 3 h. Under the optimized conditions, the encapsulation efficiency of Tan-ⅡA/β-CD inclusion complex was 84.75%. The Tan-IIA and β-CD inclusion complex can significantly improve the dissolution of Tan-ⅡA.

Effects ofⅠ,ⅡCrystal and Amorphous Forms of Lercanidipine Hydrochloride on the Preparation / 中国药房

OBJECTIVE:To study the effects of Ⅰ,Ⅱ crystal and amorphous forms of lercanidipine hydrochloride on the preparation,and provide theoretical basis for its development and consistency evaluation. METHODS:X-ray powder diffraction (XRD),infrared spectrophotometry(IR)and differential scanning calorimetry(DSC)were adopted to identify the 3 crystal forms of lercanidipine hydrochloride. XRD was used to compare the effects of crushing,grinding,pressing technology,wetting granula-tion,adhesive solvents(water,ethanol)and drying temperature(50,60,70℃)on stability of 3 crystal forms of lercanidipine hy-drochloride;the dissolution in vitro in water,hydrochloride,pH 4.5 acetate buffer,pH 6.8 phosphate buffer were compared among 3 crystal forms of Lercanidipine hydrochloride tablet. RESULTS:XRD showed both Ⅰ,Ⅱ crystal forms had characteristic diffrac-tion peak with inconsistent 2 θ values,amorphous had no characteristic diffraction peak;IR showed 3 crystal forms had different absorption intensity and absorption peak number;DSC showed Ⅰ,Ⅱ crystal forms had obvious endothermic peak in 194.6 ℃, 207.3 ℃,respectively,amorphous had obvious endothermic peak in 86.1 ℃ and exothermic peak in 299.8 ℃. Crushing,grinding, pressing and drying temperature had no effects on the stability of 3 crystal forms;water had no effect on the stability of crystal in wetting granulation,ethanol may cause the change of Ⅰcrystal form. Except for the comparison between Ⅰ,Ⅱ crystal forms in hydrochloride (f2=68),the dissolution f2 of 3 crystal forms in 4 kinds of medium were lower than 50. CONCLUSIONS:XRD, IR,DSC methods can identify the 3 crystal forms of Lercanidipine hydrochloride tablet. When preparing lercanidipine hydrochlo-ride by Ⅰcrystal form,wetting granulation should avoid using ethanol as a adhesive solvent,instead of water. Different crystal forms can affect the dissolution in vitro of prepared Lercanidipine hydrochloride tablet.

Study on in vitro release consistency between self-prepared Torasemide Sustained-Release Tablet and original preparation / 药物评价研究

Objective To establish a method for determining the dissolution oftorasemide sustained-release tablet in vitro and study the methodology of the determination.The consistency of the in vitro release behavior between self-prepared torasemide sustained-release tablet and original preparation were evaluated by constructed method.Methods HPLC method was applied to detect the cumulative release percentage of self-prepared torasemide sustained-release tablet and original preparation in five kinds of release media (water,0.1 mol/L hydrochloric acid solution,pH 4.5 acetate buffer,pH 6.8 phosphate buffer,and 0.1 mol/L hydrochloric acid solution turn to pH 6.8 phosphate buffer).Similarity factor (f2) was used to evaluate the similarity of release curves.Results There was a good linear relationship between the quality concentration of torasemide and peak area in the range of 1.0-12.0 μg/mL (r =0.9995).Results of precision and stability tests were good,and the RSDs for probational liquid were all lower than 2.0％.The average recovery of accuracy test was 100.04％,and RSD was 0.54％ (n =12).The homogeneity of within group of self-prepared preparation met the technical requirement,RSDs of each sampling points in six Dissolution Vessels were lower than 10.0％.The f2 factors of self-prepared torasemide sustained-release tablet and original preparation were 72,60,77,66,and 60 in five kinds of release media.Conclusion The method in the paper is suitable for the release test of torasemide,meanwhile,the self-prepared tablet shows consistent in vitro release behavior with that of the original preparation.

Preparation technology and physico-chemical characteristics of Olibanum ultramicro powders / 中草药

Objective: To optimize the technology and evaluate the influence of micronization on Olibanum physic-chemical characteristics and dissolution. Methods: The single factor test was employed to investigate the effect of the size and freezing time of common powder particle, the ratio of excipients, and grinding time on the yield of ultramicro powder; Additionally a comparative research between ultramicro powder and common powder was designed, including micromeritic properties (angle of repose, bulk density, tap density, and squeezing degree), effective components concentration [volatile oil, octyl acetate and 3-acetyl-11-keto-β-boswellic acid (AKBA)], and cumulative dissolution rate. Results: The optimal technology of ultramicro powder was as follows: the medicinal material was ground into fine powder, followed by 4 h freezing at -20℃ and 15 min superfine grinding with excipient and fine powder in ratio of 1:5; As the degree of smashing enhanced, the angle of repose of powders increased, bulk density and tap density decreased, and compressibility had a tendency of increase as flowability declined; The concentration of octyl acetate had an increased tendency and then decreased. While the concentration of octyl acetate in ultrafine powder prepared by optimal technology was the highest, the cumulative dissolution rate of AKBA in the ultramicro powder was higher than that in common powder. Conclusion: The application of optimal superfine pulverizing technique to Olibanum is feasible, and appropriate degree of micronization is helpful for the extraction and dissolution of effective components in Olibanum.

Study on the Formation Technology and Dissolution in vitro of Ibuprofen Dropping Pills / 中国药房

ABSTACT OBJECTIVE:To study the formation technology of Ibuprofen dropping pills and determine the dissolution in vitro. METHODS:Based on single factor test and with the spherical degree,drug-loading rate and pill weight variation as the evaluated indexes,response surface methodology was employed to screen the ratios of drug to matrix,drug solution temperatures and cryo-genic temperatures in the formation technology,and verification tests were conducted. The dissolution in vitro of the dropping pills prepared by the optimal technology was investigated and compared with that of the preparations sold in the market. RESULTS:The optimal formation technology of Ibuprofen dropping pills was as follows as the ratio of drug to matrix of 1∶6,drug solution temper-ature of 83 ℃ and cryogenic temperature of 7.3 ℃. In the verification tests,the self-made dropping pills demonstrated a spherical degree of 0.945 9,drug-loading rate of 99.82%,pill weight variation of 0.040 28 and drug-loading capacity of 30 mg/pill,with the actual comprehensive score of 0.972 5,deviating from the theoretical one (0.980 0) by 0.771 2%(RSD<1.5%,n=3). The dropping pills prepared had a dissolution rate of 25.36%at 5 min and an accumulated dissolution rate up to 90.12%at 30 min,sim-ilar with the Ibuprofen tablets sold in the market in drug release in vitro (f2=54.91),conforming to a first-order kinetic equation. CONCLUSIONS:The optimized formation technology is simple,stable,feasible and well reproducible,and the dropping pills which are prepared by such technology can release drug quickly.

Preparation of Genistein Solid Dispersion and Its Properties Study / 中国药房

OBJECTIVE:To prepare Geinstein (GEN) solid dispersion,and improve the dissolution rate of GEN in vitro. METHODS:Using PVP K30,PEG6000,and PEG4000 as carriers,GEN solid dispersion was prepared by solvent melting meth-od,and its dissolution in vitro was investigated. The structure of the solid dispersion was characterized by FTIR and DSC. RE-SULTS:GEN solid dispersion prepared with PEG4000 as carrier was better than those with other carriers in dissolution,and drug-carrier ratio (1:5) was the best. The results of DSC and FTIR showed that GEN in solid dispersion took amorphous form. CONCLUSIONS:GEN solid dispersion is prepared successfully and significantly improve the dissolution of GEN in vitro.

Preparation, optimization, and dissolution characteristics of curcumin nanoparticles lyophilized powder by antisolvent method / 中草药

Objective: Curcumin nanoparticles lyophilized powder (CNLP) were prepared by antisolvent method which was optimized using single factor method. In this process, acetone was used as solvent, deionized water was used as antisolvent, tween-80 was used as surfactant and mannitol was used as lyoprotectant. Methods: The main factors affecting the particle size of CNLP included the concentration of curcumin, volume ratio of solvent and antisolvent, dosage of surfactant, precipitation time, stirring speed, and dosage of lyoprotectant. The contrast experiments on dissolution in vitro was done between CNLP and raw curcumin powder. Results: The mean particle size of CNLP was (172.2 ± 4.6) nm; The Zeta potential of CNLP redissolving in water was (-19.7 ± 3.7) mV. The SEM graphs indicated the raw curcumin was in irregular and massive shape and its particle size was about 20 μm. The CNLP exhibited regular block structure and its particle size was about 170 nm which was obviously reduced compared with raw curcumin. The mean particle size of CNLP obtained from laser particle analyzer was in accord with the morphology of CNLP. The saturated solubility of CNLP was 41.32 times of raw curcumin powder in deionized water, 1.74 times in simulated gastric fluid and 4.11 times in simulated intestinal fluid through saturated solubility test, respectively. The dissolution rate of CNLP was 14.51 times of raw curcumin powder in water dissolution medium, 2.33 times in simulated gastric fluid and 44.79 times in simulated intestinal fluid through dissolution determination, respectively. Conclusion: The preparation process of CNLP using antisolvent method could improve the drawback of poor water solubility and enhance the bioavailability of curcumin.

Preparation and in vitro Dissolution of Ambroxol Hydrochloride Double-layer Tablets / 中国药师

Objective:To study the preparation technology of ambroxol hydrochloride double-layer tablets and evaluate the drug re-lease in vitro. Methods:The best technology was screened by orthogonal design, and the drug release in vitro was evaluated by UV spectrophotometry. Results:The drug release in vitro was in accordance with the corresponding standard. Conclusion:The preparation technology is simple and the quality is stable for industrial production.

Preparation and evaluation of silibinin solid dispersions in vitro / 第二军医大学学报

Objective: To prepare silibinin solid dispersion and measure its dissolution in vitro .Methods: Silibinin solid dispersions were obtained with urea, PVP and poloxamer188 as carriers by melting and coevaporation methods. Differential thermal analysis and powder X ray diffraction were used to determine the status of drug in carriers, and the dissolution characteristics in vitro were studied in simulated gastric juice. Results: In PVP silibinin solid dispersions drug was amorphous; in poloxamer188 silibinin solid dispersions, drug existed as fine crystal, while in urea silibinin solid dispersions most of silibinin existed as crystal, only a little as molecule. Poloxamer188 was the better carrier in improving the solution and dissolution rate of the drug. Conclusion: Poloxamer188 is a very useful carrier in improving the solubility and dissolution of silibinin. [

Preparation and dissolution characteristics of solid dispersion of ginsenoside Rg_3 / 中草药

Objective To prepare the solid dispersion of ginsenoside Rg3 with different carriers and measure their solubility and dissolution characterisitics. Methods The solid dispersion of ginsenoside Rg3 was prepared by the melted and dissolved methods with Poloxamer 188(F68), PVP k29/32, and PEG 6000 as carriers, respectively. The equilibrium solubility and dissolution characteristics of the solid dispersion in vitro were measured by HPLC. The existing state of ginsenoside Rg3 in the solid dispersion was identified by the differential scanning calorimetery. Results The ginsenoside Rg3 was completely dispersed in carrier and formed a mixture with carriers. The solubility and dissolution rates of all solid dispersion were increased obviously. Conclusion The solid dispersion of ginsenoside Rg3 with Poloxamer 188 as carriers is better on improving dissolution and solubility than those with PVP and PEG 6000 as carriers.

Study on dissolution of three active components in Shexiang Baoxin Pill / 中成药

AIM: To study the dissolution of ginsenoside Rb1,cinnamic acid and borneol in traditional Chinese medicine Shexiang Baoxin Pill(Moschus,extract of Radix et Rhizoma ginseng,Calculus Bovis artifactus,Cortex Cinnamomi,Styrax,Venenum Bufonis and Borneolum syntheticum). METHODS: The in vitro dissolution of active components in Shexiang Baoxin Pill was performed with paddle method. HPLC was used for determination of ginsenoside Rb1 and cinnamic acid,and GC for borneol. RESULTS: The analytic method above was easy to carry out,the requirement of the specificity,accuracy,precision and stability could meet the needs of experiment well; the dissolution time T50 and Td of ginsenoside Rb1,cinnamic acid and borneol were 30. 90,33. 79 min,29. 73, 37. 11 min and 42. 38,48. 51 min respectively. CONCLUSION: The dissolution rate of three active components from Shexiang Baoxin Pills was fast and the analytic methods established in this study could be used to evaluate the quality of the preparation.

In vitro evaluation of indirubin self-emulsifying drug delivery system / 中成药

AIM: To prepare indirubin self-emulsifying drug delivery system(SEDDS) and evaluate it in vitro. METHODS: The criteria of SEDDS formation was studied and indirubin SEDDS preparation optimized with triangle phase diagram.In order to investigate self-emulsifying ability,the time of self-emulsifying,particle size of emulsion and the dissolution of indirubin in vitro were determined. RESULTS: The best formulation of SEDDS was made up of labrasol-peceol-transcutol P(85∶10∶5),which served as oil phase,emulsifier and assistant emulsifier,respectively.The selected formulation could completely emulsify in 5 min and the particle size was about 100 nm.As compared with indirubin suspension,SEDDS could improve drug dissolution significantly. CONCLUSION: SEDDS can give rise to the dissolution increase of slightly soluble drug in water in vitro.

Preparation and dissolution of solid dispersion of angelica dahurica coumarins / 中成药

AIM: To prepare the solid dispersions of angelica dahurica coumarins and measure their dissolution characteristics. METHODS: The solid dispersions were obtained by using the melted and dissolved methods with PEG6000, PVP and poloxamer188 as carriers respectively.The existing state of the coumarins in the solid dispersions were identificated by the differential scanning calorimetery. The dissolution characteristics of the solid dispersions in vitro were analyzed by HPLC method under the chromatographic conditions with ThermoC_(18)(150 mm?4.6 mm,5 ?m) as analytial column and methanol/water(70∶30)as mobile phase,using imperatorin as testing index. RESULTS: The melted and dissolved methods can be used to prepare the solid dispersions.The coumarins were completely dispersed in carrier and formed an euctics mixture with the carrier.The dissolution rates of all solid dispersion were increased obviously. CONCLUSION: The solid dispersion prepared with PVP can increase the solubility and dissolution of the coumarins.

Preparation of Rifampicin Suppositories and Solubility Determination / 中国药房

OBJECTIVE: To prepare rifampicin suppositories and to determine its dissolution in vitro. METHODS: Rifampicin suppositories were prepared with gelatin and glycerine as base material, the dissolution of rifampicin suppositories was determined by UV spectrophotometry and which were compared with rifampicin capsules sold in the market. RESULTS: The linear range of rifampicin was 10.0～60.0?g?mL-1(r=0.9 999), and the average recovery was 99.87%(RSD=0.42%, n=6). The dissolutions of rifampicin suppositories and rifampicin capsules in vitro at 45min were(89.9?0.97)% and(79.8?1.14)%, respectively. CONCLUSION: Rifampicin suppositories were simple in preparative method, well-formed, low in cost, and with high dissolution in vitro.

The Study of the Sustained Release Ketoprofen Tablet / 第二军医大学学报

Ketoprofen is widely used as non-steroidal anti-inflammatory drug. A potential sustained release ketoprofen tablet formulation was designed by orthogonal experiment on formulations composed of differential common excipients and homemade polymerides, and was screened by dissolution in vitro. The dissolution rate (%) of the ketoprofen tablet in simulated intestinal fluid was 16.6, 26.7, 42.2, 63.6, 83.1, 93.4, at 30min, 1, 2, 4, 6, 8 h, respectively. The plasma ketoprofen concentrations in six male volunteers were assayed after administration of a single oral dose (100 mg) of the sustained release tablet. It was found that the tablet formulation screened in vitro had sustained release effect in vivo too. This study suggests that there was a close correlation between the dissolution of sustained release ketoprofen tablet in vitro and the percent of dose absorbed in vivo, and the correlation coefficient was 0.9689. The influence of tablet hardness on the release rate of ketoprofen was also observed..