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Four salts of ticagrelor, ticagrelor-3,5-dinitrobenzoic acid, ticagrelor-pyrazinamide, ticagrelor-D-proline and ticagrelor-L-proline were prepared by solvent suspension and liquid-assisted grinding to improve the solubility of ticagrelor. The compounds were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy, elemental analysis, and the intermolecular salt-bonding forces were analyzed. The equilibrium solubility of salts and pure drug in hydrochloride buffer pH 1.2 and phosphate buffer pH 6.8 were measured by high-performance liquid chromatography. Ticagrelor was salted with 3,5-dinitrobenzoic acid, pyrazinamide, D-proline, L-proline all in a stoichiometric ratio of 1∶1; with the exception of ticagrelor-D-proline, the solubility of the other three salts provided significantly improved solubility in hydrochloride buffer pH 1.2, and the equilibrium solubility of ticagrelor-3,5-dinitrobenzoic acid was increased by approximately 1.7 folds as compared to pure drug. Salt-forming technology is convenient and can improve the solubility of ticagrelor.
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OBJECTIVE: To prepare a novel naringenin co-crystal to improve the poor water solubility of the compound. METHODS: Solvent volatilization method was used to prepare naringenin nicotinamide co-crystal, with ethyl acetate as solvent. It is characterized by the technology of infrared spectroscopy (IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), scanning electron microscopy (SEM) and other techniques. RESULTS: By measuring the equilibrium solubility of different pH solutions, it was found that the naringenin nicotinamide co-crystal has a significantly improved equilibrium solubility compared with naringenin. CONCLUSION: This method can improve the solubility of naringenin, which is simple and easy, and lays the foundation for further study of naringenin co-crystal.
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OBJECTIVE: To introduce the basic procedure and technical requirements of equilibrium solubility experiments and provide reference for design and conduct of equilibrium solubility experiments scheme. METHODS: The concept and influence factors of solubility, principle and determination method of solubility experiments, equilibrium solubility project of world health organization were analyzed. RESULTS: The influence factors of equilibrium solubility include composition of buffers, temperature, time of oscillation, time of sedimentation, techniques for separation of solid and liquid phases etc. CONCLUSION: To ascertain the BCS classification of drugs, the first step is to determine the equilibrium solubility of drugs under physiological pH conditions. To date, there is no accepted standard method for the determination of equilibrium solubility. This paper introduces the basic procedure and technical requirements of equilibrium solubility experiments recommended by WHO, which would provide instructive and practical assists to conduct of equilibrium solubility experiments and standardize its application in BCS classification and biowaiver.
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Objective To prepare and characterize ursolic acid nanoparticles (UANs), and to investigate its improvement of equilibrium solubility and dissolution rate. Methods UANs were prepared by emulsion solvent evaporation method, and followed by freeze-drying. The organic phase was trichloromethane containing 30% ethanol, the aqueous phase is ultrapure water, poloxamer 188 was as surfactant and cryoprotectant. The optimal conditions for preparing nanoparticles were screened out using single-factor experiment. The particle size was used as the basis for optimization experiment. The following six main parameters had significant influences on particle size were picked out, including the concentration of poloxamer 188, volume ratio of organic to water phase, homogenate speed and homogenate time, as well as homogenization pressure and cycles. And then, dynamic light scattering equipment was used to analyze the mean particle size, the morphology of UANs powder obtained was presented by scan electronic micro-scope (SEM). The UANs weather and how changes in surface chemical character and physical structure was estimated by using X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The equilibrium solubility study and dissolution test were carried on raw ursolic acid (UA) and UANs. Results The optimal conditions of preparation UANs: 0.05% of poloxamer 188, 1:4 of volume ratio of organic to water phase, 7 000 r/min of homogenate speed for 2 min and a homogenization pressure of 50.0 MPa for 6 times. Based on the optimal conditions, the mean particle size was (157.5 ± 28.0) nm and Zeta potential of (20.33 ± 1.67) mV. Particle distribution of UANs illustrated that UA had been nanoscale with uniform particle size distribution. SEM showed that UANs were nearly spherical. By the XRD and DSC, we could acquaint UA in UANs had the same chemical structure as the raw UA but had been amorphous state. The result of solubility test figured that the equilibrium solubility of UANs was 13.48 times in SGF, 11.79 times in SIF and 23.99 times in deionized water than raw UA. The dissolution rate of UANs prepared by ESE method has been up to 14.72 times in SGF and 74.35 times in SIF. Conclusion This study indicates that the emulsion solvent evaporation method has an array of valued on improving water solubility of UA, and it will have benefit on enhancing oral bioavailability.
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Objective:To determine the equilibrium solubility and n-octanol/water partition coefficients (Papp)of cinnamon acid and cinnamaldehyde. Methods:The equilibrium solubility of cinnamon acid and cinnamaldehyde in different solutions was determined by HPLC,and their n-octanol/water partition coefficients were determined by a shaking flask method combined with HPLC-DAD. Results:When the pH of solution was 7.8,the equilibrium solubility of cinnamon acid was the largest,while that of cinnamaldehyde was the largest in pH 6.8 solution. The scopes of lgPappof cinnamon acid and cinnamaldehyde in different buffer solutions(pH 1.2-7.8) were -1.04-2.27 and 0.29-1.67, respectively, while those in n-octanol/water solvent were 0.85 and 1.26, respectively. Conclusion:The method is simple,accurate and fast to predicate the absorption of chemical components. In gastrointestinal physiological environment,cinnamaldehyde has good absorption, while cinnamon acid is with poor absorption in stomach and with better absorption in intestinal.
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Objective:To determine the equilibrium solubility and the apparent oil/water partition coefficients of nicotinate-curcu-min ester,so as to provide basis for the new formula design. Methods:Nicotinate-curcumin ester was dissolved in buffer solution with pH of 1.2-7.8. HPLC was used to detect the equilibrium solubility of nicotinate-curcumin ester in various solutions. The apparent oil/water partition coefficients in octanol-water and octanol-buffer solution system were measured by a shaking-flask method. Results:The solubility of nicotinate-curcumin ester in pH 6.8 was the highest. The apparent oil-water partition coefficients of nicotinate-curcumin ester in pH 1.2,5.8,6.5 and 7.8 were lgPapvalues within the range(lgPap=1.69-1.98) beneficial to the absorption in vivo. But in pH 2,5 and 6.8,the lgPapvalues were greater than 2 with strong lipophilicity. Conclusion:The equilibrium solubility as well as ap-parent oil/water partition coefficients of nicotinate-curcumin ester is greatly influenced by the pH value of media. In the pH value with relatively high solubility,lipophilicity is stronger,suggesting it is difficult to be absorbed by the body and needs to be further studied on dosage forms.
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Objective To determine the solubility of rhein in different vehicles and its partition coefficients in the n-octanol-water system for designing new formulations. Methods High performance liquid chromatography(HPLC) method was established to determine the concentration of rhein in water,different pH solutions and different solvents;the partition coefficients for the n-octanol- buffer solution systems were determined by shaking flask method. Results The equilibrium solubility of Rhein was 3.89 μg·mL-1and the lgP was 2.79 in water at 37 ℃.The solubility of rhein was increased with the raise of pH, which could reach 362.20 and 431.65 μg·mL-1in phosphate buffer solution at pH 6.8 and 7.4,respectively.Solubility of rhein in the semi polar solvent was relatively good,which can up to 2 971.74 μg·mL-1in PEG400.The oil-water partition coefficients of rhein were decreased with the increase of pH,and were 0.83 and 0.54 in phosphate buffer solution at pH 6.8 and 7.4,respectively. Conclusion Rhein is almost not soluble in water.With the raise of pH,the solubility is increased but the oil-water partition coefficient is decreased.
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ABSTRACT BCS (Biopharmaceutics Classification System) and BDDCS (Biopharmaceutics Drug Disposition Classification System) were proposed as tools for classifying drugs into four categories. Both systems consider the solubility as an important characteristic for the classification of compounds in drug development and in vivo disposition prediction. Although some results of drug solubility can be found in the literature, the aforementioned characteristic is not entirely clear when considering didanosine (ddI). Based on that, the solubility of ddI was evaluated using equilibrium and intrinsic dissolution methods. For the equilibrium method, excess amount of ddI was added to each media until obtaining a supersaturated solution and the mixture was submitted to agitation at 37 °C. For the intrinsic dissolution method, the drug was compressed into the Wood's apparatus matrix and subjected to dissolution in each media with agitation at 37 °C. The results obtained from the equilibrium method indicated that it was necessary 139.37 mL of pH 1.2 media, 87.72 mL of pH 4.5 media, 12.54 mL of pH 6.8 media, 5.03 mL of pH 7.5 media and 7.65 mL of purified water for drug solubilization. Furthermore, a very fast intrinsic dissolution rate (IDR) was obtained for each media: 0.1 mg/min/cm² (pH 1.2), 0.2 mg/min/cm² (pH 4.5), 0.2 mg/min/cm² (pH 6.8), 0.1 mg/min/cm² (pH 7.5) and 0.1 mg/min/cm² (purified water). Based on these results, ddI can be considered as a highly soluble drug for both equilibrium and intrinsic dissolution methods.
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Solubility , Biopharmaceutics , Didanosine/analysis , Systems Analysis , Pharmaceutical Preparations/classificationABSTRACT
Objective: To prepare the solid dispersion of rutin colloidal silicon dioxide (Ru-CSD-SD) and to promote the rutin oral absorption function, in order to evaluate its in vivo and in vitro oral absorption. Methods: Composition and method of Ru-CSD-SD were investigated by single factor test; Equilibrium solubility experiments, differential thermal analysis (DSC), and X-ray diffraction (XRD) were used to determine the Ru-CSD-SD. Cumulative dissolution rates and pharmacokinetic parameters of Ru-CSD-SD were evaluated by drug releasing in vitro and in vivo. Results: The preparation conditions of Ru-CSD-SD was selected on the basis of single factor test: Colloidal silicon dioxide AEROPERL® 300 pharma (CSD300) was used as carrier, the ratio of drug (rutin) and carrier (CSD300) was 1∶2, and the method was solvent evaporation. After preparation of Ru-CSD-SD, the equilibrium solubility of rutin increased by 2.7 times from 72.69 to 198.73 mg/L; The DSC and XRD were indicated that rutin existed in the solid dispersions at amorphous form. And cumulative dissolution rates of Ru-CSD-SD reached (82.01 ± 1.04)% in 5 min. After oral administration of rutin ordinary tablets and Ru-CSD-SD, t1/2 were 1.078, and 10.899 h, tmax were 1.5, and 0.5 h, and Ru-CSD-SD of Cmax (103.45 μg/mL) was 15.46 times of ordinary tablets (6.69 μg/mL). Ru-CSD-SD of AUC0-∞ (170.406 μg∙h/mL) was 12.20 times of ordinary tablets (13.965 μg∙h/mL). Conclusion: The Ru-CSD-SD with CSD300 can increase the solubility, dissolution rate, and bioavailability.
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Objective To study the equilibrium solubility and oil/water partition coefficient of Hawthorn leaves flavonoids (HLF) components, and compare their similarity, to lay the foundation for the characterization of the overall water soluble and fat soluble HLF components. Methods Taking HLF components as model drug, rutin, quercetin, and hyperin as representative components. The HPLC method was used to determine the equilibrium solubility and apparent oil/water distribution coefficient (Papp) of the components at different pH values and water. The similarity was evaluated by the vector cosine method (cosines) and Grubbs method (Grubbs). Chromatographic conditions: The chromatographic column was Zorbax Eclipse Plus C18 column (250 mm × 4.6 mm, 5 μm), and the flow phase was acetonitrile (A) - 0.4% phosphate solution (B). The gradient elution program was 0—10 min (80% B), 10—11 min (80%—60% B), 11—20 min (60% B), 20—21 min (60%—80% B), and 21—25 min (80% B); The detection wavelength was 360 nm; The volume flow was 0.8 mL/min; The column temperature was 40 ℃. Results The equilibrium solubility and Papp of rutin, quercetin, hyperin were similar in different pH buffer solution and water. The solubility value of lutin, quercetin, and hyperoside in thebuffer solution of different pH were 0.998, 0.988, and 0.987, respectively. The cosine value of the apparent oil-water distribution coefficient was 0.976, 0.981, and 0.978, respectively. The cosine value was greater than 0.9. The Grubbs value of equilibrium solubility of lutin, quercetin and hyperoside were 1.057, 1.083, 1.124, 1.117, 1.022, 1.030, 1.082, and 1.112, respectively. The Grubbs values of the apparent oil-water distribution coefficient were 1.125, 1.107, 1.079, 1.034, 1.041, 1.037, 1.129, and 1.128. The results of Grubbs were less than G critical value of 1.153, and the similarity was good. Conclusion The similarity analysis reflects that the degree of dispersion of components objectively, which could increase the science of components evaluation and provide the basis for the formulation design of components of traditional Chinese medicine.
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Objective:To determine the equilibrium solubility and the apparent oil/water partition coefficient of nebivolol hydrochloride to provide experimental basis for the development of new preparations.Methods:The concentration of nebivolol hydrochloride was determined by an HPLC method,and a saturated solution method and a shake-flask method were respectively applied to determine the equilibrium solubility and the apparent oil/water partition coefficient of nebivolol hydrochloride in water,0.1 mol·L-1 HCl solution and phosphate buffer solution with different pH values(pH2.0,pH6.8,pH7.4 and pH8.0).Results:At (37±0.5)℃,the equilibrium solubility of nebivolol hydrochloride in water and in 0.1 mol·L-1 HCl solution was 722.53 μg·ml-1and 56.07μg·ml-1,respectively.The apparent oil/water partition coefficient (Log P) of nebivolol hydrochloride was 1.17 and 1.32,respectively.Within the pH range of 2.0-7.4,with the increase of pH value, the equilibrium solubility and the Log P decreased and increased,respectively,while pH value increased from 7.4 to 8.0,the equilibrium solubility of nebivolol hydrochloride increased and Log P decreased.Conclusion:The method is accurate and reliable.Nebivolol hydrochloride has poor water solubility,and the equilibrium solubility and the Log P are both influenced by pH values.
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Objective To determine equilibrium solubility and apparent partition coefficient of salicylic acid at 25 ℃,and to provide a theoretical basis for design and preparation of its formulation.Methods Equilibrium solubility and apparent partition coefficient (Papp) of salicylic acid were respectively investigated in water,hydrochloric acid solution (pH 1.0) and phosphate buffer solution system (pH 2.0,3.0,4.0,5.0,6.0,7.0,7.8) at 25 ℃.The shake flask method and HPLC were used.The column was Waters C18 (4.6 mm ×250 mm,5 μn) with the mobile phase as methanol-0.1％ phosphoric acid water (47:53).The column temperature was room temperature.The flow rate was 1.0 mL·min-1.The detection wavelength was 270 nm and injection volume was 20 μL.Results Equilibrium solubility of salicylic acid was (2.205 ±0.020) mg·mL-1 at 25 ℃ in Water and its Papp was (6.18 ±0.08).The solubility were (1.169 × 10-3 ±7.40 × 10-6),(2.250 ±0.010),(2.410±0.010),(2.694 ±0.003),(5.208 ±0.010),(5.826 ±0.006),(6.255 ±0.030),(3.353 ±0.070) mg·mL-1,respectively,at hydrochloric acid solution (pH 1.0) and phosphate buffer solution system (pH 2.0,3.0,4.0,5.0,6.0,7.0,7.8),and the corresponding Papp were (16.39 ±0.19),(4.23 ±0.07),(6.03 ±0.11),(5.56 ±0.10),(1.25 ±0.01),(0.27 ± 0.001),(0.08 ± 0.001) and (0.07 ± 0.002),respectively.Conclusion The solubility of salicylic acid increases and its oil-water partition coefficient declines with pH value increasing.Salicylic acid is slightly soluble in water and oil.It belongs to Class Ⅳ drug in Biopharmaceutics Classification System (BCS).
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Objective To determine equilibrium solubility and apparent oil/water partition coefficient of ephedra alkaloid in the compatibility Ephedrae Herba-Aconiti Lateralis Radix Praeparata; To provide a basis for transdermal delivery.Methods The extract was prepared by 70% ethyl alcohol and D101 macroporous absorbent resins. Dissolvability of its main effective components (ephedrine and pseudoephedrine) in the compatibility Ephedrae Herba-Aconiti Lateralis Radix Praeparata was determined by precipitation method and HPLC method; the oil/water partition coefficient of ephedrine and pseudoephedrine in n-octanol-water buffer solution system were determined by shaking flask method.Results The extract had optimum solubility in methyl alcohol and acetonitrile, and ephedrine and pseudoephedrine had optimum solubility in buffered solution of pH 7.4. Oil/water partition coefficient of ephedrine and pseudoephedrine in n-octanol-water system was 0.101 with lgP=-0.99 and 0.076 with lgP=-1.12. Oil-water partition coefficients of ephedrine and pseudoephedrine in the extract were affected by pH.Conclusion The extract has optimum solubility in high polar solvents. Ephedrine and pseudoephedrine have certain fatsoluble and water-soluble in suitable pH, which was beneficial for transdermal absorption.
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Objective: Taking luteolin-7-O-β-D-glucuronide, rosmarinic acid, and tilianin as indexes, the concentration of extracts from Dracocephalum moldavica (EDM) and their index components in various media, surfactant solution, and apparent oil/water partition coefficient (P) was detected in different pH values, then the stability of EDM in artificial gastrointestinal fluid was investigated. This research would give the reference for the selection and preparation of further novel formulation. Methods: Apparent solubility of EDM in various media and surfactant solution was determined by precipitation method and a shake flask method was used to determine the P of octanol-water/phosphate buffer salt, the stability of EDM in artificial gastrointestinal fluid was investigated. HPLC was adopted to determine the concentration of the index components with Shim-pack ODS column (250 mm×4.6 mm, 5 μm), mobile phase of acetonitrile (A)-0.5% formic acid aqueous solution (B) for gradient elution (0-30 min, 15% A; 30-55 min, 15%→25% A; 55-80 min, 25%→35% A) as the mobile phase at a flow rate of 1.0 mL/min. The detection wavelength was set at 324 nm and the column temperature was maintained at 35℃. Results: At 37℃, the equilibrium solubility of the three index components in acid buffer solution increased obviously in water, but in alkaline the buffer solution of the equilibrium solubility decreased with pH increasing. In 32 g/L sodium dodecyl sulfate solution, the equilibrium solubility of luteolin, rosmarinic acid, and tilianin increased to 1679.61, 1249.2, and 2765.27 μg/mL. The P of luteolin-7-O-β-D-glucuronide, rosmarinic acid, and tilianin were 0.1731 (lgP=-0.7618), 0.068 4 (lgP=-1.1650), and 1.0829 (lgP=0.0346), and increased as pH rising. EDM in artificial gastrointestinal fluid was stable (except luteolin). Conclusion: The methods can be used to determine the apparent solubility, the P value of the extracts and their index components; The EDM in artificial gastrointestinal fluid is stable. The research would give the reference for the selection and preparation of the further novel formulation.
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Objective: Optimization of ginkgolides components (GC) self-microemulsifying drug delivery system (SMDDS) (GC-SMDDS) and similarity analysis on each drug release. Methods: Using equilibrium solubility to screen the oil phase, emulsifier, and co-emulsifier; Taking appearance, the proportion of microemulsion particle size, Zeta potential, surfactants and co-surfactants, and surfactant mixing ratio of the oil phase as study factors, pseudo-ternary phase diagrams were used to screen GC-SMDDS process. SMEDDS of drug loading, particle size distribution, Zeta potential, and stability were evaluated. With the aid of the similarity factor and the curve linear regression slope analysis, the similarity between the composition of the component and the rate and extent of drug release was analyzed. Results: Optimal prescription of polyoxyethylene and polyethylene glycol 200 mass ratio of 4:1, ethoxylates and polyethylene glycol quality and bitterness total mass of 200 capric triglycerides ratio of 9:1, drug content of 100 mg/g. Particle size under 40 nm, ginkgolides 48 h internal components from microemulsion to room temperature, high temperature, and low temperature stability is good. The release quantity achieves the synchronous drug release with the similarity of 96.9%. Conclusion: The SMDDS not only can improve the dissolution of difficult soluble drugs, but also independently regulate the drug release behavior of each component so as to make the drug release maintain good consistency.
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OBJECTIVE:To determine the solubility and apparent oil and water partition coefficient (lg P) of saponin H1,and provide reference for dosage form design and druggability research of saponin. METHODS:HPLC-ELSD was conducted to deter-mine the equilibrium solubility of saponin H1 in different organic solvents and pH buffer solutions;shaking flask was applied to de-termine lg P value of saponin H1. RESULTS:The equilibrium solubility of saponin H1 in water,methanol and ethanol at 25 ℃ was 0.09175 g/L,96.51 g/L and 46.89 g/L,respectively. The solubility increased apparently at high pH within pH range at 7.6-10.0;the lg P value was between 0.695-0.773 in buffers within pH range at 6.0-8.0. CONCLUSIONS:Saponin H1 and the oleanolic acid type saponins belong to low solubility, low transmission components, so it is not suitable for use as a conventional oral formulation is developed.
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Objective To study the physical and chemical properties of silibinin; To lay foundation for optimal formulation design.Methods The high performance liquid chromatography method was used to detect the equilibrium solubility of silibininin in various solutions. The partition coefficients of silibinnin in the n-octalution-water and n-octalution-buffer solution systems were determined by shaking flask method. The destructive tests were carried out on silibinin.Results The equilibrium solubility of silibininin at 25℃ was 1.352 mg/L in water and the largest in acetonitrile, and increased in basic buffer solutions and after adding surfactants, of which sodium dodecyl benzene sulfonate was the strongest in solubilizing ability. The apparent oil-water partition coefficient of silibinnin was 61.39. Silibinnin was unstable in the acidic, basic, oxidizing and reducing solutions.Conclusion The experiment results can provide references for designing new preparations of silibinin.
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Objective To establish a reversed-phase high performance liquid chromatograph ( RP-HPLC ) method for determination of equilibrium solubility and oil/water partition coeficient of phloridzin in different solvents. Methods A RP-HPLC method was established to detect the concentration of phloridzin in water and different organic solvents. The partition coefficients in the n-octanol-water/buffer solution systems of phloridzin were determined by shaking flask method. The Inertsil ODS-3 (4.6 mm×150 mm, 5μm) column was used and the detection wavelength was 284 nm.The flow rate was 1.0 mL??min-1, and acetonitrile-0.05% phosphoric acid(30??70)was used as mobile phase. Results The equilibrium solubility of phloridzin was 2.07 mg??mL-1 in water and 838.63 mg??mL-1 in methanol at 25 ℃.A good linear relationship of phloridzin was obtained within the range of 0.054 9-1.098 0 μg.The regression equation was Y=2 152.9X+7.26 (r=0.999 9).The solubility values of phloridzin were higher in ethanol and propylene glycol than in other solvents. Conclusion RP-HPLC method is simple, quick and accurate for the determination of phloridzin.Phloridzin was almost insoluble in petroleum ether and poorly soluble in water.The equilibrium solubility is higher in methanol than in other solvents. The apparent distribution coefficient of phloridzin varies significantly with pH under the alkaline conditions but less in the acidic solution.
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OBJECTIVE:To determine the equilibrium solubility of albendazole(ABZ)and its apparent oil-water partition coef-ficient. METHODS:The equilibrium solubility of ABZ in various solutions was determined at 37 ℃ by HPLC and saturation solu-bility method,including water,7 kinds of common organic solvents with different polarities(methanol,ethanol,etc.),organic ac-id(oleic acid,glacial acetic acid,lactic acid,formic acid),hydrochloric acid of pH 1.2,phosphate buffer solution(PBS)of dif-ferent pHs(2.0-7.8)and 6 kinds of common surfactants with mass concentrations of 10,50 and 100 mg/ml(polysorbate 80,polox-amer,etc.). The apparent oil-water partition coefficient(P)was calculated with the concentration ratio of ABZ in oil phase(N-oc-tyl alcohol)and water phase(water and PBS of different pHs)after partition equilibrium. RESULTS:The equilibrium solubility of ABZ reached(0.26±0.02)μg/ml in water,with the lgP of 3.66±0.01. The equilibrium solubility of ABZ in common organic sol-vents and organic acids was higher than in water. The higher the polarity of the organic solvent was and the weaker of organic acid was,the weaker of its ability to solubilize ABZ would be. The equilibrium solubility of ABZ was higher in the medium of pH 1.2-2.5 than in that of pH 5.0-7.8. The ability of the surfactant to solubilize ABZ was related to its type,and the higher of the mass concentration of the surfactant was,the stronger of its ability to solubilize ABZ became. lgP was less than 1.6 at pH 1.2-2.0 and changed little at pH 5.0-7.8 [(3.71 ± 0.26)-(3.68 ± 0.26)]. CONCLUSIONS:ABZ is insoluble in water. Its equilibrium solubility demonstrates a negative correlation with the polarity of the organic solvent and a positive correlation with the acidity of the organic acid and with the mass concentration of the surfactant. It has higher water solubility and lower lipid solubility in a strong acidic en-vironment,and higher lipid solubility and weaker water solubility in weak acidic,weak basic and neutral environments.
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Objective To study the effect of surfactants on the dissolution profiles of poorly water-soluble acidic drug nimesulide from sustained-release tablets.Methods The anionic surfactant sodium dodecyl sulfate (SDS), cationic sur-factant cetyltrimethyl ammonium bromide (CTAB) and nonionic surfactant polysorbate 80 (Tween 80) were used to prepare nimesulide micelles .The effect of the buffer , surfactant and ionic strength on the equilibrium solubility of the drug and the in vitro release of sustained-release tablets was studied .Results and Conclusion In pH 1.2 HCl solution, water and pH 6.8 phosphate buffer, the solubilization capacity of CTAB was the highest.However, in pH 9.0 Tris buffer, when CTAB concen-tration was at about 1%, the equilibrium solubility of nimesulide was at the trough value .The in vitro release results were similar to those of equilibrium solubility and the kinetic pattern conformed to the first order equation according to the coefficient R .