Construction of a physiologically based pharmacokinetic model of paclobutrazol and exposure estimation in the human body.

Paclobutrazol (PBZ) is a plant growth regulator that can delay plant growth and improve plant resistance and yield. Although it has been widely used in the growth of medicinal plants, human beings may take it by taking traditional Chinese medicine. There are no published studies on PBZ exposure in humans or standardized limits for PBZ in medicinal plants. We measured the solubility, oil-water partition coefficient (logP), and pharmacokinetics of PBZ in rats and established a physiologically based pharmacokinetic (PBPK) model of PBZ in rats. This was followed by extrapolation to healthy Chinese adult males as a theoretical foundation for future risk assessment of PBZ. The results showed that PBZ had low solubility and high fat solubility. Pharmacokinetic experiments showed that PBZ was absorbed rapidly but eliminated slowly in rats. On this basis, the rat PBPK model was successfully constructed and extrapolated to healthy Chinese adult males to predict the plasma concentration-time curve and exposure of PBZ in humans. The construction of the PBPK model of PBZ in this study facilitates the determination of the standard formulation limits and risk assessment of PBZ residues in medicinal plants.

Oil-water partition coefficient preparation and detection in the dihydroartemisinin self-emulsifying drug delivery system.

BACKGROUND: The aim of the present study is to increase the solubility of dihydroartemisinin (DHA) using the self-emulsifying drug delivery system (SEDDS). METHODS: We first conducted solubility test and ternary phase diagram, then, in order to optimize the formulation of the DHA self-emulsifying agent, the design mixture method was selected in the design expert software. Next, optimal prescription validation and preliminary formulation evaluation were conducted. By comparing the oil-water partition coefficient in vitro, the improvement of the in vivo osmotic absorption of DHA via self-emulsification was evaluated. RESULTS: The optimal prescription ratio of oleic acid polyethylene glycol glyceride, polyoxyethylene hydrogenated castor oil, and diethylene glycol monoethyl ether in the DHA self-emulsifying preparation = 0.511:0.2:0.289 (w/w/w), with a drug-loading capacity of 26.3634 mg/g, solubility of 2.5448 mg/ml, and self-emulsification time of 230 s. The solubility self-emulsification was approximately 20.52 × higher in DHA than in the crude drug. The self-emulsification could improve DHA permeability and promoting in vivo DHA absorption. CONCLUSION: The DHA SEDDS could significantly improve DHA solubility and in vivo absorption.

Accurate Physical Property Predictions via Deep Learning.

Neural networks and deep learning have been successfully applied to tackle problems in drug discovery with increasing accuracy over time. There are still many challenges and opportunities to improve molecular property predictions with satisfactory accuracy even further. Here, we proposed a deep-learning architecture model, namely Bidirectional long short-term memory with Channel and Spatial Attention network (BCSA), of which the training process is fully data-driven and end to end. It is based on data augmentation and SMILES tokenization technology without relying on auxiliary knowledge, such as complex spatial structure. In addition, our model takes the advantages of the long- and short-term memory network (LSTM) in sequence processing. The embedded channel and spatial attention modules in turn specifically identify the prime factors in the SMILES sequence for predicting properties. The model was further improved by Bayesian optimization. In this work, we demonstrate that the trained BSCA model is capable of predicting aqueous solubility. Furthermore, our proposed method shows noticeable superiorities and competitiveness in predicting oil-water partition coefficient, when compared with state-of-the-art graphs models, including graph convoluted network (GCN), message-passing neural network (MPNN), and AttentiveFP.

Biopharmaceutics classification evaluation for paris saponin VII.

To study the biopharmaceutics characteristics of paris saponin VII (PSVII). The solubility of PSVII was evaluated by measurement of the equilibrium solubility in different solvents and media. The permeability of PSVII was evaluated by measuring the oil/water partition coefficient (lgPapp) and determining the apparent permeability coefficient (PCapp) on a mono-layer Caco-2 cell model. The effects of p-glycoprotein and multidrug resistance related protein 2 on PSVII transport in mono-layer Caco-2 cell model were further investigated. Finally, the small intestinal absorption of PSVII was investigated in rat. In solvents of different pH, the equilibrium solubility of PSVII was quite low, and the dose number of PSVII was larger than 1. The lgPapp of PSVII was less than 0. The apparent permeability coefficient [PCapp(AP-BL)] of PSVII in mono-layer Caco-2 cell model was less than 14.96 × 10-6 cm·s-1, and the efflux ratio of PSVII in mono-layer Caco-2 cell model was less than 1. The transport rate of PSVII in mono-layer Caco-2 cell model was not affected by the inhibitors of p-glycoprotein and multidrug resistance related protein 2. After oral administration, PSVII could be detected in rat intestinal contents, but could not be detected in the small intestinal mucosa. PSVII showed low solubility and permeability, which would result in low oral bioavailability in clinic. PSVII belonged to Class IV compound in biopharmaceutics classification system.

[Characterization of oil/water partition coefficient of chishao terpene glucoside components based on contribution rate of representative components for myocardial ischemia].

The components of traditional Chinese medicine(TCMCs) are the basic unit of raw materials for Chinese medicines, and their physical and chemical properties directly affect the choice of dosage forms and the optimization of prescriptions. However, most of TCMCs are multi-component complex systems, and the characterization of their overall properties is still in the exploration stage. On the basis of biological activity, the representative components are determined, and then the individual characteristics are fitted with the weight coefficient of efficacy contribution rate, which may provide reference for characterizing the overall properties of TCMCs. In this study, with the pharmacological effects of isoproterenol(ISO)-induced myocardial ischemia in rats as the indicators, the pharmacodynamic contribution rates of three representative components of chishao terpene glucoside components(CSTGCs) were evaluated by the normalization weighting method. The contribution rates of paeoniflorin, paeoniflorin and benzoylpaeoniflorin were 54.87%, 32.46% and 12.67%, respectively. The oil-water partition coefficients of paeoniflorin, albiflorin, benzoylpaeoniflorin in water and buffer solutions with different pH values were measured, and the oil-water partition coefficients of CSTGCs were characterized by the weight of their pharmacodynamics contribution rate. The results showed that the apparent oil-water partition coefficient(log P) of CSTGCs in the phosphate buffer system such as n-octanol-water(pH 2.0, 2.5, 5.0, 5.8, 6.8) were 0.18-0.22, indicating that CSTGCs have common absorption and low permeability, providing basis for the preparation of CSTGCs.

Study on oil-water distribution of taxifolin and its absorption and transport mechanism in Caco-2 cell model / 中草药

Objective: To prepare the taxifolin and determine its apparent oil-water partition coefficient in different media, and to study the mechanism of absorption and transport of taxifolin in Caco-2 cell model. Methods: Taxifolin was prepared by enzymolysis. HPLC was used to determine the saturated solubility of taxifolin in 37 ℃, different pH buffer solution and water, apparent oil-water distribution coefficient of taxifolin obtained by calculation formula of oil-water distribution coefficient; CCK-8 experiment was used to investigate the safe concentration range of taxifolin in Caco-2 cells, and then the single-layer model of Caco-2 cells was used to study the mechanism of bilateral transmembrane absorption and transport. CCK-8 experiment was used to investigate the safe concentration range of taxifolin in HDMEC cells. The inflammatory model of HDMEC cells induced by lipopolysaccharide was established, and the activity of lactic dehydrogenase was detected by the intervention of floxacin. The activity of lactic dehydrogenase was detected by lactic dehydrogenase kit. Results: The lgP values of taxifolin in the following solvents were 0.29 (0.1 mol/L hydrochloric acid), 0.48 (pH 2.0), 0.46 (pH 5.8), 0.34 (pH 6.8), 0.26 (pH 7.4), and 0.38 (water), respectively; There was no significant toxic effect on Caco-2 cells in the range of 50-500 μg/mL; There was no significant difference in Papp value of bilateral transport between different concentrations of taxifolin in Caco-2 monolayer cell model, and it was less than 1 × 10-6 cm/s and ER was less than 2. There was no significant toxic effect on HDMEC cells in the range of 50-300 μg/mL; After treatment with taxifolin, compared with LPS stimulation group, the activity of LDH in each treatment group was decreased significantly (P < 0.05), and the activity of LDH was decreased significantly in the range of 50-100 μg/mL, and tended to be stable in the range of 100-250 μg/mL. Conclusion: Taxifolin is a kind of drug which is difficult to absorb in the intestine. The mechanism of transmembrane transport is passive transport. It can inhibit the inflammation of hdmec cells induced by LPS and has anti-inflammatory activity.

Characterization of oil/water partition coefficient of chishao terpene glucoside components based on contribution rate of representative components for myocardial ischemia / 中国中药杂志

The components of traditional Chinese medicine(TCMCs) are the basic unit of raw materials for Chinese medicines, and their physical and chemical properties directly affect the choice of dosage forms and the optimization of prescriptions. However, most of TCMCs are multi-component complex systems, and the characterization of their overall properties is still in the exploration stage. On the basis of biological activity, the representative components are determined, and then the individual characteristics are fitted with the weight coefficient of efficacy contribution rate, which may provide reference for characterizing the overall properties of TCMCs. In this study, with the pharmacological effects of isoproterenol(ISO)-induced myocardial ischemia in rats as the indicators, the pharmacodynamic contribution rates of three representative components of chishao terpene glucoside components(CSTGCs) were evaluated by the normalization weighting method. The contribution rates of paeoniflorin, paeoniflorin and benzoylpaeoniflorin were 54.87%, 32.46% and 12.67%, respectively. The oil-water partition coefficients of paeoniflorin, albiflorin, benzoylpaeoniflorin in water and buffer solutions with different pH values were measured, and the oil-water partition coefficients of CSTGCs were characterized by the weight of their pharmacodynamics contribution rate. The results showed that the apparent oil-water partition coefficient(log P) of CSTGCs in the phosphate buffer system such as n-octanol-water(pH 2.0, 2.5, 5.0, 5.8, 6.8) were 0.18-0.22, indicating that CSTGCs have common absorption and low permeability, providing basis for the preparation of CSTGCs.

Biopharmaceutics classification evaluation for paris saponin VII / 中国天然药物

To study the biopharmaceutics characteristics of paris saponin VII (PSVII). The solubility of PSVII was evaluated by measurement of the equilibrium solubility in different solvents and media. The permeability of PSVII was evaluated by measuring the oil/water partition coefficient (lgP) and determining the apparent permeability coefficient (PC) on a mono-layer Caco-2 cell model. The effects of p-glycoprotein and multidrug resistance related protein 2 on PSVII transport in mono-layer Caco-2 cell model were further investigated. Finally, the small intestinal absorption of PSVII was investigated in rat. In solvents of different pH, the equilibrium solubility of PSVII was quite low, and the dose number of PSVII was larger than 1. The lgP of PSVII was less than 0. The apparent permeability coefficient [PC] of PSVII in mono-layer Caco-2 cell model was less than 14.96 × 10 cm·s, and the efflux ratio of PSVII in mono-layer Caco-2 cell model was less than 1. The transport rate of PSVII in mono-layer Caco-2 cell model was not affected by the inhibitors of p-glycoprotein and multidrug resistance related protein 2. After oral administration, PSVII could be detected in rat intestinal contents, but could not be detected in the small intestinal mucosa. PSVII showed low solubility and permeability, which would result in low oral bioavailability in clinic. PSVII belonged to Class IV compound in biopharmaceutics classification system.

Investigation of Physicochemical Properties and Determination Methods of Liposomal Entrapment Efficiency of Dichroa Alkali Hydrochloride / 中国实验方剂学杂志

Objective: To study on the physical and chemical properties of dichroa alkali hydrochloride and to establish a method for the determination of entrapment efficiency of dichroa alkali hydrochloride liposomes. Method: HPLC was used to determine the content of dichroa alkali hydrochloride with mobile phase of acetonitrile-water-triethylamine-glacial acetic acid(9:91:0.35:0.75) and detection wavelength at 265 nm.The oil-water partition coefficient of this compound in different pH range was measured by shake flask method.The stability of the dichroa alkali hydrochloride in phosphate buffer solution with different pH after sterilization at 125℃ for 30 min was investigated.Ammonium sulfate gradient method was used to prepare dichroa alkali hydrochloride liposomes.The microcolumn was prepared by dextran gel and cation exchange resin,respectively.Then the free drug and liposome were separated by centrifugation,the drug content was measured,and the encapsulation efficiency was calculated.The t-test was performed using SPSS 20.0 software,the differences between these two methods were compared. Result: In the pH 6-9,the oil-water partition coefficient of dichroa alkali hydrochloride increased with increasing of pH,which was between 0.016 and 1.44;the recovery rate of dichroa alkali hydrochloride after sterilization was 37.16%-57.91%.Between the dextran gel microcolumn centrifugation and the cation exchange resin microcolumn centrifugation,there was no significant difference in the entrapment efficiency of the liposomes. Conclusion: Dichroa alkali hydrochloride is suitable for preparation of liposomes.However,its stability is not ideal,so the experimental temperature should be strictly controlled in the preparation process.Dextran gel microcolumn centrifugation and cation exchange resin microcolumn centrifugation can be used to determine the entrapment efficiency of dichroa alkali hydrochloride liposomes,and the cation exchange resin microcolumn centrifugation is suggested after comparison.

[Biopharmaceuticals classification system(BCS) of nuciferin in Nelumbinis Folium].

Nuciferin is the main active ingredients in Nelumbinis Folium， which was proved to have good hypolipidemic， antioxidative and anti-inflammatory bioactivities. Currently， in vivo pharmacokinetic studies of nuciferin showed different results based on different animal models. In vitro evaluation experiments were low-cost， stable and controllable. Biopharmaceutical classification system(BCS) was an effective and reliable in vitro simulation method to evaluate the bioavailability of oral drugs. It was a scientific framework for classifying drugs or active pharmaceutical ingredients(API) according to their solubility and impermeability in vitro. In the study， BCS was applied in an active ingredient in traditional Chinese medicine(TCM)， which was consisted of numerous chemical components. To study the equilibrium solubility of nuciferine， ideal solution model， Ape blat model and polynomial model were adopted. The permeability was measured based on partition coefficient(logP) and distribution coefficient(logD). Besides， in vitro apparent permeabilities of Caco-2 cells and murine intestine tissues were evaluated. Nuciferine was classified as BCSⅠ， since it had a good solubility and permeability in all methods under acidic conditions. However， in neutral and alkaline environments， nuciferine was classified as BCSⅣ by using everted intestinal sac. It indicated that the species of experimental animals has a significant influence on the absorption of nuciferine. This experiment can provide data support to the prediction in a complex environment(medicinal materials and absorbed parts). The application of BCS on TCM ingredients provided a new in vitro method to evaluate and screen out the druggability of TCM ingredients.

Determination of Equilibrium Solubility and Apparent Oil-water Partition Coefficients of Nicotinate-curcu-min Ester / 中国药师

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.

Preformulation study on antirheumatic drug DK-507 / 国际药学研究杂志

Objective To perform a preformulation study for a new antirheumatic drug DK-507 so as to provide theoretical basis for its preparation research.Methods The appearance,crystal form and solubility of DK-507 were investigated.A high perfor-mance liquid chromatography(HPLC)method for the quantitative determination of DK-507 was established.The apparent oil/water (O/W)partition coefficient of DK-507 and the equilibrium solubility of the drug under different pH conditions were determined. Re-sults DK-507 is a white crystalline powder,which is odorless,tasteless and insoluble in water.The quantitative HPLC method for the DK-507 determination showed a good linearity in the range of 10-80 μg/ml(R=0.9998).The apparent O/W partition coefficient of DK-507 was determined to be 1.80.In the different pH solutions,the solubility of DK-507 showed a W-form change,with poor solubili-ties in lower pH solutions,which showed a gradient improvement with the increase of the solution pH values.Conclusion The quanti-tative HPLC method for the DK-507 determination,established in this study,is accurate and reliable.The present results indicate that DK-507 is a water-insoluble drug,and according to the O/W partition coefficient,DK-507 seems likely to be prepared into oral solid preparations.

Biopharmaceuticals classification system(BCS) of nuciferin in Nelumbinis Folium / 中国中药杂志

Nuciferin is the main active ingredients in Nelumbinis Folium， which was proved to have good hypolipidemic， antioxidative and anti-inflammatory bioactivities. Currently， pharmacokinetic studies of nuciferin showed different results based on different animal models. evaluation experiments were low-cost， stable and controllable. Biopharmaceutical classification system(BCS) was an effective and reliable simulation method to evaluate the bioavailability of oral drugs. It was a scientific framework for classifying drugs or active pharmaceutical ingredients(API) according to their solubility and impermeability . In the study， BCS was applied in an active ingredient in traditional Chinese medicine(TCM)， which was consisted of numerous chemical components. To study the equilibrium solubility of nuciferine， ideal solution model， Ape blat model and polynomial model were adopted. The permeability was measured based on partition coefficient(logP) and distribution coefficient(logD). Besides， apparent permeabilities of Caco-2 cells and murine intestine tissues were evaluated. Nuciferine was classified as BCSⅠ， since it had a good solubility and permeability in all methods under acidic conditions. However， in neutral and alkaline environments， nuciferine was classified as BCSⅣ by using everted intestinal sac. It indicated that the species of experimental animals has a significant influence on the absorption of nuciferine. This experiment can provide data support to the prediction in a complex environment(medicinal materials and absorbed parts). The application of BCS on TCM ingredients provided a new method to evaluate and screen out the druggability of TCM ingredients.

Preformulation study on novel antiviral drug GZ914 / 军事医学

Objective To study the physical-chemical parameters of antiviral drug GZ 914 and provide data for the preparation design .Methods The appearance , crystal structure and solubility of GZ 914 were investigated .An HPLC method was established to determine the content of GZ 914 in vitro before oil/water partition coefficient and solubility in different pH experiments were calculated .Results GZ914 was a straw yellow powder with a crystalline structure , low water-solubility and good lipotropy .The HPLC method had a good linear relationship within the range of 12-60 μg/ml (r=0.9998).The oil/water partition coefficient of GZ914 was 1.9.Conclusion This analytical method is accurate and reliable.The oil/water partition coefficient indicates that the drug could be formulated as an oral solid preparation.

Determination of Equilibrium Solubility and Apparent Oil/Water Partition Coefficient of Nebivolol Hydrochloride / 中国药师

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.

Investigation of Dissolvability of Ephedra Alkaloid in Compatibility Ephedrae Herba- Aconiti Lateralis Radix Praeparata / 中国中医药信息杂志

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.

The effect of oil-water partition coefficient on the distribution and cellular uptake of liposome-encapsulated gold nanoparticles.

The shape, size, and surface features of nanoparticles greatly influence the structure and properties of resulting hybrid nanosystems. In this work, gold nanoparticles (GNPs) were modified via S-Au covalent bonding by glycol monomethyl ether thioctate with poly(ethylene glycol) methyl ether of different molecular weights (i.e., 350, 550, and 750Da). These modified GNPs (i.e., GNP350, GNP550, and GNP750) showed different oil-water partition coefficients (Kp), as detected using inductively coupled plasma-atomic emission spectroscopy. The different Kp values of the gold conjugates (i.e., 13.98, 2.11, and 0.036 for GNP350, GNP550, and GNP750, respectively) resulted in different conjugate localization within liposomes, as observed by transmission electron microscopy. In addition, the cellular uptake of hybrid liposomes co-encapsulating gold conjugates and Nile red was evaluated using intracellular fluorescence intensity. The results indicated that precise GNP localization in the hydrophilic or hydrophobic liposome cavity could be achieved by regulating the GNP oil-water partition coefficient via surface modification; such localization could further affect the properties and functions of hybrid liposomes, including their cellular uptake profiles. This study furthers the understanding not only of the interaction between liposomes and inorganic nanoparticles but also of adjusting liposome-gold hybrid nanostructure properties via the surface chemistry of gold materials.

Study on Silibinin Preformulation / 中国中医药信息杂志

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.

Preformulation study of curcumenol / 国际药学研究杂志

Objective To study the physical-chemical parameters of curcumenol so as to design its optimal preparations. Methods An HPLC method was established to determine the content of curcumenol. Based on the method,the equilibrium solubility, oil/water partition coefficient and stability of curcumenol were investigated. Results The equilibrium solubility in the pure water was 1.93 mg/ml(25℃)and 2.6 mg/ml(37℃),respectively. The oil/water partition coefficient was in the range of 2.2-3.0. Curcumenol solution was unstable at high temperature under light conditions,while pH value showed little effect. Conclusion The analytical method is accurate and reliable. The solubility of curcumenol can be described as strong lipotropic and slightly soluble in water. Nano-formulation and solubilization technologies could improve its bioavailability significantly. Curcumenol should be stored and operated in a dark and cool place.

Preformulation study of curcumenol / 国际药学研究杂志

Objective To study the physical- chemical parameters of curcumenol so as to design its optimal preparations. Methods An HPLC method was established to determine the content of curcumenol. Based on the method, the equilibrium solubility, oil/water partition coefficient and stability of curcumenol were investigated. Results The equilibrium solubility in the pure water was 1.93 mg/ml (25 °C) and 2.6 mg/ml (37°), respectively. The oil/water partition coefficient was in the range of 2.2-3.0. Curcumenol solution was unstable at high temperature under light conditions, while pH value showed little effect. Conclusion The analytical method is accurate and reliable. The solubility of curcumenol can be described as strong lipotropic and slightly soluble in water. Nanoformulation and solubilization technologies could improve its bioavailability significantly. Curcumenol should be stored and operated in a dark and cool place.