Effect of low-molecular casein and gelatin on absorption of ibuprofen after oral and rectal administration.

Kneaded mixture of ibuprofen with low-molecular gelatin or casein (LM gelatin or LM casein) was prepared, and their in vitro dissolution, release from suppository base and in vivo absorption behaviours were examined. The dissolution rate of ibuprofen from the kneaded mixtures was markedly higher than that of the drug itself. The LM gelatin and LM casein also enhanced the release rate of ibuprofen from suppository base. After oral administration of the kneaded mixture with LM gelatin to beagle dogs, the initial serum concentration was higher than that of the drug alone. On the other hand, LM casein accelerated the absorption of ibuprofen from rectum. However, LM gelatin and LM casein did not affect the bioinversion of R(-)- to S(+)-ibuprofen.     

Investigation of the effect of solubility increase at the main absorption site on bioavailability of BCS class II drug (risperidone) using liquisolid technique

BCS class II drugs usually suffer inadequate bioavailability as dissolution step is the absorption rate limiting step. In this work, the effect of solubility increase at the main absorption site for these drugs was investigated using risperidone as a drug model. Liquisolid technique was applied to prepare risperidone per-oral tablets of high dissolution rate at intestinal pH (6.8) using versatile nonionic surfactants of high solubilizing ability [Transcutol HP, Labrasol and Labrasol/Labrafil (1:1) mixture] as liquid vehicles at different drug concentrations (10–30%) and fixed (R). The prepared liquisolid tablets were fully evaluated and the dissolution rate at pH 6.8 was investigated. The formulae that showed significantly different release rate were selected and subjected to mathematical modeling using DE₂₅, MDT and similarity factor (f2). Depending on mathematical modeling results, formula of higher dissolution rate was subjected to solid state characterization using differential scanning calorimetric (DSC), infrared spectroscopy (IR) and X-ray diffraction (XRD). Finally, the drug bioavailability was studied in comparison to conventional tablets in rabbits. Results showed that liquisolid tablet prepared using Labrasol/Labrafil (1:1) mixture as liquid vehicle containing 10% risperidone is a compatible formula with law drug crystallinity and higher dissolution rate (100% in 25?min). The drug bioavailability was significantly increased in comparison to the conventional tablets (1441.711?μg h/mL and 137.518?μg/mL in comparison to 321.011?μg h/mL and 38.673?μg/mL for AUC and Cp_max, respectively). This led to the conclusion that liquisolid technique was efficiently improved drug solubility and solubility increase of BCS class II drugs at their main absorption site significantly increases their bioavailability.     

不同载体对缬沙坦纳米骨架载药系统溶出行为和生物利用度影响的研究

目的 通过调节纳米骨架载药系统（NDDS）中载体类型和比例实现对缬沙坦体外溶出和体内生物利用度的调控。方法 以缬沙坦作为模型药物,分别选取酸性敏感材料Eudragit E100（E100）、碱性敏感材料Eudragit L100-55（L100-55）作为载体材料,介孔二氧化硅Sylysia 350（S350）、Aerosil 200（A200）作为纳米骨架,通过调节载体和骨架材料的类型和比例筛选出具有pH 1.2、6.8敏感释放行为的纳米骨架载体处方,考察缬沙坦在pH 1.2、6.8环境中释放和在大鼠体内的药动学行为特征。结果 筛选的pH 1.2敏感释放缬沙坦NDDS处方缬沙坦、S350、E100比例为1∶3∶1,pH 6.8敏感释放缬沙坦NDDS处方为缬沙坦、A200、L100-55比例为1∶1∶3。pH 6.8敏感释放处方可调控缬沙坦在肠道pH 6.8条件下特异性溶出;pH 1.2敏感释放处方在保持缬沙坦在pH 6.8高溶出特性的同时可特异性地提高胃部酸性条件下的药物释放。pH 1.2、6.8敏感释放缬沙坦NDDS均一定程度上改善了缬沙坦的生物利用度,其中pH 6.8敏感释放缬沙坦NDDS提高生物利用度的幅度更高,血药浓度变化比较平缓。结论 NDDS可以调控缬沙坦的体外溶出和生物利用度,有望应用于pH值敏感性难溶药物的递送。     

The effects of casein on diclofenac release from hydroxypropylmethylcellulose (HPMC) compacts

The inclusion of casein, either as the acid or sodium salt form, was found to significantly modify the release of the acidic drug diclofenac from hydroxypropylmethycellulose (HPMC, Methocel grades K100LV and K15M)-based matrices. The presence of casein in diclofenac-K100LV matrices increased the drug release rate and rendered the release profile more linear. Furthermore, sodium caseinate appeared to retard the disintegrating tendency of the higher molecular weight HPMC-drug systems, apparently by enhancing the initial gel forming ability of these systems. Surprisingly, dissolution profiles of the salt and acid forms of the drug were similar when co-compressed with sodium caseinate, and addition of HPMC retarded release of both forms of drug to the same extent. Swelling and erosion experiments indicated that the presence of casein decreased the extent of medium uptake (swelling) of the matrices and accelerated the rate of erosion, while not altering the dissolution medium infiltration rate. Phase solubility analysis indicated that the solubility of the drug was also enhanced by sodium caseinate, consistent with complex formation between the drug and casein.     

Solid dispersion of hydroxypropyl beta-cyclodextrin and ketorolac: enhancement of in-vitro dissolution rates, improvement in anti-inflammatory activity and reduction in ulcerogenicity in rats

Ketorolac, is a non-steroidal anti-inflammatory drug, with strong analgesic activity. It is practically insoluble in water and has been implicated in causing gastrointestinal ulceration. This study describes the formulation of solid dispersions of ketorolac using hydroxypropyl beta-cyclodextrin (HPbeta-CyD) and beta-cyclodextin (beta-CyD) as carriers, to improve the aqueous solubility of the drug, thus enhancing its bioavailability. Also, reduction in ulcerogenicity was anticipated. Differential scanning calorimetry and X-ray diffraction studies indicated loss of crystalline nature of the drug, in the dispersions prepared with HPbeta-CyD. NMR studies revealed a strong interaction between drug and HPbeta-CyD. Solid dispersions of drug with beta-CyD retained the crystalline nature of the drug. All the solid dispersions showed a remarkable improvement in the rate and extent of dissolution of ketorolac. The kneaded dispersion with HPbeta-CyD prepared using a 1:1 alcohol-water mixture showed promise in reducing the ulcer-inducing effect of ketorolac in rats. Oral administration of this dispersion was found to inhibit carrageenan-induced paw oedema in rats to a significantly greater extent compared with ketorolac or its trometamol salt. Though beta-CyD as a carrier for ketorolac gave faster release of the poorly soluble drug, HPbeta-CyD proved to be superior to beta-CyD, as a carrier in the kneaded dispersion prepared using 1:1 alcohol-water mixture. These results suggest that solid dispersions of ketorolac with HPbeta-CyD aid in faster dissolution and better bioavailability of the drug. The higher solubility of the drug in the presence of HPbeta-CyD also reduces local gastrointestinal side-effects of the drug.     

Palatable reconstitutable dry suspension of artemether for flexible pediatric dosing using cyclodextrin inclusion complexation

The present research was conducted to investigate the inclusion complexation of artemether (ARM) with beta-cyclodextrin (CD) with the aim of masking the bitterness along with improving the drug release and preparing a stable palatable formulation of ARM especially for pediatrics. A physical mixture and kneaded system were prepared to study the inclusion complexation. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and scanning electron microscopy (SEM) were performed to identify the physicochemical interaction between drug and carrier, hence its effect on drug release. Reconstitutable dry suspension was evaluated for angle of repose, sedimentation characterization and pH. In vitro drug release studies for physical mixture and kneaded system were performed at pH, 1.2 and 6.8. Bitterness score was evaluated using gustatory sensation test. The FTIR, DSC and XRPD studies indicated inclusion complexation in physical mixture and kneaded system. In addition, physical mixture and kneaded system exhibited improved drug release at pH, 1.2 and 6.8. To formulate palatable reconstitutable dry suspension of ARM, the 1:20M physical mixture was selected based on bitterness score. Reconstitutable dry suspension prepared using physical mixture (DS4), showed complete bitter taste masking, good flowability and ease of redispersibility. Taste evaluation of reconstitutable dry suspension in human volunteers rated tasteless with a score of 0 to DS4 and 3 to DS5 (reconstitutable dry suspension prepared using pure ARM). This conclusively demonstrated a stable and palatable reconstitutable dry suspension of ARM using CD inclusion complexation for flexible pediatric dosing.     

Palatable reconstitutable dry suspension of artemether for flexible pediatric dosing using cyclodextrin inclusion complexation

The present research was conducted to investigate the inclusion complexation of artemether (ARM) with beta-cyclodextrin (CD) with the aim of masking the bitterness along with improving the drug release and preparing a stable palatable formulation of ARM especially for pediatrics. A physical mixture and kneaded system were prepared to study the inclusion complexation. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and scanning electron microscopy (SEM) were performed to identify the physicochemical interaction between drug and carrier, hence its effect on drug release. Reconstitutable dry suspension was evaluated for angle of repose, sedimentation characterization and pH. In vitro drug release studies for physical mixture and kneaded system were performed at pH, 1.2 and 6.8. Bitterness score was evaluated using gustatory sensation test. The FTIR, DSC and XRPD studies indicated inclusion complexation in physical mixture and kneaded system. In addition, physical mixture and kneaded system exhibited improved drug release at pH, 1.2 and 6.8. To formulate palatable reconstitutable dry suspension of ARM, the 1:20M physical mixture was selected based on bitterness score. Reconstitutable dry suspension prepared using physical mixture (DS4), showed complete bitter taste masking, good flowability and ease of redispersibility. Taste evaluation of reconstitutable dry suspension in human volunteers rated tasteless with a score of 0 to DS4 and 3 to DS5 (reconstitutable dry suspension prepared using pure ARM). This conclusively demonstrated a stable and palatable reconstitutable dry suspension of ARM using CD inclusion complexation for flexible pediatric dosing.     

Drug formulations intended for the global market should be tested for stability under tropical climatic conditions

RATIONALE OBJECTIVE: The quality of drugs imported into developing countries having a tropical climate may be adversely affected if their formulations have not been optimized for stability under these conditions. The present study investigated the influence of tropical climate conditions (class IV: 40 degrees C, 75% relative humidity) on the drug content, in vitro dissolution and oral bioavailability of different formulations of two essential drugs marketed in Tanzania: diclofenac sodium and ciprofloxacin tablets. METHODS: Before and after 3 and 6 months storage under class IV conditions the drug content and in vitro dissolution were evaluated using United States Pharmacopoeia (USP) 24 methods. Following a randomized four-period cross-over study, the pharmacokinetic parameters of drug formulations stored for 3 months under class IV conditions were compared with those stored at ambient conditions. RESULTS: Drug content and drug release from all tested ciprofloxacin formulations were within USP-24 requirements and remained stable during storage at simulated tropical conditions. Oral bioavailability was also not influenced by tropical conditions. The dissolution rate of two diclofenac formulations (Diclo 50 manufactured by Camden and Dicloflame 50 manufactured by Intas) reduced significantly during storage under class IV conditions. After oral administration Camden tablets stored for 3 months under class IV conditions showed a reduction in C(max) (90% CI of C(max) ratio: 0.59 - 0.76). This reduction was smaller than expected based on the in vitro tests. CONCLUSIONS: Some drug formulations imported into Tanzania are not optimized for stability in a tropical climate. Manufacturers and regulatory authorities should pay more attention to the WHO recommendations for testing the stability of drugs under tropical climate conditions. Efforts should be made to improve the in vitro tests to better predict the bioavailability.     

Biowaiver monographs for immediate release solid oral dosage forms: diclofenac sodium and diclofenac potassium

Literature data are reviewed regarding the scientific advisability of allowing a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing either diclofenac potassium and diclofenac sodium. Within the biopharmaceutics classification system (BCS), diclofenac potassium and diclofenac sodium are each BCS class II active pharmaceutical ingredients (APIs). However, a biowaiver can be recommended for IR drug products of each salt form, due to their therapeutic use, therapeutic index, pharmacokinetic properties, potential for excipient interactions, and performance in reported BE/bioavailability (BA) studies, provided: (a) test and comparator contain the same diclofenac salt; (b) the dosage form of the test and comparator is identical; (c) the test product contains only excipients present in diclofenac drug products approved in ICH or associated countries in the same dosage form, for instance as presented in this paper; (d) test drug product and comparator dissolve 85% in 30 min or less in 900 mL buffer pH 6.8, using the paddle apparatus at 75 rpm or the basket apparatus at 100 rpm; and (e) test product and comparator show dissolution profile similarity in pH 1.2, 4.5, and 6.8.     

The role of the kneading paddle and the effects of screw revolution speed and water content on the preparation of solid dispersions using a twin-screw extruder

The twin-screw hot-melt extrusion process is useful for preparing solid dispersions which can improve the dissolution and absorption of drugs. The kneading paddle elements of the screws play an important role in changing the crystallinity and dissolution properties of a solid dispersion of kneaded nifedipine-hydroxypropylmethylcellulose phthalate (NP-HPMCP). After operating the machine, a small amount of kneaded material adhering to the screws was collected and its physicochemical properties examined. Samples from the kneading paddle with a twist angle of 60 degrees were transparent and exhibited super-saturation on dissolution testing. When the kneading paddle elements were detached from the screws and only the feed screw elements were operated, the physicochemical properties of the extruded material were significantly influenced by the operating conditions of the machine e.g. revolution rate of screws, and the amount of water added to the feed materials. Slow revolution of the screws and the addition of a suitable amount of water to the mixture increased the rate of drug dissolution, although no super-saturation occurred. As the kneading paddle elements can retain the mixture in the machine for a longer period under intense shear, desired solid dispersions can be prepared routinely irrespective of the operating conditions. Moreover, a capillary rheometer can be useful to predetermine the amount of water added and the temperature for the preparation of solid dispersions using a twin-screw extruder.     

Encapsulation of poorly soluble basic drugs into enteric microparticles: a novel approach to enhance their oral bioavailability

Poorly water soluble basic drugs are very sensitive to pH changes and following dissolution in the acidic stomach environment tend to precipitate upon gastric emptying, which leads to compromised or erratic oral bioavailability. In this work, we show that the oral bioavailability of a model poorly soluble basic drug (cinnarizine) can be improved by drug encapsulation within highly pH-responsive microparticles (Eudragit L). The latter was prepared by emulsion solvent evaporation which yielded discrete spherical microparticles (diameter of 56.4 ± 6.8 μm and a span of 1.2 ± 0.3). These Eudragit L (dissolution threshold pH 6.0) microparticles are expected to dissolve and release their drug load at intestinal conditions. Thus, the enteric microparticles inhibited the in vitro release of drug under gastric conditions, despite high cinnarizine solubility in the acidic medium. At intestinal conditions, the particles dissolved rapidly and released the drug which precipitated out in the dissolution vessel. In contrast, cinnarizine powder showed rapid drug dissolution at low pH, followed by precipitation upon pH change. Oral dosing in rats resulted in a greater than double bioavailability of Eudragit L microparticles compared to the drug powder suspension, although C_max and T_max were similar. The higher bioavailability with microparticles contradicts the in vitro results. Such an example highlights that although in vitro results are an indispensable tool for formulation development, an early in vivo assessment of formulation behaviour can provide better prediction for oral bioavailability.     

Dissolution properties and bioavailability of ground mixture of N,N-dimethylcarbamoylmethyl alpha, 2-dimethyl-5H-[1]benzopyrano[2,3-b]-pyridine-7-acetate with various pharmaceutical ingredients

Ground mixture of N,N-dimethylcarbamoylmethyl alpha, 2-dimethyl-5H-[1]benzopyrano-[2,3-b]pyridine-7-acetate (1) with various pharmaceutical ingredients were prepared in order to investigate their dissolution behaviors and bioavailability. Taking into account the weakly basic property of 1, the dissolution rate was determined in the 2nd fluid (pH 6.8) of disintegration test, JP XI. Dissolution rates of the ground mixtures (1 : 1, w/w) of 1 with hydroxypropylcellulose-L (HPC-L), low substituted hydroxypropylcellulose (L-HPC) or lactose respectively, showed a significant increase compared with compound 1 alone. Three kinds of experimental fine granules were prepared; type A: produced from ground mixture of 1, HPC-L, L-HPC and lactose; type B: produced from physical mixture having the same composition as type A; type C: produced 1, L-HPC and lactose. In these fine granules, only type A exhibited pH-independent dissolution profiles. Bioavailability study was carried out in beagle dogs whose gastric acidity was controlled in advance to low levels by administration of omeprazole. The test was conducted in a cross over design. Reflecting their dissolution characteristics, type A granules showed better bioavailability than the others. These results suggest that grinding is useful for the improvement of the dissolution property and bioavailability of 1, a weakly basic compound.     

Influence of surfactants (present in the dissolution media) on the release behaviour of tolbutamide from its inclusion complex with beta-cyclodextrin.

The possible competitive displacement of a drug from its cyclodextrin-based inclusion complex by a third substance was investigated by studying the dissolution behaviour of tolbutamide-beta-cyclodextrin inclusion complex in demineralised water and in aqueous solution of different surfactants. Physical mixtures and kneaded systems were prepared in 1:1 and 1:2 drug-beta-cyclodextrin mol/mol ratios and they were characterised by hot-stage microscopy, differential scanning calorimetry, and X-ray powder diffractometry. The release behaviour of tolbutamide from its inclusion complex was studied by studying the dissolution of the binary systems in water and in aqueous solutions of three surfactants: polysorbate 20, poloxyl 23-lauryl ether, and sodium lauryl sulphate. When demineralised water was used as the dissolution media, the fastest dissolution of tolbutamide was obtained from 1:2 kneaded system followed by 1:1 kneaded system. The presence of poloxyl 23-lauryl ether and sodium lauryl sulphate in the media caused a decrement in the rate and extent of dissolution of the drug from both kneaded systems in comparison with that obtained from the same systems in water. However, the release of tolbutamide from the kneaded systems remains unaffected when polysorbate 20 was present in the dissolution media. Results of this study suggest that the simultaneous presence of beta-cyclodextrin and surfactants of proper molecular structure in a pharmaceutical formulation can give rise to an unexpected dissolution of the drug.     

呋喃妥因肠溶微囊体外溶出试验及人体内生物利用度研究

本文考察了呋喃妥因肠溶微囊的体外溶出行为,用尿药法研究了其人体内的生物利用度并与市售肠溶片进行比较。体外溶出试验结果表明呋喃妥因肠溶微囊于人工胃液中药物释放降低,人工肠液中快速释放。肠溶微囊人体内生物利用度明显高于市售片。     

In vitro and in vivo evaluation of oral tablet formulations prepared with ketoconazole and hydroxypropyl-β-cyclodextrin

The objective of this study was to enhance the solubility, dissolution rate, and oral bioavailability of a very poorly water-soluble anti-fungal agent, ketoconazole (KET), by inclusion complexation with a highly-soluble cyclodextrin derivative, hydroxypropyl-β cyclodextrin (HP-β-CD). Two groups of tablets containing KET alone and KET:HP-β-CD (1:2) kneaded product (KP) including magnesium stearate and lactopress (anhydrous and spray-dried) as excipients were prepared by direct compression method. After the characterization studies, the in vitro dissolution studies of these tablets in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) were carried out. To evaluate the in vivo bioavailability, the tablets were administered orally to rabbits and drug levels in serum were determined by HPLC. Tablets containing the cyclodextrin complex showed a higher in vitro dissolution rate and bioavailability compared to the tablets containing KET alone.     

Design of pH-independent controlled release matrix tablets for acidic drugs

The rate and extent of drug release from most controlled release systems are influenced by the pH of the dissolution medium for drugs with pH-dependent solubility. This dependency of drug release on pH may lead to additional inter- and intra-subject variability in drug absorption. In the present study, a pH-independent controlled release matrix system for acidic drugs was designed by incorporating release-modifiers in the formulation. Controlled release matrix tablets were prepared by compression of divalproex sodium, Methocel K4M and Eudragit E 100 or Fujicalin as the release-modifier. For formulations without any release-modifier, the extent and rate of drug release at pH 6.8 was much higher than that at pH 1.0. Formulations containing Eudragit E 100 provided drug release that was essentially independent of pH. This was achieved because Eudragit E 100 significantly increased the drug release in acidic medium and slightly decreased the release rate at higher pH. The increased release in the acidic medium can be attributed to the elevation of the micro-environmental pH in the swollen polymer gel layer. Formulations containing Fujicalin were less effective than those containing Eudragit E 100. This was attributed to the relative inability to elevate the pH and shorter residence time of Fujicalin in the matrix relative to Eudragit E 100.     

新药开发中药物的盐型选择

成盐是改善弱酸性及弱碱性药物的溶解度和提高药物生物利用度的重要手段.因此,为药物筛选合适的反离子是药品研发过程的关键步骤.本文探讨了筛选反离子时需考虑的因素和成盐对药物的溶解度和溶出速率的影响.     

Release behaviour of diclofenac sodium dispersed in Gelucire® and encapsulated with alginate beads

Sustained release polymeric particles containing diclofenac sodium dispersed in Gelucire® matrix and encapsulated in calcium alginate shell were prepared with different drug-to-polymer ratios and also with different concentrations of sodium alginate for a fixed drug-to-polymer ratio in an aqueous environment. Spherical particles were formed by dropping an emulsion of diclofenac sodium in Gelucire® matrix, emulsified with sodium alginate, into calcium chloride solution. The gelled beads formed by ionotropic gelation of alginate with calcium ions showed sustained release of the water soluble drug in in-vitro release study. Drug release was a function of square-root of time, suggesting a matrix diffusion release pattern. The rate of release was significantly suppressed with increasing proportions of Gelucire® in the mixture. Sustained and complete release was achieved with Gelucire® of low melting point and low HLB value. No significant drug release occurred in a dissolution medium of pH 1.5, whereas complete release was observed at pH 6.8, consistent with considerable swelling of the alginate gel at this pH.     

Enhancement of the dissolution rate and oral absorption of a poorly water soluble drug by formation of surfactant-containing microparticles

The slow dissolution rate exhibited by poorly water-soluble drugs is a major challenge in the drug development process. Following oral administration, drugs with slow dissolution rates generally show erratic and incomplete absorption which may lead to therapeutic failure. The aim of this study was to improve the dissolution rate and subsequently the oral absorption and bioavailability of a model poorly water-soluble drug. Microparticles containing the model drug (griseofulvin) were produced by spray drying the drug in the absence/presence of a hydrophilic surfactant. Poloxamer 407 was chosen as the hydrophilic surfactant to improve the particle wetting and hence the dissolution rate. The spray dried particles were characterized and in vitro dissolution studies and in vivo absorption studies were carried out. The results obtained showed that the dissolution rate and absolute oral bioavailability of the spray dried griseofulvin/Poloxamer 407 particles were significantly increased compared to the control. Although spray drying griseofulvin alone increased the drug's in vitro dissolution rate, no significant improvement was seen in the absolute oral bioavailability when compared to the control. Therefore, it is believed that the better wetting characteristics conferred by the hydrophilic surfactant was responsible for the enhanced dissolution rate and absolute oral bioavailability of the model drug.     

Enhanced dissolution and bioavailability of biochanin A via the preparation of solid dispersion: in vitro and in vivo evaluation

The present study aimed to improve the bioavailability of biochanin A, a poorly soluble bioflavonoid, via the preparation of solid dispersion (SD) using Solutol HS15 and HPMC 2910. Solubility of biochanin A was enhanced by 8-60 folds as the drug-carrier ratio was increased in SDs. Furthermore, compared to pure biochanin A or physical mixture (PM), SDs significantly improved the dissolution rate and the extent of drug release. Particularly, SDs (Drug:Solutol HS15:HPMC 2910=1:5:5 or 1:10:10) achieved the rapid and complete drug release (approximately 100% within 1h) at pH 6.8. The XRD patterns indicated that SDs might enhance the solubility of biochanin A by changing the drug crystallinity to amorphous state in addition to the solubilizing effect of hydrophilic carriers. The improved dissolution of biochanin A via SD formulation appeared to be well correlated with the enhanced oral exposure of biochanin A in rats. After an oral administration of SD (Drug:Solutol HS15:HPMC 2910=1:10:10), C(max) and AUC of biochanin A were increased by approximately 13 and 5 folds, respectively, implying that SDs could be effective to improve the bioavailability of biochanin A. In conclusion, solid dispersion with Solutol HS15 and HPMC 2910 appeared to be promising to improve the dissolution and oral exposure of biochanin A.