Overexpression of the transcription factor MdWRKY115 improves drought and osmotic stress tolerance by directly binding to the MdRD22 promoter in apple

Abiotic stress reduces plant yield and quality.WRKY transcription factors play key roles in abiotic stress responses in plants,but the molecular mechanisms by which WRKY transcription factors mediate responses to drought and osmotic stresses in apple(Malus×domestica Borkh.)remain unclear.Here,we functionally characterized the apple GroupⅢWRKY gene MdWRKY115.qRT-PCR analysis showed that MdWRKY115 expression was up-regulated by drought and osmotic stresses.GUS activity analysis revealed that the promoter activity of MdWRKY115 was enhanced under osmotic stress.Subcellular localization and transactivation assays indicated that MdWRKY115 was localized to the nucleus and had a transcriptional activity domain at the N-terminal region.Transgenic analysis revealed that the overexpression of MdWRKY115 in Arabidopsis plants and in apple callus markedly enhanced their tolerance to drought and osmotic stresses.DNA affinity purification sequencing showed that MdWRKY115 binds to the promoter of the stress-related gene MdRD22.This binding was further verified by an electrophoretic mobility shift assay.Collectively,these findings suggest that MdWRKY115 is an important regulator of osmotic and drought stress tolerance in apple.

The CBL-interacting protein kinase OsCIPK1 phosphorylated by SAPK10 positively regulates responses to ABA and osmotic stress in rice

SubclassⅢsucrose nonfermenting1-related protein kinase 2s(SnRK2s)function in ABA and abiotic stress responses by unknown mechanisms.We found that osmotic stress/ABA-activated protein kinase 10(SAPK10),a member of rice SnRK2s,physically interacted with CBL-interacting protein kinase 1(OsCIPK1).OsCIPK1 expression was up-regulated by ABA and PEG treatment,and overexpression increased the ABA sensitivity of seed germination and root growth and plant osmotic stress tolerance.Osmotic stress or ABA-induced activation of OsCIPK1 is dependent on SAPK10.SAPK10 phosphorylates Thr-24 of OsCIPK1 in vitro,and this phosphorylation increases the activity of OsCIPK1 and positively regulates the function of OsCIPK1 in ABA responses and plant osmotic stress tolerance.This study suggests that OsCIPK1 is a direct phosphorylated substrate of SAPK10,and SAPK10-mediated phosphorylation of OsCIPK1 functions in ABA signaling and increases rice osmotic stress tolerance.

JA-mediated MYC2/LOX/AOS feedback loop regulates osmotic stress response in tea plant

Osmotic stress caused by low-temperature,drought and salinity was a prevalent abiotic stress in plant that severely inhibited plant development and agricultural yield,particularly in tea plant.Jasmonic acid(JA)is an important phytohormone involving in plant stress.However,underlying molecular mechanisms of JA modulated osmotic stress response remains unclear.In this study,high concentration of mannitol induced JA accumulation and increase of peroxidase activity in tea plant.Integrated transcriptome mined a JA signaling master,MYC2 transcription factor is shown as a hub regulator that induced by mannitol,expression of which positively correlated with JA biosynthetic genes(LOX and AOS)and peroxidase genes(PER).CsMYC2 was determined as a nuclei-localized transcription activator,furthermore,ProteinDNA interaction analysis indicated that CsMYC2 was positive regulator that activated the transcription of CsLOX7,CsAOS2,CsPER1 and CsPER3via bound with their promoters,respectively.Suppression of CsMYC2 expression resulted in a reduced JA content and peroxidase activity and osmotic stress tolerance of tea plant.Overexpression of CsMYC2 in Arabidopsis improved JA content,peroxidase activity and plants tolerance against mannitol stress.Together,we proposed a positive feedback loop mediated by CsMYC2,CsLOX7 and CsAOS2 which constituted to increase the tolerance of osmotic stress through fine-tuning the accumulation of JA levels and increase of POD activity in tea plant.

Impact of Osmotic Pressure on Seepage in Shale Oil Reservoirs

Following large-scale volume fracturing in shale oil reservoirs,well shut-in measures are generally employed.Laboratory tests and field trials have underscored the efficacy of fracturing fluid imbibition during the shut-in phase in augmenting shale oil productivity.Unlike conventional reservoirs,shale oil reservoirs exhibit characteristics such as low porosity,low permeability,and rich content of organic matter and clay minerals.Notably,the osmotic pressure effects occurring between high-salinity formation water and low-salinity fracturing fluids are significant.The current understanding of the mobilization patterns of crude oil in micro-pores during the imbibition process remains nebulous,and the mechanisms underpinning osmotic pressure effects are not fully understood.This study introduces a theoretical approach,by which a salt ion migration control equation is derived and a mathematical model for spontaneous imbibition in shale is introduced,which is able to account for both capillary and osmotic pressures.Results indicate that during the spontaneous imbibition of low-salinity fluids,osmotic effects facilitate the migration of external fluids into shale pores,thereby complementing capillary forces in displacing shale oil.When considering both capillary and osmotic pressures,the calculated imbibition depth increases by 12%compared to the case where only capillary forces are present.The salinity difference between the reservoir and the fracturing fluids significantly influences the imbibition depth.Calculations for the shutin phase reveal that the pressure between the matrix and fractures reaches a dynamic equilibrium after 28 days of shut-in.During the production phase,the maximum seepage distance in the target block is approximately 6.02 m.

Long-term decay of the water pressure in the osmotic tensiometer

Matric suction is an important state variable required for the assessment of unsaturated soil properties.Tensiometers are commonly used for direct matric suction measurement but have a limited measuring range up to 90 kPa due to the cavitation problem.Osmotic tensiometer(OT)can improve the measuring range of tensiometers by increasing the osmotic pressure of water to avoid the cavitation.However,the long-term water pressure decay that appeared in OTs caused a gradual decrease in their measuring range.In this study,crosslinked poly(acrylamide-co-acrylic acid)potassium salt(PAM-co-PAAK)was used for the preparation of OTs(five in total)to explore the mechanism of water pressure decay of OTs.The maximum water pressure in the OT versus the volume fraction of polymer filled in the OT was described based on the Flory-Huggins polymer theories and validated using WP4C dewpoint hygrometer.The long-term pressure decay of OT-1,OT-2,and OT-3 was observed for 130 d and constant pressures were found for OT-1 and OT-2,indicating that the pressure decay of OT was mainly caused by the stress relaxation of the polymer hydrogels,and standard linear solid(SLS)rheological model was appropriate to fit the decay data.For OT-1,OT-2 and OT-3,the theoretical osmotic pressure that was calculated based on the mass of retrieved polymer from OTs after 130-d pressure observation was higher than the actual osmotic pressure as observed,indicating that polymer leakage cannot explain the pressure decay of the OT.The ultravioletevisible(UVevisible)spectrophotometry examined the change in polymer concentrations in the water containers of OT-4 and OT-5 and demonstrated that there was no increase in polymer leakage during the period of pressure decay of OT-4 and OT-5.As a result,the pressure decay of OT was not caused by polymer leakage.The results of this research suggested that the viscoelastic properties of polymers should be taken into consideration in further OT development.

Adaptive strategy of Nitraria sibirica to transient salt,alkali and osmotic stresses via the alteration of Na+/K+fluxes around root tips

Nitraria sibirica Pall.is an important shrub with a strong salt-alkali tolerance,but the mechanism underlying this tolerance remains obscure.In this study,N.sibirica,with salt-sensitive Vigna radiata(Linn.)Wilczek as the control,was subjected to transient salt stress(100 mM NaCl),alkali stress(50 mM Na_(2)CO_(3)),and osmotic stress(175 mM mannitol).The ionic fluxes of Na^(+)and K^(+)in the root apical region were measured.Results show that,under salt and alkali stress,N.sibirica roots exhibited higher capacities to limit Na+influx and reduce K+efflux,thereby resulting in lower Na^(+)/K^(+)ratios compared with V.radiata roots.Alkali stress induced stronger Na^(+)influx and K+efflux in the root salt stress treatment;Na^(+)influx was mainly observed in the root cap,while K^(+)efflux was mainly observed in the elongation zone.While under osmotic stress,N.sibirica roots showed stronger Na+efflux and weaker K+efflux than V.radiata roots.Na+efflux was mainly observed in the root elongation zone,while K+efflux was in the root cap.These results reveal the ionic strategy of N.sibirica in response to transient salt,alkali,and osmotic stresses through the regulation of Na+/K+flux homeostasis.

Effect of Osmotic Stress with PEG6000 on Osmotic Adjustment Solute in Seedling Leaves of Chenopodium album L.

[ Objective] The purpose was to discuss drought resistance mechanism of Chenopodium album L. and supply theoretical basis and practical guidance for artificial cultivation and popularization of C. album. [ Method] C. album seedlings grown to 6th leaf stage were conducted osmotic stress treatment with PEG6000 osmotic whose concentration was set up as 0, 5%, 10% and 20% and the various physiological indices of the 3rd -5th function leaves in upper plant were determined after being treated for 0, 1,3, 5, 7 and 9 d. [ Result] Under osmotic stress with 5% PGE, the relative water content （RWC） of C. album reduced less. Under osmotic stress with 10%, the RWC in seedling leaves of C. album decreased to 62% on the fifth day and the leaves began to wither. Under osmotic stress with 20%, the RWC in seedling leaves of C. album decreased to 61.9% on the third day and the leaves appeared withering, and the RWC decreased to 48.6% on the 7th day and the leaves were dry and yellow. Proline contents in seedling leaves of C. album under osmotic stress with 5%, 10% and 20% PEG were 7.64, 10.9 and 29.4 times of CK on the 7th day. [ Conclusion] C. album hed some adaptability to moderate osmotic stress, but the PEG osmotic stress with high concentration and long time might lead to severe damage on C. album.

Effects of Nitric Oxide on the Germination of Wheat Seeds and Its Reactive Oxygen Species Metabolisms Under Osmotic Stress

Effects of sodium nitroprusside (SNP), a nitric oxide (NO) donor, on the germination and metabolism of reactive oxygen species were surveyed in wheat (Triticum aestivum L.) seeds. Germination of wheat seeds and even the elongation of radicle and plumule were dramatically promoted by SNP treatments during the germination under osmotic stress. Meanwhile, activities of amylase and EP were enhanced, thus leading to the degradation of storage reserve in seeds. After osmotic stress was removed, higher viability of wheat seeds was also maintained. In addition, the activities of CAT, APX and the content of proline were increased by SNP treatment simultaneously, but activities of LOX were inhibited, and both of which were beneficial for improving the antioxidant capacity during the germination of wheat seeds under osmotic stress. It was also shown that the increase of the activity of amylase induced by SNP in embryoless half-seeds of wheat in the beginning period of germination (6 h) might be indirectly related to GA(3).

Effects of Polyamine on Leaf Physiological and Biochemical Indexes of Maize Seedlings under Osmotic Stress

[Objective]The research aimed to probe into the mechanism of polyamine enhancing the tolerance of plants to drought stress and provide theoretical basis for application of polyamine in process of maize drought resistance. [Method]With PEG-6000 simulating natural drought,the change in content of soluble protein and relative water content were investigated in seedling leaves of two maize cultivars,Nongda 108 and Yedan 13 under osmotic stress with exogenous Spd treatment. [Result]On the 7th day,leaf relative water content and the content of soluble protein decreased more significantly in leaves of Yedan 13 （drought-sensitive） than in Nongda 108 （drought-tolerant）. Exogenous Spd treatment not only obviously inhibited the decrease of leaf relative water content,but also increased the content of soluble protein. [Conclusion]Exogenous Spd treatment could enhance the tolerance of maize seedlings to osmotic stress,via improving the content of soluble protein in seedling leaves.

Response of Photosynthesis, Growth, Carbon Isotope Discrimination and Osmotic Tolerance of Rice to Elevated CO_2

Four rice ( Oryza sativa L.) cultivars 'IR72', 'Tesanai 2', 'Guichao 2' and 'IIyou 4480' were grown in two plastic house (15 m×3 m) with 35 μmol/mol and 60 μmol/mol CO 2 concentration which was controlled by computer. As compared with rice at ambient 35 μmol/mol CO 2, the changes in photosynthetic rate at elevated CO 2 showed up_regulation ('IR72' and 'Tesanai 2'), stable (unchanged) in 'Guichao 2' and down_regulation type ('IIyou 4480'). Growth rate, panicle weight, integrated water use efficiency (WUE) calculated from Δ 13 C and the capacity of scavenging DPPH · (1,1_diphenyl_2_picrylhydrazyl) free radical were increased at elevated CO 2. An increment in total biomass was observed in three cultivars by elevated CO 2, with the exception of 'IIyou 4480'. Ratios of panicle weight/total biomass were altered to different extents in tested cultivars by elevated CO 2. When leaf segments were subjected to PEG osmotic stress, the electrolyte leakage rate from leaves grown at elevated CO 2 was less than that at 35 μmol/mol CO 2. Those intraspecific variations of rice imply a possibility for selecting cultivars with maximal productivity and high tolerance to stresses adapted to elevated CO 2 in the future.

Effects of Drought Stress on Osmotic Regulation Substances of Five Catalpa bungei Clones

[Objective] This study aimed to investigate the effects of drought stress on osmotic regulation substances of Catalpa bungei clones. [Method] Potting experimental was carried out with plastic film sealing method, to differentiate the degrees of drought stress based on changes in soil water content and leaf water potential and investigate variations in contents of osmotic regulation substances（free proline,soluble sugar and soluble protein） in leaves of five Catalpa bungei clones under different degrees of drought stresses. [Result] According to changes in soil water content and leaf water potential, the whole process of drought stress was divided into normal level（CK, with soil water content of 97.49% and leaf water potential of-0.54MPa）, light drought（LD with soil water content of 59.96% and leaf water potential of-1.28 MPa）, mediate drought（MD with soil water content of 34.19% and leaf water potential of-2.32 MPa） and severe drought（SD with soil water content of 14.52%and leaf water potential of-2.99 MPa）. The soil water content and leaf water potential of five Catalpa bungei clones reached the highest correlation in exponential fitting, with an average R2of 0.989 3（P0.001）. The free proline content in leaves of five Catalpa bungei clones increased rapidly with the increasing degree of drought stress（P 0.001）. To be specific, free proline contents of Catalpa bungei clones015-1 and 7080 were 34.39 and 33.41 times of the normal level under severe drought conditions, which reached an extremely significant level（P0.001）; the free proline content of Catalpa bungei clone 1-3 rapidly increased to（855.46±227.52） μg/g Fw under light drought conditions. The soluble protein content in leaves showed different variation trends. To be specific, the soluble protein content of Catalpa bungei clone 7080 was the lowest at various drought stages and reached（1.644 ±0.137）mg/g Fw under normal conditions; the soluble protein content of Catalpa bungei clone 1-3 was relatively high under normal conditions and was reduced rapidly under light drought conditions, showing different response patterns. [Conclusion] Osmotic regulation substances in leaves of five Catalpa bungei clones all have certain response to drought stress. Free proline is the most important osmotic regulation substance, followed by soluble protein, while soluble sugar makes no significant contribution. According to changes in content of osmotic regulation substances, Catalpa bungei clone 7080 has relatively high capacity and good drought resistance, while Catalpa bungei clone 1-3 has the rapidest response to drought stress.

Mechanism of Drug Release from Compound Metformin/Glipizide Elementary Osmotic Pump Tablets

In previous studies, compound mefformin/glipizide was developed. Aim To discover the mechanism of drug release from factors influencing drug release from dosage form （the semi-permeable cry orifice） were investigated. Results The influx of water that elementary osmotic pump tablet it. Methods Three rate-limiting membrane, tablet core and delivpassed the osmotic pump tablet was almost equal to the metformin release rate, while it was greatly less than the drug dissolution rate from tablet core. The size of orifice from 0. 4 mm to 0.8 mm had no influence on drug release. The osmotic pressure of tablet core was mainly caused by mefformin. Conclusion From the developed model of osmotic pump systems, it can be seen that only the water influx through the membrane is a rate-limiting step, not tablet core dissolution rate and solution influx, and only when the core dissolution rate is equal to the solution influx, the zero order release is seen in the osmotic pump systems.

OSMOTIC STRESS DECREASES THE ACTIVITY OF ATPASE ASSOCIATED WITH THE ROOT CAP PLASMODESMATAIN ZEA MAYS

With light and electron microscopy the substructural change and the ATPase activity of corn (Zea mays L.) root cap cells after short-term osmotic stress were studied. Some spoke-like fine strands originating from the departed periplasm and stretching towards cell wall could be observed even after plasmolysis. By observing the precipitation of ATPase activity product (lead phosphate) at plasma membrane and plasmodesmata, it was found that the fine strands were plasma membrane-lined channels surrounding the cytoplasm and that they still firmly connected to the plasmodesmata during plasmolysis. Compared with the control (unstressed), a sharp decrease of ATPase activity in the plasmodesmata of the stressed cells was observed. Inhibition of energy metabolism in these limited locales would affect the physiological activity, maybe including the regulation of permeability and the change of size exclusion limit (SEL) of plasmodesmata.

Relationship between ATPase activity and conjugated polyamines in mito-chondrial membrane from wheat seedling roots under osmotic stress

The effects of osmotic stress on the ATPase activity, the contents of —SH group and conjugated polyamines in mitochondrial membrane from wheat seedling [Triticum aestivum L. cv. Yumai No.18(drought-tolerant) and cv. Yumai No.9(drought-sensitive)] roots were investigated. The results showed that ATPase activity and —SH group content decreased with polyethylene glycol(PEG) 6000(-0.55 MPa) treatment for 7 d, in concert with the decrease of the ratio of noncovalently conjugated spermidine(NCC-Spd)/noncovalently conjugated putrescine(NCC-Put) and increase of the covalently conjugated putrescine(CC-Put). Osmotic stress injury to Yangmai No.9 seedlings was alleviated greatly with 1 mmol/L exogenous spermidine(Spd), in concert with marked increases of the ratio of NCC-Spd/NCC-Put, —SH group contents and ATPase activity in mitochondrial membrane. Under osmotic stress, the concomitant treatment of Yumai No.18 seedlings with methylglyoxyl bis(guanylhydrazone) (MGBG), an inhibitor of S-adenosyl methionine decarboxylase(SAMDC), and phenanthrolin (o-Phen), an inhibitor of transglutaminase(TGase), caused a significant decrease of the ratio of NCC-Spd / NCC-Put, CC-Put contents, respectively, in concert with the marked decreases of ATPase activity, —SH group content and its tolerance to osmotic stress. All the results above suggested that osmotic stress tolerance of wheat seedlings was associated with the ATPase activity, the contents of —SH group, NCC-Spd and CC-Put in mitochondrial membrane.

Double-layered osmotic pump controlled release tablets of actarit: In vitro and in vivo evaluation

The aim of the study was to develop actarit double-layered osmotic pump tablets to overcome the weak points of actarit common tablets, such as short half-life and large plasma concentration fluctuations. Single factor experiment and orthogonal test were applied to optimize the formulation;the pharmacokinetic study was performed in beagle dogs adopting actarit common tablets as reference tablets. The optimal formulation was as follows: drug layer: 150 mg actarit, 240 mg PEO-N80, 50 mg NaCl;push layer: 140 mg PEO-WSR303, 20 mg NaCl;coating solution: 30 g cellulose acetate and 6 g PEG 4000 in 1000 ml 94% acetone solution, 60 mg coating weight gain. The pharmacokinetic study showed that T max was prolonged by the contrast of commercial common tablets with constant drug release rate, but the bioavailability was equivalent. And a good in vivo –in vitro correlation of the actarit osmotic pump tablets was also established. The designed actarit osmotic pump tablets can be applied for rheumatoid arthritis, proposing a promising replacement for the marked common products.

Effect of Salinity on Hemolymph Osmotic Pressure,Sodium Concentration and Na^+-K^+-ATPase Activity of Gill of Chinese Crab,Eriocheir sinensis

The effects of salinity on hemolymph osmotic pressure, Na+ concentration and Na+-K+-ATPase activity of gill of Chinese crab Eriocheir sinensis were studied. The results showed that hemolymph osmotic pressure and Na+ concentration increased signifi- cantly (P<0.05), and the Na+-K+-ATPase activity of gills decreased significantly (P<0.05) when salinity increased from 0 to 16. The hemolymph osmotic pressure and Na+ concentration in each treatment group rose remarkably at 0.125 d or 0.25 d, while the Na+-K+-ATPase activity of gill reduced gradually with increased experiment time in 3 d. Then the three parameters remained at a constant level after 0.25 d, 0.125 d and 3 d, respectively, and higher hemolymph osmotic pressure, higher Na+ concentration and lower Na+-K+-ATPase activity of gill occurred at higher salinity. The effect of salinity change on protein concentration of hemolymph was indistinct (P>0.05); However, the protein concentration decreased gradually with the increase of salinity from 0.25 d to 1 d, and then tended to be stable from day 1 to day 15.

Effects of osmotic stress on antioxidant enzymes activities in leaf discs of P_(SAG12)-IPT modified gerbera

Leaf senescence is often caused by water deficit and the chimeric gene PSA612-1PT is an auto-regulated gene delaying leaf senescence. Using in vitro leaf discs culture system, the changes of contents of chlorophylls, carotenoids, soluble protein and thiobarbituric acid reactive substance （TBARS） and antioxidant enzymes activities were investigated during leaf senescence of PSA612-1PT modified gerbera induced by osmotic stress compared with the control plant （wild type）. Leaf discs were incubated in 20%, 40% （w/v） polyethylene glycol （PEG） 6 000 nutrient solution for 20 h under continuous light [ 130 μmol/（m^2·s）]. The results showed that the contents of chlorophylls, carotenoids and soluble protein were decreased by osmotic stress with the decrease being more pronounced at 40% PEG, but that, at the same PEG concentration the decrease in the transgenic plants was significantly lower than that in the control plant. The activities of superoxide dismutase （SOD）, catalases （CAT）, ascorbate peroxidase （APX）, guaiacol peroxidase （GPX） and dehydroascorbate reductase （DHAR） were stimulated by PEG treatment. However, the increases were higher in PSA612-IPT transgenic plants than in the control plants, particularly at 40% PEG treatment. Lipid peroxidation （TBARS content） was increased by PEG treatment with the increase being much lower in transgenic plant than in the control plant. It could be concluded that the increases in the activities ofantioxidant enzymes including SOD, CAT, APX, GPX and DHAR were responsible for the delay of leaf senescence induced by osmotic stress.

Can semipermeable membranes coating materials influence in vivo performance for paliperidone tri-layer ascending release osmotic pump tablet:In vitro evaluation and in vivo pharmacokinetics study

One purpose of this study was to develop a paliperidone(PAL)tri-layer ascending release pushepull osmotic pump(TA-PPOP)tablet which could meet the needs of clinical applications.And another purpose was to investigate whether different coating materials influenced in vivo performance of TA-PPOP.The ascending release mechanism of this trilayer delivery system on theory was elaborated.TA-PPOP was prepared by means of coating with cellulose acetate(CA)or ethyl cellulose(EC).Several important influence factors such as different core tablet compositions and different coating solution ingredients involved in the formulation procedure were investigated.The optimization of formulation and process was conducted by comparing different in vitro release behaviors of PAL.In vitro dissolution studies indicated that both the two formulations of different coating materials were able to deliver PAL at an ascending release rate during the whole 24 h test.The in vivo pharmacokinetics study showed that both self-made PPOP tablets with different coating had a good in vitro-in vivo correlation(IVIVC)and were bioequivalent with the brand product,which demonstrated no significant influence of the coating materials on the in vivo release acceleration of TA-PPOP.

Interactive effect of shade and PEG-induced osmotic stress on physiological responses of soybean seedlings

Intensively farmed crops used to experience numerous environmental stresses.Among these,shade and drought significantly influence the morpho-physiological and biochemical attributes of plants.However,the interactive effect of shade and drought on the growth and development of soybean under dense cropping systems has not been reported yet.This study investigated the interactive effect of PEG-induced osmotic stress and shade on soybean seedlings.The soybean cultivar viz.,C-103 was subjected to PEG-induced osmotic stress from polyethylene glycol 6000(PEG-6000)under shading and non-shading conditions.PEG-induced osmotic stress significantly reduced the relative water contents,morphological parameters,carbohydrates and chlorophyll contents under both light environments.A significant increase was observed in osmoprotectants,reactive oxygen species and antioxidant enzymes in soybean seedlings.Henceforth,the findings revealed that,seedlings grown under non-shading conditions produced more malondialdehyde and hydrogen peroxide contents as compared to the shade-treated plants when subjected to PEG-induced osmotic stress.Likewise,the shaded plants accumulated more sugars and proline than non-shaded ones under drought stress.Moreover,it was found that nonshaded grown plants were more sensitive to PEG-induced osmotic stress than those exposed to shading conditions,which suggested that shade could boost the protective mechanisms against osmotic stress or at least would not exaggerate the adverse effects of PEG-induced osmotic stress in soybean seedlings.

A time-released osmotic pump fabricated by compression-coated method: Formulation screen, mechanism research and pharmacokinetic study

In this investigation,time-released monolithic osmotic pump(TMOP)tablets containing diltiazem hydrochloride(DIL)were prepared on the basis of osmotic pumping mechanism.The developed dosage forms were coated by Kollidon®SR-Polyethylene Glycol(PEG)mixtures via compression-coated technology instead of spray-coating method to form the outer membrane.For more efficient formulation screening,a three-factor five-level central composite design(CCD)was introduced to explore the optimal TMOP formulation during the experiments.The in vitro tests showed that the optimized formulation of DIL-loaded TMOP had a lag time of 4 h and a following 20-h drug release at an approximate zero-order rate.Moreover,the releasemechanismwas proven based on osmotic pressure and its profile could be well simulated by a dynamic equation.After oral administration by beagle dogs,the comparison of parameters with the TMOP tablets and reference preparations show no significant differences for C_(max)(111.56±20.42,128.38±29.46 ng/ml)and AUC_(0-48 h)(1654.97±283.77,1625.10±313.58 ng h/ml)but show significant differences for T_(max)(13.00±1.16,4.00±0.82 h).These pharmacokinetic parameters were consistent with the dissolution tests that the TMOP tablets had turned out to prolong the lag time of DIL release.