• <tr id="yyy80"></tr>
  • <sup id="yyy80"></sup>
  • <tfoot id="yyy80"><noscript id="yyy80"></noscript></tfoot>
  • 99热精品在线国产_美女午夜性视频免费_国产精品国产高清国产av_av欧美777_自拍偷自拍亚洲精品老妇_亚洲熟女精品中文字幕_www日本黄色视频网_国产精品野战在线观看 ?

    Validation and application of Vierordt’s spectrophotometric method for simultaneous estimation of tamoxifen/coenzyme Q10 in their binary mixture and pharmaceutical dosage forms

    2017-01-19 06:26:08
    關(guān)鍵詞:胡人馬刺北國(guó)

    Department of Pharmaceutics,Faculty of Pharmacy,Helwan University,Ain-Helwan 11790,Cairo,Egypt

    Validation and application of Vierordt’s spectrophotometric method for simultaneous estimation of tamoxifen/coenzyme Q10 in their binary mixture and pharmaceutical dosage forms

    Eman S.El-Leithy*,Rania S.Abdel-Rashid

    Department of Pharmaceutics,Faculty of Pharmacy,Helwan University,Ain-Helwan 11790,Cairo,Egypt

    A R T I C L EI N F O

    Article history:

    Available online 11 February 2016

    Tamoxifen citrate

    Coenzyme Q10

    Binary mixture

    Solid lipid nanoparticles

    Validation

    For the sake of improving patient compliance and sustainability of chemotherapy healthcare system,both TC and CoQ10 were formulated as solid lipid nanoparticles(SLNs).The study was focused on establishing and validating a simple and reproducible spectrophotometric method for simultaneous determination of TC and CoQ10 in their binary mixture or pharmaceutical dosage forms.A new method based on simultaneous estimation of drug mixture without prior separation was developed.Validation parameters were checked with International Conference on Harmonization(ICH)guidelines.The accuracy and reproducibility of proposed method was statistically compared to HPLC.The TC and CoQ10 were quantifed at absorptivity wavelengths of 236 nm and 275 nm,respectively.Calibration curves obeyed Beer’s law in range of 2–14 μg/ml with a correlation coeffcient(R2)of 0.999 in both methanol and simplifed simulated intestinal fuid(SSIF).The%means recovery of TC and CoQ10 in pure state or binary mixture at various concentration levels were all around 100%. The low values of SD and%RSD(<2%)confrm high precision and accuracy of the proposed method.Formulated SLNs showed different%means recovery in range 81–92%for TC and 32–59%for CoQ10.The data obtained by applying simultaneous Vierordt’s equations showed no statistical signifcance in comparison to HPLC.Vierordt’s method was successfully applied as a simple,accurate,precise,and economical analysis method for estimating TC and CoQ10 concentrations in pure state,binary mixture and pharmaceutical dosage forms.

    ?2016 Production and hosting by Elsevier B.V.on behalf of Shenyang Pharmaceutical University.This is an open access article under the CC BY-NC-ND license(http:// creativecommons.org/licenses/by-nc-nd/4.0/).

    1.Introduction

    Imbalance between antioxidants and reactive oxygen species (ROS)results in oxidative stress,leading to cellular damage. The ROS plays a major role in causing mitochondrial changes linked to cancer and metastasis[1,2].

    Tamoxifen citrate(TC)is an important non-steroidal estrogen antagonist drug that adheres to all stages of estrogen receptor positive breast cancer treatment as well as longterm prophylactic therapy in high-risk and post-menopausal women[3].However,uptake of antioxidants by tissue to reduce ROS production could be instrumental in controlling cancer[4]. Coenzyme Q10(CoQ10)is a proven potent antioxidant and protective agent against many diseases including cancer[5].It was recorded that prescribing vitamins(C and E),essential fatty acids,and CoQ10 for those patients receiving TC allows for cancer enhancing treatment outcomes and improves chemotherapy tolerability[6].

    For the sake of improving patients’compliance with long term medication and sustainability of healthcare system,we were interested in formulating a new drug delivery system loaded with both drugs.Simple and fast simultaneous estimation of drug concentrations in their mixture or therapeutic delivery systems is posing a real challenge to formulators.Recently,many estimation techniques were developed on raw overlapping spectral data to enable mixture resolution,such as different order derivatives[7–9],derivatives of the ratio spectrum[10,11]and ratio subtraction technique[12].Valuable researches were published based on using simultaneous equation(Vierordt’s method)for estimation of 2 or more drugs in combined mixtures or pharmaceutical dosage forms[13–16].

    Extensive literature survey revealed that no spectrophotometric method is available for simultaneous determination of TC/CoQ10 mixture.Despite the numerous advantages of HPLC for simultaneous determination of different drug mixture,most offcial methods suffered from well-established drawbacks such as:high solvent cost,low resolution power columns,long run time,diffcult selection of column packing materials,use of the gradient elution,limited choice of detectors,base-line drift on varying the eluent,lower signal-to-noise and signal-tobackground ratios and increased instrument complexity[17]. Additionally,chemical and physical properties ofTC and CoQ10 revealed very big difference in their polarity and partition coeffcients[18,19].Hence,the current study was focused on establishing and validation of Vierordt’s method for spectrophotometric determination of TC and CoQ10 concentrations in their binary mixture or pharmaceutical dosage forms.The accuracy and precision of the proposed method were confrmed by HPLC measurement.Student’s paired t-test was applied to compare the values of%means drug recovery by the two analytical methods.

    2.Materials and methods

    2.1.Materials

    Tamoxifen citrate(m.wt:563.62)was generously given as a gift by Medical United Pharmaceutical Company,Cairo,Egypt. CoenzymeQ10(m.wt:863.34)and lecithin were given as gifts from Amriya Company for Pharmaceutical Industries,Rushdie, Alexandria,Egypt.Labrafac(capryl/caprylic triglycerides)was kindly donated by Gattefosse Company,France.Stearic acid, sodium lauryl sulfate(SLS),methanol,sodium dihydrogen phosphate(NaH2PO4),isopropyl alcohol,Tween 20,sodium chloride(NaCl)and sodium hydroxide(NaOH)were purchased from EL-Gomhoria Company,Cairo,Egypt.The n-hexane and triethylamine were also obtained from Sharlu(Spain) and Sigma Aldrich(Germany),respectively.All other chemicals were of analytical grade.Distilled water was used throughout the study.

    2.2.Equipment

    Mechanical stirrer(IKAWorks,Asia Sdn.Bhd.,Malaysia),cooling centrifuge(Hermle Z 200A,Germany),hot plate stirrer(Jenway 1000,U.K)and analytical balance(Setra BL-410S,U.S)were used. A JASCO V-530 double beam UV-VIS spectrophotometer with a fxed slit width(2 nm)connected to a computer loaded with spectra manager program was applied for spectral acquisition and elaboration of the data obtained.Quartz cuvettes,1-cm path length were used for measuring the light absorption in ultra-violet region(200–400 nm).Shimadzu HPLC model 20A auto sampler(Japan),UV detector and quaternary pump system with auto-gasser were used for HPLC separation and estimation of drug concentrations.

    2.3.Methods

    Both TC and CoQ10 are poorly soluble drugs(Fig.1A and B). Methanol and simplifed simulated intestinal fuid(SSIF)were chosen as dissolution media to ensure complete solubility of both drugs.The SSIF was prepared according to Taupitz et al. [20].Blank SSIF(pH 6.5)was prepared by dissolving 3.438 g NaH2PO4 and 6.186 g of NaCl in 900 ml of distilled water.The pH was adjusted with 0.1 N NaOH solution.The SSIF was reached by adding 0.25%w/v SLS and Tween 20.The volume was adjusted to 1000 ml by isopropyl alcohol.The buffer solution was ultrasonicated for 15 min then stirred for another15 min.

    2.3.1.Preparation of sample solutions of drugs mixture

    Alcoholic sample solution ofTC and CoQ10 binary mixture was prepared at lab-ratio of 5:5.A 0.5 ml of standard working solutions(100 μg/ml)of each drug was transferred to 10 ml volumetric fask and the volume was completed to the mark with methanol to obtain sample solution of 5 μg/ml concentration for each drug.The same procedure was followed with SSIF at strength ratio 10:10 to get sample solution of 10 μg/ml for each drug.

    2.3.2.Preparation of TC/CoQ10 loaded solid lipid nanoparticles

    In order to validate the developed simultaneous equations for estimating TC and CoQ10 concentrations in a pharmaceutical dosage form,solid lipid nanoparticles(SLNs)were chosen as a novel drug delivery system[21].The SLNs offer unique properties such as small size,large surface area,and high drug loading[22].The SLNs were prepared by micro-emulsifcationfollowed by ultrasonication technique(Fang et al.)[23].Stearic acid(2%,w/v)was melted at 60–70°C.Accurate weights of CoQ10 and TC were dispersed in lipid melt to have homogenous drug–lipid mixture.Lipid melt was added to aqueous surfactant solution(3%,w/v P188)preheated 10°C above the melting point of the lipid.Emulsifcation process was done under stirring by a high-speed mechanical stirrer at 6000 rpm for 10 min.Finally,the formed crude emulsion was ultrasonicated using a probe for 10 minutes to prevent crystallization of lipids and minimize particle size.The obtained nanoemulsion was cooled to room temperature to allow formation of SLNs dispersion.Separation of SLNs was carried out by centrifugation at 17,000 rpm for 30 min.The supernatant was discarded and sediment was washed with cold distilled water with repeating centrifugation process.A mixture of stearic acid with lecithin or labrafac was applied for preparing other formulae of SLNs following the previous procedures.A specifed weight of each formula was dissolved in methanol for subsequent determination of drug concentrations in a pharmaceutical dosage form[24].

    Fig.1–Chemical structure of(A)tamoxifen citrate and(B)coenzyme Q10.

    2.3.3.Development and validation of simultaneous spectrophotometric method for estimating TC and CoQ10 concentrations in pure state,binary mixture and SLNs

    Firstly,working solutions of both drugs in pure state were scanned separately in UV range 200–400 nm against blanks for determining maximum wavelengths(λmax).The λmaxwere 236 nm and 275 nm for TC and CoQ10,respectively(Fig.2). Vierordt’s spectrophotometric method applied for simultaneous estimation of drugs that have measurable absorbance at λmaxof each other[25].For preparing calibration curves,serial solutions(2–14 μg/ml)of each drug were prepared using their working solutions.The absorbance was measured in triplicate at λmax236 and 275 nm.For linearity studies,calibration curves for TC and CoQ10 were plotted.Values of molar absorptivity of both drugs were determined by reconstructing the calibration curves using drugs molar concentrations.The regression equations,molar absorptivity and optical parameters are presented in Table 1.

    Two simultaneous equations for determining drug concentrations in their mixture were developed using their molar absorptivity coeffcient values(Eqs.1 and 2).

    where CTCand CCoQ10are concentrations of TC and CoQ10,respectively,in their sample solution(mole/L).A1and A2are absorbances of laboratory prepared mixtures at 236 nm and 275 nm,respectively.The α1and α2are molar absorptivities of TC at 236 nm and 275 nm,respectively.However,β1and β2are molar absorptivities of CoQ10 at 236 nm and 275 nm,respectively.All validation procedures were performed in accordance with International Conference on Harmonization ICH Q2(R1) guideline[26].To validate Vierordt’s formula on the working solutions of TC and CoQ10,the%means recovery(±SD)and %relative standard deviations(%RSD)at two concentration levels for each drug(8 and 12 μg/ml)in their pure state were calculated.Precision of the developed method was also ascertained by repeatability and intermediate precision studies.The in intraday study(repeatability)of the proposed method was performed with a minimum of three replicate measurements.The concentrations of the two drugs were calculated every two hours (0,2,and 4 h).In inter-day(intermediate precision)study, the concentrations of drugs were calculated on threeconsecutive days.The results of data statistical analysis are given in Table 2.Limit of Detection(LOD)and Limit of Quantifcation(LOQ)were also calculated.The LOD is the lowest amount of analyte,which can be detected but not necessarily quantitated as an exact value(Eq.3).The LOQ is the lowest amount of analyte,which can be quantitatively determined with suitable precision and accuracy(Eq.4).

    Fig.2–Overlay spectrum of tamoxifen citrate and coenzyme Q10 mixture wavelength scan.

    Table 1–Linearity regression equations and molar absorptivity values for TC and CoQ10 calibration curves at chosen wavelengths in different dissolution media.

    where‘σ’is the standard deviation of the response and‘S’is the slope of the calibration curve.The results of LOD and LOQ for TC and CoQ10 are shown in Table 2.

    Secondly,developedVierordt’s simultaneous equations(Eqs. 1 and 2)were applied for determining TC and CoQ10 concentrations in their lab mixtures of methanol and SSIF and SLNs. Parameters of accuracy and precision were also determined to validate developed simultaneous equations used for determining the concentrations of drugs in their binary mixture or pharmaceutical dosage forms(Tables 3,4;respectively).

    2.3.4.HPLC as a reference method for determining drug concentrations

    The content of TC and CoQ10(pure state or SLNs)was determined by HPLC as confrmatory reference test for evaluating the developedVierordt’s spectrophotometric method for direct estimation of drug concentrations without prior separation. Reference analysis method was performed by Shimadzu chromatographic system where reverse phase column C18 phenomax 150 mm×4.6 mm,with a porosity 5×10?3mm,was used as a stationary phase.The logP for both drugs was reported to be 6.3 and 17.16,whereas polar surface area was 145 and 52.6 for TC and CoQ10,respectively[18,19].This vast difference in physicochemical properties was expected to make chromatographic separation of TC and CoQ10 from their mixture by one elution system in short retention time with maximum recovery,precision and repeatability very hard or nearly impossible.Hence two mobile phases with different natures were chosen,a polar mobile phase for separation ofTC and a non-polar mobile phase for separation of CoQ10.A mixture of tri-ethylamine acetate buffer:methanol with a ratio of 24.3:75.7 v/v was found to be optimal forTC separation[27].Methanol:n-hexane with a ratio of 65:35 v/v was used for CoQ10 separation[28].The injection volume was 50 μl with fow rate 1.5 ml/min and UV detection of both drugs was carried out at 275 nm(Figs.3 and 4).

    Accurately weighed 10 mg of TC or CoQ10 were transferred to 100 ml volumetric fasks(stock solutions).Both drugs were dissolved in 25 ml methanol,and volume was made up to mark with suitable mobile phase.Serial dilutions were made in concentration range of 2–14 μg/ml for each drug.Values obtained were used to build calibration models and to assess predictive capacity of models.Recovery studies wereperformed on a couple of concentrations of 8 and 12 μg/ml.The %recovery(±SD)and%relative standard deviations(%RSD)were calculated(Table 5).

    Table 2–Validation sheet for determination of TC and CoQ10 in their pure forms,by applying Vierordt’s spectrophotometric method.

    HPLC method was also applied for determining drug content in samples of SLNs.Weighted 50 mg of SLNs was dissolved in each mobile phase and injected into HPLC column to estimate the amount ofTC or CoQ10 loaded in SLNs.The accuracy and precision were also performed(Table 6).

    Table 3–Validation sheet for determination of TC and CoQ10 in their binary mixture at different dissolution media,by applying Vierordt’s spectrophotometric method.

    2.3.5.Statistical analysis

    All data were expressed as mean(±SD).Data were analyzed using the program SPSS 16.0(SPSS Inc.,Chicago,IL,USA)with help of paired samplesT where P<0.05 was conducted as signifcance level.

    3.Results and discussion

    3.1.Linearity

    Calibration curves of TC and CoQ10 at 236 nm and 275 nm in methanol and SSIF media showed high linearity.The correlation between sample concentrations and their absorbencies complied with Beer’s law as illustrated by high values ofregression coeffcients(R2≈0.999)and small values of intercepts(Table 1).

    Table 4–Validation sheet for determination of TC and CoQ10 in their SLNs dosage form,by applying Vierordt’s spectrophotometric method.

    Table 5–Recovery studies by HPLC method for pure drugs.

    Table 6–Results of HPLC method for estimating of drugs content in SLNs.

    3.2.Development of Vierordt’s equations for simultaneous estimation of TC and CoQ10

    The spectral overlapping between spectral graphs of TC and CoQ10(Fig.2)was suffcient to demonstrate that direct spectrophotometric measurements cannot be applied for simultaneous determination of the two drugs in their mixture without prior separation.Two simultaneous equations for calculatingTC and CoQ10 concentrations in their binary mixture were developed using molar absorptivity coeffcient values.The developed equations in methanol and SSIF for each drug were given:

    In methanol:

    where A1and A2are the absorbance value at 236 and 275 nm, respectively,and C is the concentration in mole/l.Once absorptivity values are determined,very little time is required for calculating drug concentrations using the absorbances of samples at two selected wavelengths.Employing simultaneous equation is a very simple method and can be employed for a routine analysis of TC and CoQ10.

    3.3.Validation of Vierordt’s simultaneous equations

    3.3.1.For drugs in pure state

    The accuracy of an analytical method is the closeness of test results to that of true values[29].In order to ensure reliability of proposed method,accuracy was confrmed by recovery studies at two concentration levels(8 and 12 μg/ml).The %means recovery ofTC and CoQ10 were 98.54–100.14 and 99.69–101.32,respectively,indicating the accuracy of the method (Table 2).The low values of SD and%RSD(<2%)are another confrmatory parameters for high precision,reproducibility and accuracy of proposed method(Table 2).The%RSD forTC at the two concentration levels was between 0.829–0.987 and 1.547–1.55 in methanol and SSIF,respectively.Moreover,%RSD at 8 μg/ ml was 1 and 0.682 for CoQ10 in methanol and SSIF,respectively, and was 0.379 and 1.269 at concentration level of 12 μg/ml in methanol and SSIF,respectively.

    Precision study was also established by measuring absorbance of sample solution without changing the assay procedure at different time intervals.It is clearly obvious that the proposed method was highly precise,due to high%recovery presented in Table 2(100.03–102%for intra-day and 98.46–102.4%for inter-day measurements).The LOD was 0.088 μg/ ml and 0.043 μg/,while LOQ was 0.26 μg/ml and 0.142 μg/ml for TC in methanol and SSIF,respectively.The LOD for CoQ10 was 0.16 μg/ml and 0.1 μg/ml,whereas LOQ was 0.16 μg/ml and 0.3 μg/ml in methanol and SSIF,respectively(Table 2).

    3.3.2.For drugs in lab mixtures

    The developed method was also successfully applied for determination of TC and CoQ10 in their binary mixture solution at different ratio strengths.In methanol,the concentration ratio 5:5 μg/ml,showed%means recovery 98.4%±0.32 for TC and 101.2%±0.21%for CoQ10.Meanwhile,99.9%±0.63%and 100.3%±0.39%were%means recovery for TC and CoQ10,respectively,in SSIF at concentration ratio 10:10 μg/ml.Both%RSD and%error were less than 2%,indicating high accuracy of the developed method.The results also ensured high repeatability and intermediate precision(Table 3).

    3.3.3.For drugs loaded in SLNs

    The SLNs were prepared loaded with 10 mg of each drug.The %means recovery of each drug was determined by applying the developed equations.The results showed high agreement with the loaded amount of drugs(estimated%means recovery was 81–92%forTC and 32–59%for CoQ10).The SD,%RSD and%error were less than 2,confrming the method’s accuracy(Table 4). The developed method for simultaneous estimation ofTC and CoQ10 loaded in SLNs was valid,applicable,and with high repeatability and intermediate precision.

    馬刺押送秀容月明回北國(guó),途中并不安穩(wěn),百姓“歡迎”秀容月明自不必說(shuō),還有人暗殺秀容月明,這些人,全是寧人,還有胡人被買(mǎi)通了,要秀容月明的命。

    Fig.3–Representative HPLC chromatogram of TC using triethylamine acetate buffer:methanol(24.3:75.7,v/v)mobile phase.

    3.4.HPLC as a reference method

    In HPLC method,an adequate separation of eluted compounds was optimized.Several aliquots of standard solutions ofTC and CoQ10 at 2–14 μg/ml range were prepared with mobile phases.The optimum wavelength for detection of both drugs was 275 nm.The peak shapes of both drugs were symmetrical(Fig.3 and 4).The average retention times forTC and CoQ10 were found to be and 3.2 and 2.6 min,respectively.Constructed calibration curves showed high linearly with R2≈0.999. Application of HPLC method for pure drugs showed perfect recovery values(99.66–101.4%)for both drugs with high precision (%RSD<2)(Table 5).Results of HPLC%means recovery from different formulae of SLNs were presented in Table 6.The method was accurate and precise as indicated by recovery studies and%RSD not more than 2%.

    Recorded values of%drug recovery from the two analytical methods were statistically analyzed using student paired t-test(Table 7).There were no signifcant differences between %drug recovery by the developedVierordt’s method and HPLC method(P<0.05,at 95%level of signifcance).Vierordt’s spectrophotometric method revealed high degree of accuracy for estimating TC and CoQ10 in their binary mixture and pharmaceutical dosage forms.

    4.Conclusion

    Fig.4–Representative HPLC chromatogram of CoQ10 using methanol:n-hexane(65:35,v/v)mobile phase.

    Table 7–Statistical analysis of%drug means recovery of Vierordt’s and HPLC methods.

    Admitting that HPLC method is expensive in hardware and chromatographic reagents,simultaneous estimation of two drugs with different polarity are yet more complex and moreexpensive.Vierordt’s method was successfully applied for selective routine analysis ofTC and CoQ10 concentrations in their binary mixture or pharmaceutical dosage forms without prior separation.The developed method was validated according to per ICH(Q2R1)guidelines.Recovery studies were satisfactory with low SD,%RSD,high repeatability and intermediate precision.Statistical analysis of data revealed no signifcant differences between drug concentrations estimated byVierordt’s method and those obtained by HPLC,confrming accuracy and precision of the developed method.Vierordt’s method has the benefts of being simple,rapid,direct,economic,with minimum data manipulation and not requiring sophisticated techniques or instruments.

    Acknowledgments

    The authors are thankful to Mona N.Sweilam(Analytical Chemistry Department,Faculty of Pharmacy,Helwan University)for providing guidance and technical support required for this research.

    R E F E R E N C E S

    [2]Klaunig J,Kamendilus LM.The role of stress in carcinogenesis.Annu Rev Pharmacol Toxicol 2004;44:239–267.

    [3]MacGregor J,Jordan V.Basic guide to the mechanisms of antiestrogen action.Pharmacol Rev 1998;50:151–196.

    [4]Perumal SS,Shanthi P,Sachdanandam P.Augmented effcacy of tamoxifen in rat breast tumorigenesis when gavaged along with ribofavin,niacin,and CoQ10:effects on lipid peroxidation and antioxidants in mitochondria.Chem Biol Interact 2005;152:49–58.

    [5]Muta-Takada K,Terada T,Yamanishi H,et al.Coenzyme Q10 protects against oxidative stress-induced cell death and enhances the synthesis of basement membrane components in dermal and epidermal cells.Biofactors 2009;35:435–441.

    [6]Lockwood K,Moesgaard S,Hanioka T,et al.Apparent partial remission of breast cancer in‘high risk’patients supplemented with nutritional antioxidants,essential fatty acids and coenzyme Q10.Mol Aspects Med 1994;(Suppl. 15):231–240.

    [7]Altinos S,Tekeli D.Analysis of glimepiride by using derivative UV spectrophotometric method.J Pharm Biomed Anal 2001;24:507–515.

    [8]Lemus Gallego JM,Perez Arroyo J.Simultaneous resolution of dexamethasone and polymyxin b by spectrophotometry derivative and multivariate methods.Anal Lett 2001;34:1265–1283.

    [9]Nanda RK,Pangarkar VB,Thomas AB,et al.Simultaneous estimation of montelukast sodium and bambuterol hydrochloride in tablets by spectrophotometry.Hindustan Antibiot Bull 2008;49–50:29–33.

    [10]Darwish HW,Hassan SA,Salem MY,et al.Three different spectrophotometric methods manipulating ratio spectra for determination of binary mixture of amlodipine and atorvastatin.Spectrochim Acta 2011;83:140–148.

    [11]Hassib ST,El-Zaher AA,Fouad MA.Validated stabilityindicating derivative and derivative ratio methods for the determination of some drugs used to alleviate respiratory tract disorders and their degradation products.Drug Test Anal 2011;3:306–318.

    [12]El-Bardicy MG,Lotfy HM,El-Sayed MA,et al.Smart stabilityindicating spectrophotometric methods for determination of binary mixtures without prior separation.JAOAC Int 2008;91:299–310.

    [13]Giriraj P,Sivakkumar T.New simple spectrophotometric method for the simultaneous estimation of paracetamol and fupirtine maleate in pure and pharmaceutical dosage form. Int J Spectro 2014;1–7.

    [14]Visagaperumal D,Vasavi A.Development and validation of UV spectrophotometric method(Vierordt’s Method)for simultaneous estimation of eperisone hydrochloride and paracetamol in tablets.Ph Tech Med 2014;3:441–444.

    [15]Rizk MS,Merey HA,Tawakkol SM,et al.Applicability of bivariate calibration algorithm and Vierordt method for simultaneous determination of timolol maleate and brimonidine tartrate in their binary mixture and pharmaceutical dosage form.IJPSR 2014;5:2631–2641.

    [16]Sandeep S,Marina K.Spectrophotometric quantitative estimation of atenolol and losartan potassium in bulk drugs and pharmaceutical dosage form.WJPPS 2014;3:1026–1033.

    [17]Michael WD.The essence of modern HPLC:advantages, limitations,fundamentals,and opportunities.LCGC 2013;31:472–479.

    [18]US EPA,Estimation program interface(EPI)Suite,Nov 13, 2006.

    [19]Teeranachaideekul V,Souto EB,Junyaprasert VB,et al. Encapsulation of ascorbyl palmitate in nanostructured lipid carriers NLC–effects of formulation parameters on physicochemical stability.Int J Pharm 2007;340:198–206.

    [20]Taupitz T,Klein S.Can biorelevant media be simplifed by using SLS and Tween 80 to replace bile compounds?Todd J 2010;4:30–37.

    [21]Garud A,Singh D,Garud N.Solid lipid nanoparticles(SLN): method,characterization and applications.Int Curr Pharm J 2012;1:384–393.

    [22]Loxley A.Solid lipid nanoparticles for the delivery of pharmaceutical actives.Drug Del Techno 2009;9:20.

    [23]Fang JU,Fang CL,Liu CH,et al.Lipid nanoparticles as vehicles for topical psoralen delivery:solid lipid nanoparticles(SLN)versus nanostructured lipid carriers (NLC).Eur J Pharm Biopharm 2008;70:633–640.

    [24]Yuan H,Wang LL,Du YZ,et al.Preparation and characteristics of nanostructured lipid carriers for controlreleasing progesterone by melt-emulsifcation.Colloids Surf B Biointerfaces 2007;60:174–179.

    [25]Beckett AH,Stenlake JB.Practical pharmaceutical chemistry. 4th ed.New Delhi:CBS Publishers and Distributors;1997.p. 282–307.

    [26]ICH Harmonized Tripartite Guideline,Validation of analytical procedures:text and methodology,Q2(R1),current step 4 version,parent guidelines on methodology;November 2005.

    [27]Monteagudo E,Gándola L,González Y,et al.Development, characterization,and in vitro evaluation of tamoxifen microemulsions.J Drug Del 2012;1–11.

    [28]Karpin′ska J,Miko?uc′B,Motkowski R,et al.HPLC method for simultaneous determination of retinol,alpha-tocopherol and coenzyme Q10 in human plasma.J Pharm Biomed Anal 2006;18:232–236.

    [29]Shrikrishna B,Vinod P,Patil RN,et al.Validation of simple and rapid UV-spectrophotometric method with stress degradation study for sildenafl citrate.Res J Pharm Tech 2012;5:214–218.

    *< class="emphasis_italic">Corresponding author.

    .Department of Pharmaceutics and Industrial Pharmacy,Faculty of Pharmacy,Helwan,University,Ain Helwan, POB 11795,Cairo,Egypt.Tel.:+201147162722;fax:+2025541601.

    E-mail address:emansaddar@hotmail.com(E.S.El-Leithy).

    Peer review under responsibility of Shenyang Pharmaceutical University.

    http://dx.doi.org/10.1016/j.ajps.2016.02.005

    1818-0876/?2016 Production and hosting by Elsevier B.V.on behalf of Shenyang Pharmaceutical University.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).

    猜你喜歡
    胡人馬刺北國(guó)
    靈渠胡人俑與貢道的外國(guó)使臣
    文史春秋(2022年5期)2022-07-18 08:41:56
    破山劍
    江南如今到北國(guó)
    黃河之聲(2020年11期)2020-07-16 13:26:54
    白樺生北國(guó)
    文苑(2019年20期)2019-11-20 02:12:33
    白樺生北國(guó)
    北國(guó)紅豆
    談?wù)勌仆醭适抑械暮孙L(fēng)俗
    儒釋道思想的融合體 胡人騎羊青瓷插座
    大眾考古(2015年12期)2015-06-26 08:53:16
    最偉大的馬刺
    NBA特刊(2014年7期)2014-04-29 00:44:03
    久久精品国产自在天天线| 日韩免费高清中文字幕av| 一本色道久久久久久精品综合| 99久久中文字幕三级久久日本| 99热国产这里只有精品6| 少妇被粗大猛烈的视频| 亚洲av成人精品一二三区| 亚洲av男天堂| 国产精品人妻久久久影院| 六月丁香七月| 亚洲国产成人一精品久久久| 亚洲在久久综合| 永久免费av网站大全| 丰满人妻一区二区三区视频av| 热re99久久国产66热| 超碰97精品在线观看| 欧美变态另类bdsm刘玥| 三级国产精品欧美在线观看| 2018国产大陆天天弄谢| 曰老女人黄片| 午夜影院在线不卡| 午夜福利在线观看免费完整高清在| 精品一区二区免费观看| 一级毛片我不卡| 99热这里只有精品一区| 人人妻人人澡人人爽人人夜夜| 观看av在线不卡| 9色porny在线观看| 如何舔出高潮| 久久女婷五月综合色啪小说| 精品一区二区免费观看| 一本一本综合久久| 精品久久久噜噜| 大陆偷拍与自拍| 国产伦精品一区二区三区视频9| 一区二区三区四区激情视频| 亚洲精品乱码久久久v下载方式| 久久鲁丝午夜福利片| 少妇人妻一区二区三区视频| 91久久精品国产一区二区成人| 丝袜在线中文字幕| 久久鲁丝午夜福利片| av免费观看日本| 视频中文字幕在线观看| 久久久久久人妻| 人妻制服诱惑在线中文字幕| 成人国产麻豆网| 久久97久久精品| 如何舔出高潮| 99精国产麻豆久久婷婷| 日韩中文字幕视频在线看片| 国产成人aa在线观看| 亚洲丝袜综合中文字幕| 日韩av不卡免费在线播放| 日韩av免费高清视频| 男人爽女人下面视频在线观看| 精品久久久噜噜| 寂寞人妻少妇视频99o| 日韩大片免费观看网站| 下体分泌物呈黄色| 秋霞伦理黄片| 男人舔奶头视频| 一级毛片电影观看| 99热这里只有是精品在线观看| 久久久欧美国产精品| 永久免费av网站大全| 26uuu在线亚洲综合色| 搡老乐熟女国产| 午夜91福利影院| 亚洲欧美一区二区三区国产| 日韩 亚洲 欧美在线| 国产欧美日韩一区二区三区在线 | 国产亚洲精品久久久com| 国产淫片久久久久久久久| 妹子高潮喷水视频| 欧美精品高潮呻吟av久久| 亚洲国产精品999| 你懂的网址亚洲精品在线观看| 汤姆久久久久久久影院中文字幕| 亚洲欧美成人综合另类久久久| 欧美精品国产亚洲| 日日爽夜夜爽网站| 成年人午夜在线观看视频| 亚洲三级黄色毛片| 亚洲精品亚洲一区二区| 97在线视频观看| 亚洲av免费高清在线观看| 亚洲av成人精品一区久久| 亚洲欧美一区二区三区黑人 | 赤兔流量卡办理| 亚洲精品乱码久久久久久按摩| av一本久久久久| 在现免费观看毛片| 香蕉精品网在线| 欧美老熟妇乱子伦牲交| 美女脱内裤让男人舔精品视频| 亚洲精品aⅴ在线观看| 国产成人精品无人区| 欧美日韩精品成人综合77777| 免费观看性生交大片5| 欧美成人精品欧美一级黄| 少妇高潮的动态图| 91午夜精品亚洲一区二区三区| 2018国产大陆天天弄谢| 国产成人aa在线观看| 日日啪夜夜爽| 婷婷色av中文字幕| 午夜久久久在线观看| 综合色丁香网| 一级毛片我不卡| 欧美丝袜亚洲另类| 又爽又黄a免费视频| 亚洲无线观看免费| 寂寞人妻少妇视频99o| 亚洲欧美精品专区久久| 欧美精品国产亚洲| 午夜老司机福利剧场| 下体分泌物呈黄色| 午夜精品国产一区二区电影| 欧美一级a爱片免费观看看| 国产成人精品福利久久| 日本免费在线观看一区| 22中文网久久字幕| 亚洲伊人久久精品综合| 精品卡一卡二卡四卡免费| 国产一区有黄有色的免费视频| 边亲边吃奶的免费视频| 91在线精品国自产拍蜜月| 亚洲精品国产av蜜桃| 欧美日韩一区二区视频在线观看视频在线| 中国三级夫妇交换| 亚洲av.av天堂| 欧美最新免费一区二区三区| 自拍偷自拍亚洲精品老妇| 国产一区亚洲一区在线观看| 国产精品欧美亚洲77777| 99九九线精品视频在线观看视频| 国内精品宾馆在线| 女的被弄到高潮叫床怎么办| 另类亚洲欧美激情| 夫妻性生交免费视频一级片| 亚洲精品,欧美精品| 国产欧美另类精品又又久久亚洲欧美| 亚洲精品久久午夜乱码| 日韩亚洲欧美综合| 高清毛片免费看| 人人妻人人爽人人添夜夜欢视频 | av福利片在线| 国产亚洲91精品色在线| 精品卡一卡二卡四卡免费| 黄色欧美视频在线观看| 亚洲精品久久久久久婷婷小说| 久久久久久久精品精品| 久久精品熟女亚洲av麻豆精品| 国产精品国产三级专区第一集| 天堂8中文在线网| 久久人人爽人人片av| 亚洲精品乱码久久久v下载方式| 亚洲性久久影院| 日本-黄色视频高清免费观看| 深夜a级毛片| 免费久久久久久久精品成人欧美视频 | 高清av免费在线| 王馨瑶露胸无遮挡在线观看| 秋霞在线观看毛片| 一个人免费看片子| 国产成人精品福利久久| 欧美亚洲 丝袜 人妻 在线| 亚洲精品色激情综合| 免费观看无遮挡的男女| 久久久久久久亚洲中文字幕| 久久国产乱子免费精品| 一级毛片我不卡| 国产成人午夜福利电影在线观看| 国产一区二区三区av在线| 国产精品久久久久久av不卡| 尾随美女入室| 五月玫瑰六月丁香| 久久久久久久国产电影| 国产极品天堂在线| 午夜福利影视在线免费观看| 国产在线视频一区二区| 丰满乱子伦码专区| 精品亚洲成a人片在线观看| 日韩人妻高清精品专区| 久久午夜福利片| 日韩一区二区视频免费看| av福利片在线| 人妻少妇偷人精品九色| 夫妻性生交免费视频一级片| 色视频在线一区二区三区| 久久久国产欧美日韩av| 观看av在线不卡| 99久国产av精品国产电影| 国产精品人妻久久久久久| 国产伦精品一区二区三区视频9| 国产成人aa在线观看| 精品酒店卫生间| 亚州av有码| 丰满饥渴人妻一区二区三| 国产高清不卡午夜福利| 观看美女的网站| 老熟女久久久| 如日韩欧美国产精品一区二区三区 | 国产男女内射视频| 久久精品国产亚洲av天美| 久久国产精品大桥未久av | 久久久久久久久久久免费av| 中国美白少妇内射xxxbb| 我的老师免费观看完整版| 搡女人真爽免费视频火全软件| 国产综合精华液| 婷婷色综合www| 亚洲av在线观看美女高潮| 国产探花极品一区二区| 日本免费在线观看一区| 亚洲国产欧美在线一区| 国模一区二区三区四区视频| 日本91视频免费播放| 久久久久久久久久久久大奶| 亚洲怡红院男人天堂| 精品卡一卡二卡四卡免费| 婷婷色av中文字幕| 久久av网站| 国内少妇人妻偷人精品xxx网站| av天堂中文字幕网| 国产成人精品久久久久久| 久久久久久伊人网av| 精品一区二区三区视频在线| 国产av精品麻豆| 9色porny在线观看| 国产av一区二区精品久久| 2022亚洲国产成人精品| 日韩精品有码人妻一区| 麻豆成人av视频| 人体艺术视频欧美日本| 国产黄色免费在线视频| 自拍欧美九色日韩亚洲蝌蚪91 | av黄色大香蕉| 国产男女超爽视频在线观看| 最新的欧美精品一区二区| 欧美亚洲 丝袜 人妻 在线| 国产精品三级大全| 国产 精品1| 久久久久久人妻| 男人添女人高潮全过程视频| 性高湖久久久久久久久免费观看| .国产精品久久| 免费播放大片免费观看视频在线观看| 国产黄色视频一区二区在线观看| 亚洲第一区二区三区不卡| 天堂8中文在线网| 美女中出高潮动态图| 国产 一区精品| 国产淫片久久久久久久久| 亚洲中文av在线| 一边亲一边摸免费视频| 亚洲精品一区蜜桃| 国产黄频视频在线观看| 男人爽女人下面视频在线观看| 少妇高潮的动态图| 亚洲精品国产成人久久av| 精品人妻一区二区三区麻豆| 人人妻人人澡人人看| 国产视频内射| 亚洲精品日韩在线中文字幕| 一本久久精品| 波野结衣二区三区在线| 久久青草综合色| 少妇的逼水好多| 日日撸夜夜添| 精品亚洲乱码少妇综合久久| 日韩中字成人| 建设人人有责人人尽责人人享有的| 制服丝袜香蕉在线| 一区二区三区四区激情视频| 国产午夜精品一二区理论片| 2018国产大陆天天弄谢| 国产成人精品一,二区| 久久久久精品久久久久真实原创| 亚洲精品中文字幕在线视频 | 男男h啪啪无遮挡| 成人午夜精彩视频在线观看| 有码 亚洲区| 亚洲精品一区蜜桃| 国内少妇人妻偷人精品xxx网站| 亚洲精品国产成人久久av| 三上悠亚av全集在线观看 | 免费观看的影片在线观看| 成年女人在线观看亚洲视频| 免费观看av网站的网址| 日韩中文字幕视频在线看片| 亚洲精品第二区| 久久av网站| 亚洲av男天堂| 最近的中文字幕免费完整| av视频免费观看在线观看| 一区二区三区精品91| 精品一区在线观看国产| 嘟嘟电影网在线观看| 一级毛片黄色毛片免费观看视频| 久久久久精品久久久久真实原创| 日韩欧美精品免费久久| 国产精品人妻久久久久久| 精华霜和精华液先用哪个| 亚洲va在线va天堂va国产| 80岁老熟妇乱子伦牲交| 国内少妇人妻偷人精品xxx网站| 99久久综合免费| 国产伦精品一区二区三区四那| 精品久久久久久久久亚洲| 国内精品宾馆在线| 国产探花极品一区二区| 一本色道久久久久久精品综合| 少妇 在线观看| 看十八女毛片水多多多| 一本—道久久a久久精品蜜桃钙片| 老司机亚洲免费影院| 人人妻人人爽人人添夜夜欢视频 | 亚洲婷婷狠狠爱综合网| 欧美 日韩 精品 国产| 成人免费观看视频高清| 精品久久久久久久久亚洲| 在线观看免费高清a一片| 丝袜在线中文字幕| 黑丝袜美女国产一区| av又黄又爽大尺度在线免费看| 国产片特级美女逼逼视频| 蜜桃在线观看..| 日本av免费视频播放| 精品少妇内射三级| 一级爰片在线观看| 久久免费观看电影| 一级二级三级毛片免费看| 国产一级毛片在线| 精品国产露脸久久av麻豆| 啦啦啦在线观看免费高清www| 久久人人爽人人片av| 少妇高潮的动态图| www.色视频.com| 日韩 亚洲 欧美在线| 日本黄色日本黄色录像| 自拍欧美九色日韩亚洲蝌蚪91 | 九九久久精品国产亚洲av麻豆| 国产精品99久久99久久久不卡 | 色哟哟·www| 欧美一级a爱片免费观看看| 十分钟在线观看高清视频www | 精华霜和精华液先用哪个| 久久精品久久久久久久性| 欧美亚洲 丝袜 人妻 在线| 99热6这里只有精品| 边亲边吃奶的免费视频| 亚洲国产色片| 亚洲激情五月婷婷啪啪| a级毛色黄片| 日韩av在线免费看完整版不卡| 亚洲国产精品成人久久小说| 永久免费av网站大全| 国产老妇伦熟女老妇高清| 日本黄大片高清| 热99国产精品久久久久久7| 成年美女黄网站色视频大全免费 | 夜夜爽夜夜爽视频| 国产亚洲91精品色在线| a级一级毛片免费在线观看| 国产亚洲午夜精品一区二区久久| 午夜免费男女啪啪视频观看| 成人18禁高潮啪啪吃奶动态图 | 亚洲图色成人| 亚洲av.av天堂| 嘟嘟电影网在线观看| 国产成人精品无人区| 国产国拍精品亚洲av在线观看| 亚洲精品国产av成人精品| 国产成人精品一,二区| 深夜a级毛片| 丰满少妇做爰视频| 赤兔流量卡办理| 99久久精品热视频| 色婷婷久久久亚洲欧美| 亚洲国产精品999| 亚洲国产av新网站| 人妻少妇偷人精品九色| 精品少妇黑人巨大在线播放| 观看av在线不卡| 97精品久久久久久久久久精品| 久久久久久久久久人人人人人人| 伦理电影免费视频| 热re99久久精品国产66热6| 在线播放无遮挡| 久久久久久久久大av| 人妻系列 视频| 色网站视频免费| 丰满乱子伦码专区| 人人妻人人爽人人添夜夜欢视频 | 美女中出高潮动态图| 有码 亚洲区| 国产精品国产av在线观看| 噜噜噜噜噜久久久久久91| 又爽又黄a免费视频| 亚洲av国产av综合av卡| 18禁在线播放成人免费| 久久久久久人妻| 日韩人妻高清精品专区| 91精品伊人久久大香线蕉| 秋霞伦理黄片| www.色视频.com| 日本黄色片子视频| 精品国产一区二区三区久久久樱花| 精品午夜福利在线看| 久久久久国产精品人妻一区二区| 亚洲av二区三区四区| 成人漫画全彩无遮挡| 十八禁高潮呻吟视频 | 91在线精品国自产拍蜜月| 久久久国产欧美日韩av| 亚洲精品亚洲一区二区| 国产免费一区二区三区四区乱码| 亚洲国产精品999| www.色视频.com| 免费黄色在线免费观看| 国产伦在线观看视频一区| 最黄视频免费看| 久久久久网色| 亚洲在久久综合| 亚洲欧洲精品一区二区精品久久久 | 久久av网站| 黑人高潮一二区| 丝袜在线中文字幕| 亚洲精品自拍成人| av国产久精品久网站免费入址| 国产精品人妻久久久久久| 亚洲精品色激情综合| 内地一区二区视频在线| freevideosex欧美| 在线观看免费高清a一片| 晚上一个人看的免费电影| 人体艺术视频欧美日本| 久久久国产一区二区| 乱人伦中国视频| 久久99精品国语久久久| 99久国产av精品国产电影| 国产成人精品福利久久| 亚洲情色 制服丝袜| 中文字幕久久专区| 欧美日韩精品成人综合77777| 国产片特级美女逼逼视频| 欧美日本中文国产一区发布| 黑人高潮一二区| 国产精品伦人一区二区| 中文天堂在线官网| 国产精品久久久久成人av| 99久久精品一区二区三区| 国产精品蜜桃在线观看| 亚洲精品中文字幕在线视频 | 99热国产这里只有精品6| 免费在线观看成人毛片| 卡戴珊不雅视频在线播放| 亚洲精品亚洲一区二区| 精品99又大又爽又粗少妇毛片| 如日韩欧美国产精品一区二区三区 | 丰满迷人的少妇在线观看| 亚洲av不卡在线观看| 精品久久久久久电影网| 秋霞伦理黄片| av在线播放精品| 久久久久久久久久久免费av| 久久久久网色| 国产精品无大码| 99热这里只有精品一区| 久久人人爽人人爽人人片va| 国产精品99久久久久久久久| videossex国产| 欧美精品人与动牲交sv欧美| 欧美3d第一页| 成人国产av品久久久| 亚洲国产日韩一区二区| 一本大道久久a久久精品| 亚洲激情五月婷婷啪啪| 狠狠精品人妻久久久久久综合| 亚州av有码| 在线播放无遮挡| 国产精品久久久久久av不卡| 欧美精品一区二区大全| 晚上一个人看的免费电影| 最近最新中文字幕免费大全7| 国产av一区二区精品久久| 啦啦啦中文免费视频观看日本| 美女脱内裤让男人舔精品视频| 最近2019中文字幕mv第一页| 国产极品粉嫩免费观看在线 | 伦精品一区二区三区| 国产免费一区二区三区四区乱码| a级毛片在线看网站| 亚洲av综合色区一区| 少妇人妻久久综合中文| 日韩一区二区视频免费看| 久久青草综合色| 精品熟女少妇av免费看| 性色av一级| 国产伦精品一区二区三区视频9| 日韩精品免费视频一区二区三区 | 久久久久精品久久久久真实原创| 男人添女人高潮全过程视频| 免费观看性生交大片5| 插逼视频在线观看| 国产中年淑女户外野战色| 搡女人真爽免费视频火全软件| 日韩电影二区| 久久久久久久精品精品| 亚洲国产精品一区二区三区在线| 热re99久久精品国产66热6| 亚洲av.av天堂| 97超碰精品成人国产| 王馨瑶露胸无遮挡在线观看| 久久免费观看电影| 亚洲图色成人| 狂野欧美激情性xxxx在线观看| 国产精品一区二区三区四区免费观看| 麻豆成人午夜福利视频| 精品国产乱码久久久久久小说| 男人添女人高潮全过程视频| 久久97久久精品| 国产女主播在线喷水免费视频网站| 香蕉精品网在线| 欧美精品国产亚洲| 免费大片黄手机在线观看| 国产精品久久久久成人av| 国产黄频视频在线观看| 欧美精品高潮呻吟av久久| 国产精品一区二区在线不卡| 插逼视频在线观看| 国产69精品久久久久777片| 丰满人妻一区二区三区视频av| 中国美白少妇内射xxxbb| 午夜福利影视在线免费观看| 黄片无遮挡物在线观看| 在线观看一区二区三区激情| 国产黄片视频在线免费观看| 日本黄大片高清| 欧美 日韩 精品 国产| 久久人人爽人人爽人人片va| 大香蕉久久网| 精品人妻熟女av久视频| 最新中文字幕久久久久| 少妇被粗大的猛进出69影院 | 成人国产av品久久久| 久久人人爽av亚洲精品天堂| 久久亚洲国产成人精品v| 天美传媒精品一区二区| 五月开心婷婷网| 王馨瑶露胸无遮挡在线观看| 肉色欧美久久久久久久蜜桃| 日韩亚洲欧美综合| 亚洲精品视频女| 婷婷色av中文字幕| 视频区图区小说| 国产亚洲av片在线观看秒播厂| 久久久久人妻精品一区果冻| 一级毛片黄色毛片免费观看视频| 婷婷色av中文字幕| 2018国产大陆天天弄谢| 日日摸夜夜添夜夜添av毛片| 天美传媒精品一区二区| 精品国产露脸久久av麻豆| 色视频www国产| 亚洲一级一片aⅴ在线观看| 日韩精品免费视频一区二区三区 | 亚洲精品久久久久久婷婷小说| 伊人久久国产一区二区| 一级毛片久久久久久久久女| 天堂中文最新版在线下载| 欧美日韩亚洲高清精品| 色哟哟·www| 亚洲成人av在线免费| 天堂俺去俺来也www色官网| 各种免费的搞黄视频| 免费看光身美女| 日韩 亚洲 欧美在线| 一级毛片 在线播放| 精品人妻熟女毛片av久久网站| 亚洲国产色片| 亚洲国产av新网站| 日日摸夜夜添夜夜添av毛片| 国产av国产精品国产| 色5月婷婷丁香| 久久久午夜欧美精品| 色视频www国产| 久久精品国产自在天天线| 欧美成人午夜免费资源| 九九久久精品国产亚洲av麻豆| 又黄又爽又刺激的免费视频.| 狂野欧美激情性xxxx在线观看| 日韩熟女老妇一区二区性免费视频| 日韩免费高清中文字幕av| 在线观看av片永久免费下载| 国产精品久久久久久精品古装| 日本wwww免费看| 美女中出高潮动态图| 偷拍熟女少妇极品色| 久久女婷五月综合色啪小说| 男人爽女人下面视频在线观看| 日韩制服骚丝袜av| 欧美激情国产日韩精品一区| 国产精品99久久99久久久不卡 | 欧美少妇被猛烈插入视频| 免费看光身美女| 一本久久精品| a级毛片在线看网站| 久久精品国产亚洲网站| 少妇丰满av| 免费少妇av软件| 精品一区在线观看国产| 一个人看视频在线观看www免费|