PART 1 Kev Npaj Thiab Kev Ntsuas Ntawm Microemulsion-based Transdermal Delivery Of Cistanche Tubulosa Phenylethanoid Glycosides
Mar 06, 2022
Hu rau: Audrey Hu Whatsapp / hp: 0086 13880143964 Email:audrey.hu@wecistanche.com
JIANHUA YANG1*, HUANHUAN XU1-3*, & et al.
Abstract.
Lub hom phiaj tseem ceeb ntawm txoj kev tshawb no yog los tsim ib qho tshiab microemulsion (ME) formulation kom xaphenylethanoid glycoside los ntawm cistanche(PG) siv rau hauv daim tawv nqaij lighteners thiab tshuaj pleev thaiv hnub. Cov roj theem tau raug xaiv los ntawm cov tshuaj solubility, thaum cov surfactant thiab cosurfactant raug tshuaj xyuas thiab xaiv los ntawm lawv lub peev xwm solubilizing thiab qhov ua tau zoo uas lawv tsim MEs. Pseudo ternary phase diagrams tau tsim los ntsuas ME cheeb tsam thiab tsib cov qauv ntawm cov roj-hauv-dej MEs raug xaiv ua tsheb. Nyob rau hauv vitro daim tawv nqaij permeation thwmsim tau ua kom optimize ME formulation thiab soj ntsuam nws permeability piv rau cov saline tov. Lub physicochemical zog ntawm optimized ME thiab permeating peev xwm ntawm PG(phenylethanoid glycoside los ntawm cistanche) xa los ntawm ME no kuj tau tshawb xyuas. Kev ua kom zoo rau ME yog tsim los ntawm isopropyl myristate (7 feem pua, w/w), Cremorphor EL (21 feem pua, w/w), propylene glycol (7 feem pua, w/w) thiab dej (65 feem pua, w/w). Tus nqi ntawm PG(phenylethanoid glycoside los ntawm cistanche) uas permeated los ntawm excised nas daim tawv nqaij thaum nqa los ntawm ME yog ~ 1.68 lub sij hawm uas thaum PG nqa los ntawm saline tov xwb. Qhov sib npaug ntawm PG hauv microemulsion (4149.650± 37.3 µg·cm-2 ) tau ntau dua li ntawm PG hauv cov kua ntsev (2288.63±20.9 µg· cm -2 ). Tsis tas li ntawd, lub permeability coefficient qhia tau hais tias optimized microemulsion yog ib tug ntau npaum cov cab kuj rau transdermal xa ntawm PG dua li cov kev tswj (8.87±0.49 cm/hx{16}} vs. 5.41±0.12 cm/hx{21}} ). Ua ke, lub peev xwm permeating ntawm ME-carried PG tau nce ntau dua piv nrog cov kua ntsev.
Taw qhia
Herba cistanche,tshuaj ntsuab tonic feem ntau muab faib rau thaj tsam suab puam, tau nquag siv hauv tshuaj suav tshuaj. Txog niaj hnub no, ntau qhov kev tshawb fawb tau ua los tshawb xyuas nws cov khoom siv tshuaj biopharmaceutical, suav nrog kev txhim kho kev nco, kev sib deev potency, dawb radical scavenging, thiab kev tiv thaiv kev laus (1). Qhov tseem ceeb ntawm H. cistanche yogPhenylethanoid glycoside (PG). Cov kev tshawb fawb yav dhau los tau qhia tias PG inhibits kev ua haujlwm ntawm tyrosinase, tus nqi txwv enzyme rau kev sib txuas ntawm melanin hauv tib neeg lub cev (2). Tsis tas li ntawd, PG(phenylethanoid glycoside los ntawm cistanche) tau raug tshaj tawm tias yog lub luag haujlwm rau kev khawb ntawm 2, 2-diphenyl-1-picrylhydrazyl radicals (3), thiab tiv thaiv keratinocytes los ntawm ultraviolet (UV) hluav taws xob. Yog li ntawd, cov khoom no yuav muaj peev xwm nyob rau hauv daim tawv nqaij depigmentation. Tshuaj pleev ib ce tau nquag siv nyob rau hauv cov tshuaj pleev ib ce, nrog rau cov tshuaj xa ncaj qha mus rau lub cev nto (4). Microemulsions (ME) yog ib tug tshiab tshuaj xa system conventionally tsim ntawm roj, surfactant, cosurfactant thiab aqueous theem (5) thiab tau raug tshaj tawm los txhim kho tus nqi thiab nqus lipophilic tshuaj (6). Tsis tas li ntawd, vim nws txaus siab solubility, tsis tshua muaj tawv nqaij khaus thiab permeability siab, nws yuav tsum tau siv nyob rau hauv cov tshuaj pleev (7,8). Rau qhov zoo tshaj plaws ntawm peb txoj kev paub, ob peb txoj kev tshawb fawb tau ua qhov twg PG tau xa los ntawm cov tshuaj pleev xim siv microemulsion. Nyob rau hauv txoj kev tshawb no, ib tug roj-hauv-dej (O / W) nanoemulsion xa system rau transdermal tswj tau tsim, thiab PG tau muab tso rau hauv nanoemulsion (9,10). Lub caij no, kev npaj thiab ua tus cwj pwm ntawm PG-raws li nanoemulsion tau ua los ntawm kev tshawb xyuas qhov transdermal tso tawm hauv vitro.
Cov ntaub ntawv thiab cov txheej txheem Reagents.
Cremorphor EL thiab isopropyl myristate (IPM) tau yuav los ntawm Sigma Aldrich; Merck Millipore (Darmstadt, Lub teb chaws Yelemees). Ethanol, oleic acid (OA), thiab Tween -80 tau yuav los ntawm Guangcheng Chemical Reagent Co., Ltd. (Tianjin, Suav). Ethyl oleate tau yuav los ntawm Shanghai Chemical Reagent Co., Ltd. (Shanghai, Suav). Tag nrho cov tshuaj thiab cov kuab tshuaj siv tau yog qib analytical reagent. Kev npaj thiab kev ntsuam xyuas ntawm micro emulsion-based transdermal xa ntawm Cistanche tubulosa phenylethanoid glycosides JIANHUA YANG1*, HUAN HUAN XU1-3*, SHANSHAN WU2, BOWIE JU2, DANDAN ZHU2, YAO YAN2 {MEI 9) } Department of Pharmacy, Thawj Tsev Kho Mob; 2 Department of Natural Medicines, College of Pharmacy, Xinjiang Medical University, Urumqi, Xinjiang 830011; 3 Department of Pharmacy, Kanghua Tsev Kho Mob, Dongguan, Guangdong 523003, PR Tuam Tshoj Tau Txais Lub Kaum Ob Hlis 2, 2015; Tau txais Lub Kaum Ib Hlis 29, 2016, DOI: 10.3892/MMR.2017.6147 Kev xa mus rau: Dr. Junping Hu, Department of Natural Medicines, College of Pharmacy, Xinjiang Medical University, 393 Xinyi Road, Urumqi, Xinjiang 8300155mail: PR Tuam Tshoj @yeah.net * Pab txhawb nqa sib npaug Keywords: phenylethanoid glycoside, microemulsion, transdermal delivery, skin lightener, sunscreen yang et al: ME-BASED PG FOR COSMETIC APPLICATION 1110 Preparation of PhGs. PhG(phenylethanoid glycoside los ntawm cistanche) tau npaj raws li niaj hnub piav (11).
Cua qhuavC. tubulosatau powered thiab rho tawm los ntawm percolation nrog 80 feem pua EtOH. Lub percolate tau evaporated nyob rau hauv lub siab, tom qab ntawd los ntawm kev pom ntawm cov kua residual. Cov filtrate tau concentrated thiab chromatographed ntawm SP-825 macroporous resin kem siv 0, 30, 50, 70, thiab 90 feem pua EtOH hauv dej li eluants. Cov 30-50 feem pua EtOH eluants tau concentrated thiab qhuav kom tau PhG nplua nuj feem. UV spectrophotometric qhia cov ntsiab lus ntawm PhG(phenylethanoid glycoside los ntawm cistanche) yog 87.6% . Kev tshuaj ntsuam cov roj, surfactants, thiab cosurfactants rau ME. Solubility ntsuam xyuas tau ua los xaiv cov khoom tsim nyog rau kev npaj ntawm ME formulation nrog lub peev xwm loj thauj khoom. Hauv cov txheej txheem no, ntau tshaj PG tau ntxiv rau hauv 4 ml ntawm txhua qhov ntawm cov tshuaj nram qab no: IPM, kua paraffin, OA, Cremophor EL, Tween-80, absolute ethanol, propylene glycol, glycerin, thiab PEG400. , raws. Tom qab ntawd, qhov sib xyaw ua ke tau shaken reciprocally ntawm 37˚C rau 72 teev, tom qab ntawd centrifugation ntawm 12,830 xg rau 10 min. Tom qab ntawd, cov pellet tau rov muab tso rau hauv methanol, thiab PG tau txiav txim siab siv UV spectrophotometric ntawm 333 nm. Tsim nyog diluted daws cov roj, surfactants thiab cosolvents nyob rau hauv methanol tau txais kev pab raws li ib tug dawb paug tswj. Kev tsim kho ntawm cov duab kos duab. Txhawm rau kom tau txais qhov sib txawv ntawm cov khoom siv rau thaj tsam microemulsion uas twb muaj lawm, pseudo ternary theem daim duab tau tsim los siv txoj kev titration dej raws li tau piav qhia yav dhau los (12). Daim duab peb-theem tau npaj nrog 1: 3, 1: 1, thiab 3: 1 qhov hnyav piv ntawm surfactant rau cosurfactant. Cov roj theem thiab cov surfactant sib tov ces sib tov ntawm qhov hnyav piv ntawm 1: 9, 2: 8, 3: 7, 4: 6, 5: 5, 6: 4, 7: 3, 8: 2 thiab 9: 1 . Cov roj thiab cov tshuaj surfactant sib tov sib xyaw ua ke thiab tau diluted dropwise nrog dej huv hauv qab sib nqus nplawm (300 rpm) ntawm chav tsev kub kom txog thaum pob tshab ME tau txais. Qhov concentration ntawm cov khoom tau raug kaw kom ua tiav daim duab pseudo ternary theem. Raws li cov duab kos, qhov tsim nyog cov ntaub ntawv raug xaiv rau kev npaj ntawm PG-raws li ME. Kev npaj ntawm ME thiab cov tshuaj aqueous ntawm PG. Tag nrho ntawm 5 MEs (ME1-5) raug xaiv raws li cov duab kos duab nrog cov surfactant: Cosurfactant hnyav piv ntawm 3: 1 (Table I). Microemulsion systems tau npaj los ntawm kev sib xyaw roj nrog cov sib tov ntawm surfactant thiab cosurfactant, thiab dej tau ntxiv meej rau hauv cov roj theem nrog sib nqus nplawm (300 r / min) ntawm 37˚C. Cov tshuab tau sib npaug siv cov sib nqus sib nqus rau 30 feeb ua raws li kev ua kom tiav qhov tsim nyog ntawm PG raws li ultrasonication. Cov tshuaj aqueous tau npaj nrog tib cov ntsiab lus PG yaj hauv dej huv. Cov yam ntxwv ntawm microemulsion. Qhov nruab nrab me me thiab polydispersity Performance index ntawm MEs tau soj ntsuam los ntawm photon correlation spectroscopy (Malvern Instruments, Ltd., Malvern, UK). Tag nrho cov qauv tau diluted nrog dej ntawm 1: 5 piv thiab tau lim los ntawm 0.22 µm lim. Qhov ntsuas tau ua nyob rau hauv lub thermostatic chamber ntawm 25˚C hauv triplicate. Lub morphology ntawm PG microemulsions tau soj ntsuam siv kev xa hluav taws xob hluav taws xob (JEM-100CXII; JEOL Ltd., Tokyo, Nyiv). Luv luv, ib qho poob ntawm cov qauv diluted tau muab tso rau ntawm daim phiaj zaj duab xis-coated tooj liab, tom qab ntawd staining nrog ib tee ntawm 2 feem pua phosphotungstic acid aqueous tov.
Qhov nruab nrab txoj kab uas hla ntawm microemulsions tau txiav txim siab los ntawm photon correlation spectroscopy instrument (BI{{0}}SM; Brookhaven Instruments Corporation, Holtsville, NY, USA) ntawm chav tsev kub. Lub viscosity ntawm ME tsheb tau ntsuas ntawm 25˚C, siv NDJ-8S digital viscometer (Shanghai Precision thiab Scientific Instrument Co., Ltd., Shanghai, Tuam Tshoj) nrog rau qhov tsis muaj. 1 rotor teeb ntawm 6 0 rpm. kev txiav txim siab pH. Tus nqi pH ntawm MEs tau txiav txim siab ntawm 25˚C siv Phs-3C digital acidimeter (Shanghai REX Instruments Factory, Shanghai, Suav). Qhov ntsuas qhov ntsuas qhov ntsuas kub tau ntsuas nrog lub ntsuas kub ntawm Abbe refractometer (Optical Instrument Factory, Shanghai, Suav). Kev npaj ntawm daim tawv nqaij. Txiv neej Kunming nas hnyav 20 g tau yuav los ntawm Kev Tshawb Fawb Tsiaj Center ntawm Xinjiang Medical University (Xinjiang, Suav). 10 nas (6 lub lis piam) tau txais kev yoo mov rau 1 lub lis piam ntawm 12 teev lub teeb / 12 teev tsaus ntuj, ntawm chav sov (24 ± 2˚C), nrog cov av noo ntawm 50 ± 15 feem pua. Txhua tus tsiaj tau txais kev noj zaub mov zoo thiab dej. Cov plaub hau raug tshem tawm nrog ib qho hluav taws xob clipper. Tom qab lub davhlau ya nyob twg tshuaj loog nrog chloral hydrate (10 feem pua) ntawm kev txhaj tshuaj subcutaneous, cov ntaub so ntswg ntawm daim tawv nqaij raug tshem tawm ntawm thaj tsam plab thiab cov rog subcutaneous thiab cov ntaub so ntswg raug tshem tawm. Cov ntaub so ntswg tau muab tso rau hauv lub tub yees ntawm 4˚C thaum hmo ntuj. Cov txheej txheem kev tshawb fawb tau pom zoo los ntawm Pawg Neeg Saib Xyuas Kev Ncaj Ncees ntawm Xinjiang Medical University (Xinjiang, Tuam Tshoj). Kev tshawb nrhiav hauv vitro permeation. Kev sim permeation tau ua raws li tau piav qhia dhau los (12). Cov tawv nqaij excised tau clamped ntawm tus pub thiab lub receptor chamber ntawm ib ntsug diffusion cell nrog ib tug zoo diffusion cheeb tsam ntawm 2.8 cm2. Lub receptor chamber tau ntim nrog tshiab, ib txwm saline. Lub diffusion cell tau khaws cia ntawm 37˚C siv lub recirculating dej da dej thiab cov tshuaj nyob rau hauv lub receptor chambers yog stirred tsis tu ncua ntawm 200 rpm. Tom qab qhov no, qhov kev sim tshuaj (1.0 ml) tau maj mam muab tso rau hauv chav pub dawb. Tom qab ntawd, 3 ml ntawm cov tshuaj nyob rau hauv lub receptor chamber raug tshem tawm thiab hloov nrog ib tug sib npaug zos ntim ntawm tshiab saline nyob rau hauv lub sij hawm predetermined (0, 2, 4, 6, 8, 10 thiab 24 h). Cov qauv tau txais los ntawm receptor chamber tau siv los txiav txim PG(phenylethanoid glycoside los ntawm cistanche)qib siv UV spectroscopy ntawm lub wavelength ntawm 333 nm. Qhov sib ntxiv ntawm PG uas permeated los ntawm excised nas daim tawv nqaij raug xam raws li cov qauv hauv qab no:
Qhov twg Qn yog cov nyiaj tau los ntawm lub sijhawm muab t, Cn yog cov tshuaj concentration ntawm cov tshuaj tau txais kev daws teeb meem ntawm txhua lub sijhawm kuaj, Ci yog cov tshuaj concentration ntawm cov qauv, S yog thaj chaw muaj txiaj ntsig zoo (S{{0}) }}.8 cm2 ), thiab V0 thiab Vi yog cov ntim ntawm cov tshuaj txais thiab cov qauv, feem. Tus nqi nce (Qn) ntawm PG(phenylethanoid glycoside los ntawm cistanche)permeated tau npaj raws li lub sijhawm ua haujlwm (t) rau txhua qhov kev tsim. Tus nqi permeation ntawm PG ntawm lub xeev khov kho (Jss, µg / cm-2 / h-1 ) los ntawm cov tawv nqaij nas raug xam los ntawm txoj kab nqes ntawm txoj kab nqes ntawm cov phiaj xwm ntawm Qnversus lub sijhawm. Lub permeability coefficient (Kp, cm / h) raug xam raws li cov qauv hauv qab no:
Qhov twg Kp yog tus permeability coefficient, Jss yog cov efflux xam nyob rau hauv tsis tu ncua-lub xeev, thiab C0 sawv cev rau cov tshuaj concentration uas nyob twj ywm nyob rau hauv lub tsheb. Kev tshawb nrhiav tawv nqaij. Cov ntu hauv qab no piav qhia txog kev sib piv ntawm ex vivo permeation tus cwj pwm, tus nqi sib sau, tus nqi permeation, permeability coefficient thiab tawv tuav cov yam ntxwv ntawm optimized ME formulations (PG cov ntsiab lus, 2 feem pua, w / w) thiab cov tshuaj aqueous. Thaum kawg ntawm qhov kev sim permeation, cov tshuaj seem nyob hauv daim tawv nqaij tau txiav txim siab siv homogenization. Tom qab ntxuav nrog ib txwm saline, daim tawv nqaij raug txiav mus rau hauv me me thiab muab tso rau hauv ib lub iav raj uas muaj 3 ml methanol nyob rau hauv ib da dej dej khov. Cov qauv yog homogenized nrog ceev ntawm 12000 r/min. rpm rau 2 min, thiab ces centrifuged ntawm 12,830 xg kab rov tav rau 30 min ntawm 25˚C. Lub supernatant tau dhau los ntawm cov lim microporous (0.45 µm), thiab PG(phenylethanoid glycoside los ntawm cistanche)Cov qib hauv cov supernatant tau txiav txim siab los ntawm UV spectroscopy ntawm lub wavelength ntawm 333 nm. Kev kawm ruaj khov. Lub cev ruaj khov ntawm PG-loaded ME tau tshawb xyuas los ntawm qhov pom tseeb, qhov ntsuas qhov loj me thiab kev sib cais theem, uas tau pom ntawm 2-8˚C thiab nyob rau hauv chav tsev kub rau 3 lub hlis. Centrifugation tau ua ntawm 12,830 xg rau 30 min ntawm 25˚C txhawm rau ntsuas lub cev ruaj khov ntawm ME. Kev sib cais theem thiab qhov concentration ntawm PG tau tshawb xyuas txhua hli los txiav txim qhov ntsuas kub zoo. Kev ruaj ntseg tshuaj raug soj ntsuam ntawm cov tshuaj-loaded formulations, khaws cia ntawm 2-8˚C thiab nyob rau hauv chav tsev kub, nrog rau PG cov ntsiab lus txiav txim los ntawm UV spectrophotometric ntawm 333 nm. Kev kuaj tawv nqaij rhiab heev. Kev ntsuam xyuas ntawm daim tawv nqaij rhiab heev tau ua rau luav (qhov hnyav 2.02.5 kg) los ntsuas qhov ua rau khaus khaus ntawm daim ntawv thov ntawm cov qauv tsim raws li tau piav qhia dhau los (13). Cuaj Holland luav (16 lub lis piam; hnyav 2. Cov tsiaj tau txais kev yoo mov rau 1 lub lis piam ntawm 12 teev lub teeb / 12 teev tsaus ntuj, ntawm chav sov (24 ± 2˚C), nrog cov av noo ntawm 50 ± 15 feem pua. Txhua tus tsiaj tau txais kev noj zaub mov zoo thiab dej. Cua embolism tau siv rau kev txi. Cov txheej txheem siv nyob rau hauv txoj kev tshawb no tau pom zoo los ntawm Pawg Neeg Saib Xyuas Kev Ncaj Ncees ntawm Xinjiang Medical University (Xinjiang, Suav). Cov plaub hau nyob tom qab raug tshem tawm ~ 24 teev ua ntej kev tswj hwm ntawm ME formulations. Tsiaj txhu tau muab faib ua pawg hauv qab no: Ib pawg ME optimized (n=3), nrog rau cov thawj coj ntawm optimized ME muaj 2 feem pua (w/w) PG; ib pawg PG saline (n{33}}), nrog rau cov tshuaj pleev ib ce ntawm cov kua ntsev uas muaj 2 feem pua (w/w) PG; thiab tswj cov pab pawg saline (n=3), raws li kev tswj hwm cov tshuaj saline ib txwm. Kev tswj hwm tau ua ob zaug ib hnub rau 5 hnub. Cov tsiaj tau pom tias muaj cov tsos mob ntawm khaus lossis hloov ntawm daim tawv nqaij, suav nrog erythema, papule, flakiness thiab dryness (14). Tom qab tshem tawm cov tshuaj, kev soj ntsuam rau ib leeg lossis ntau qhov kev tswj hwm tau txuas ntxiv rau 3 hnub. Cov qhab nia khaus ntawm qhov chaw kuaj tau raug soj ntsuam los ntawm kev txiav txim siab txog qhov ntawm erythema thiab edema raws li cov hauv qab no: 1, tsis pom cov tshuaj tiv thaiv; 2, me ntsis tshuaj tiv thaiv; 3, cov tshuaj tiv thaiv nruab nrab thiab 4, cov tshuaj tiv thaiv hnyav (15,16). Thaum kawg, tag nrho cov qhab nia khaus khaus rau txhua tus mob tau suav nrog siv cov kab zauv hauv qab no:
Kev txheeb cais. Cov ntaub ntawv raug nthuav tawm raws li qhov nruab nrab ± tus qauv sib txawv. Kev txheeb xyuas cov ntaub ntawv tau ua los ntawm kev siv ib txoj kev tsom xam ntawm qhov sib txawv ua raws li qhov ntsuas qhov sib txawv tsawg kawg nkaus. Cov ntaub ntawv raug tshuaj xyuas siv SPSS software version 19.0 (IBM SPSS, Armonk, NY, USA). P<0.05 was="" considered="" to="" indicate="" a="" statistically="" significant="">
Cov txiaj ntsig thiab kev sib tham
Kev tshuaj ntsuam cov roj, surfactants, thiab co-surfactants rau ME. PG(phenylethanoid glycoside los ntawm cistanche)yuav luag insoluble nyob rau hauv cov kua paraffin thiab oleic acid, tab sis kev solubility nruab nrab tau pom nyob rau hauv IPM (Table II). IPM nce qhov diffusion coefficient nyob rau hauv daim tawv nqaij thiab ua rau kom nce permeation coefficient (17,18). Tsis tas li ntawd, IPM feem ntau raug xaiv rau kev npaj ntawm MEs vim nws paub zoo permeation txhim kho cov khoom thiab biocompatibility. Kev xaiv surfactant yog qhov tseem ceeb rau kev ua tiav ntawm MEs vim nws ua rau txo qis ntawm kev sib tshuam los ntawm kev tsim cov yeeb yaj kiab ntawm cov roj-dej interface (19). Hauv txoj kev tshawb fawb tam sim no, PG tau nthuav tawm ntau dua solubility hauv Cremophor-EL (40.193 mg / ml; Table II) piv nrog Tween -80 (28.051 mg / ml; Table II). Yog li ntawd, CremophorEL tau raug xaiv los siv rau hauv kev tshawb fawb ntxiv vim nws cov ntsiab lus solubility thiab nws cov qib toxicity tsawg raws li cov non-ionic surfactant. Tsis tas li ntawd, nws cov tshuaj aqueous tau pom zoo solubility ntawm PG. Qhov siab tshaj plaws solubility ntawm PG ntawm cov cosurfactants tau pom nyob rau hauv propylene glycol (48.714 mg / ml; Table II). Tsis tas li ntawd, propylene glycol muaj peev xwm tsim MEs nrog IPM thiab CremophorEL. Ua ke, IPM, CremophorEL, thiab propylene glycol tau siv los ua cov roj theem, surfactant, thiab cosurfactant, feem, rau kev tsim ntawm PG-loaded MEs. Kev tsim kho ntawm pseudo-ternary phase diagrams. Hauv qhov kev tshawb fawb tam sim no, cov duab kos duab tau tsim los xaiv qhov sib txawv ntawm cov khoom sib xyaw rau cov microemulsions, thiab cov chaw cim qhia pom tseeb O / WMEregion (Fig. 1). Kev sib raug zoo ntawm cov dej ntws ntawm stratum corneum thiab dermal permeation tau tshaj tawm yav dhau los (20), thiab cov thermodynamic kev ua haujlwm ntawm cov tshuaj hauv MEs yog qhov tseem ceeb tsav tsheb tom qab tso tawm thiab nkag mus rau cov tshuaj rau hauv daim tawv nqaij (20,21). ). Lub thermodynamic kev ua ntawm cov tshuaj nyob rau hauv ME nrog qis surfactant sib tov cov ntsiab lus tau pom tias yog ib qho tseem ceeb tsav lub zog rau kev tso tawm thiab nkag mus rau cov tshuaj rau ntawm daim tawv nqaij (22,23).
The decreased concentration of surfactant in dispersed systems may also increase the rate of drug release and its permeation in the skin (24,25). Thus, the water content ranged between 50 and 70%, while that of the surfactant and cosurfactant ranged between 20 and 45%. The microemulsion domain was determined by visual inspection for clarity and fluidity. The rest of the region in the phase diagrams represents turbid and conventional emulsions based on visual observation (Fig. 1). No liquid crystalline structure was observed using the cross polarizer. The area of the O/W ME region was expanded following the increase of the Km value (Fig. 1). These findings were consistent with previous studies, which demonstrated that a higher level of surfactant reduces interfacial tension of the colloidal solution more effectively, thereby improving the fluidity of the interface and increasing the entropy of the system (21,24). Thus, it is reasonable to speculate that the effect of CremophorEL on ME regions depends on the other ME components, especially the cosurfactant. The combination of short to medium carbon chain length alcohols, including propylene glycol, with single-chain surfactants, may lower interfacial tension due to increased fluidity at the interface. Additionally, medium carbon chain length alcohols may induce elevation of miscibility of the aqueous and oily phases due to the partitioning behavior between the two phases. Finally, in the presence of a Km ratio of 3:1, the ratio of the surfactant mixture to oil was 1:9 or 2:8. MEs prepared with a ratio of surfactant mixture to oil >2:8 yog turbid thiab tsis ruaj khov (Fig. 2).
Cov kev sib xyaw zaum kawg ntawm ME1-5 tau teev nyob rau hauv Table I. ME kev npaj thiab kev ua yam ntxwv. Lub cev muaj zog ntawm ME1-5 tau teev nyob rau hauv Table III. Cov txheej txheem disperse yog macroscopically zoo tib yam, homogeneous, thiab pob tshab, tsis muaj precipitates. Qhov nruab nrab qhov loj me ntawm cov MEs no nyob nruab nrab ntawm 30.56 thiab 79.21 nm (Fig. 3; Table III), nrog rau polydispersity-index qhov tseem ceeb ntawm 0.187 thiab 0.321 (Table III). Qhov no qhia tau hais tias ib qho ME uas muaj kev faib khoom nqaim. Tsis tas li ntawd, droplet loj nce nyob rau hauv kev faib ua feem nrog cov roj cov ntsiab lus tab sis txo nrog surfactant sib tov cov ntsiab lus. Qhov tshwm sim no tuaj yeem raug ntaus nqi los ntawm kev nthuav dav ntawm ME roj tub ntxhais, thiab qhov siab ntawm surfactant concentration forcefully txo cov roj-dej interfacial nro kom txo qis me me. Tsis tas li ntawd, ME viscosity tau nce siab vim qhov nce qib surfactant thiab dej tsawg. Cov pH qhov tseem ceeb ntawm tag nrho cov MEs poob rau hauv qhov tsim nyog ntawm 5.0-7.5 (Table III) thiab yog li tau sib xws nrog cov ntaub so ntswg ntawm daim tawv nqaij. Hais txog kev ruaj ntseg ntawm lub cev, tsis muaj theem sib cais, tawg lossis nag lossis tshuaj yeeb hauv ib qho ntawm cov MEs kuaj, qhia tias MEs muaj qhov txaus siab thermodynamic stability tiv thaiv centrifugation. Qhov kev ntsuam xyuas dye solubility tau qhia tias cov dej-soluble dye (methyl txiv kab ntxwv) faib ib yam thoob plaws hauv ME system, uas txhais tau hais tias cov tsim ME yog hom O / W (cov ntaub ntawv tsis qhia). Cov micrographs tau nthuav tawm ib leeg ME5 cov tee dej uas muaj cov duab puab kheej kheej (Fig. 4). Exvivo daim tawv nqaij permeation kawm. Lub permeation profiles ntawm tag nrho cov tsheb kuaj ua raws li xoom-order tso tawm kinetics (26,27) thiab ME5 muab lub siab tshaj plaws transdermal flux ntawm PG (86.795±0.23 µg/cm{{28} } } /h{29}}; Fig. 5; Table III). Hauv kev tshawb fawb tam sim no, cov txiaj ntsig ntawm cov roj cov ntsiab lus thiab cov khoom sib xyaw surfactant ntawm daim tawv nqaij permeation ntawm PG tau txiav txim siab. Cov txiaj ntsig tau qhia tias surfactants txhim kho daim tawv nqaij permeation los ntawm kev ua kom cov kua dej ntau ntxiv, tshuaj solubilization, thiab tshem tawm lipid los ntawm stratum corneum. Tus nqi permeation ntawm ME5 (86.795±0.23µg/cm-2 /h-1) tau nce ntau dua piv nrog cov permeation ntawm ME1 (69.57±{ {48}}.78, P=0. . . , P=0.0063, Fig. 5; Table III) Qhov no tau ua raws li cov txiaj ntsig ntawm kev tshawb fawb yav dhau los, uas cov thermodynamic kev ua haujlwm ntawm ME cov tshuaj thauj khoom yuav txo qis nrog kev nce qib ntawm surfactant (12,28). ). Lub viscosity ntawm ME5 (30.43 ± 0.12 mPa.s) qis dua piv nrog rau lwm yam ME1 (80.51 ± 0.87 mPa.s, P=0.0076), ME2 (47.52 ± 0.54 mPa.s, P{{88). }}.0089), ME3 (60.49±1.34 mPa.s, P=0.0094) thiab ME4 (43.27±0.21 mPa.s, P=0.0059).
