Nghien dm Y hpc Y Hoc TP. Ho Chi Minh * Tap 21 * So 5 * 2017
TOI U u HOA QUY TRINH Dlfeu CHE GIA MANG LIPID CAU TRUC NANO TAI MICONAZOL NITRAT
Nguyen Thi 'Thich', Pham Dinh Duy*
TOM
TATMuc tieu: Khdo sdt vd tm leu hoa mdt sSym to anh huang din quy tnnh diiu che gid mang lipid cau true nano tdi miconazol nitiat.
Phuang phdp: Qud trinh thiei kethuc nghiem vd tm uu hoa dugc thuc hien bang pKan niem Design-Expert.
Cdc yeu to can khdo sdt ti-ong quy trinh dmi cheNLC hao gom: lugng mg MN/ 100 ml THF, ti le tween 80 (%), ti li hdn hap lipid dtiea MN (%), toe do khuay (vong/ phut) vd thiri gian Idiudy (giay). Cdc tinh chai ciia NLC i^n dugc xdc dinh dedanh gid dnh huang cua cdc yeu to den quy trinh dieu cheNLC gam: kidi thuac hat trung Unh (nm), do rang day phdn bo'ldch thuac hd (span), hi soon dirih vd hieu suat bdt giie (%).
Kei qud: Ti le tween 80 vd ti li hSn hap lipid chiea MN dnh huong din Mch thudc hat trung Unh; khong co yeii toldido sdt ndo dnh huong deh ket qud span; lugng MN, ti li tween 80, toe do khu^, thdi gian khuay dnh huong din hi so&n dinh; mtatcd cdc yHi to khdo sdt deu dnh hu&ng d^ hieu suat bat giU. Sau khi t&i uu hoa, cdc yeu td'quy trinh dieu cheNLC nhu sau: lugng MN la 30 mg, ti le tween 80 Id 30%, ti le hon hgp lipid chiia MN la 10%, toe do Ihuay la 15.000 vong/ phiit vd thcri gian khuay Id 120 giay. Tieong ung, tinh chai NLC tdi miconazol co kich thudc hat trung Unh la 58,1 nm, hi soon dinh la 0,33 vd hieu su^ bat giit 80,5%.
Ket lu^m Quy tririh diiu che'gid mang lipid cm tdc nano tdi miconazol nitrat dugc tm uu hoa thanh cong.
Tu^khoa: Gid mang lipid caii true nano, miconazol nitrat, toi uu hoa.
ABSTRACT
OVTIMiTATlON OF PREPARING MICONAZOLE NITRATE LOADED NANOSTRUCTURED UPID CARBIER
Nguyen Thi Thich, Pham Dinh Duy *Y Hoc TP. Ho Chi Minh * Vol. 21 - No 5 - 2017:142 -149 Objective: The aim of this study is to investigate and optimize factors affecting the preparation of miconazole nitiate loaded nanostructure lipid carrier.
Method: The software Design Expert 7.1.5 was used for experimental design and optimization. Factors were investigated during the preparation of NLC including the amount of MN (mg)/ 100 ml THF, the tween 80 concentiations (percentage), the concentiation of lipid mixture and MN (percentage) and, stirring speed (rpm) and stirring time (s). The physicochemical properties of the NLC which were determined include the average particle size (nm), particle size distribution (span), the stability factor (percentage), the entiapment efficiency (percentage).
Results: The tween 80 concentiation, the concentiation of lipid mixture and MN affected ihe average particle size of NLC. None of the factors affected the span. Most factors affected the sterility factor. All of the factors affected the entiapment efficiency except the concentration of lipid mixture and MN. The optimized process had 30 mg amount ofMN/100 ml of THF, 30% tween SO and 10% of lipid mixtiire and MN with 15,000 rpm/min of stirring speed in 120 seconds. Correspondingly, the physicochemical properties of miconazole nitiate loaded NLC had an average particle size of 58.1 nm, stability factor of 0.33% and entiapment efficiency of 80.5%.
Conclusion: The process (^preparing miconazole nitiate loaded nanostructure lipid carrier was successfully
* Bp mon Bao Che, Khoa Dugc - Dai hpc Y Dupe TP H6 Chi Minh
Tdc^ liin lac: TS. Ph?m Dinh Duy DT: 0908832827 Email: [email protected] 142
Y Hpc TP. Ho Chi Minh * T^p 21 * So 5 * 2017 Nghien cthi Y hpc
optimized.
Key words: Miconazole nitiate, nanostructure lipid DATVXNDE
Gia mang lipid cau tnic nano (NLC) la tieu phan nano ran. Voi uu diem vuot trpi so voi cac dang bao che Ihong thucmg cung nhu cac d?ng tieu phan nano the h^ trucfc ve tinh on dinh vat 1^ cao, kha nang tai hoat chat, kha nang bao ve ho?t chat, tinh tuong thich sinh hpc, tinh thain, tac dung gii> ain cho da va kha nang ngan chan tia UV...'*'. NLC ngay cang dvrgc uu chuong trong san xuat dupe phain noi chung va dang thuoc dimg ngoai noi rieng.
Miconazol nitrat la hoat chat thuoc nhom azol, day la nhom thuoc dime su dung trong dieu tri benh UEun da. Miconazol nitrat co do tan trong nuoc kem (<1 mg/ ml) do do sinh kha dung ciia cac che pham co chiia ho?t chat nay khong cao, hieu qua tri heu thap'^'. Vi vay, viec ling dung NLC tai miconazol nitrat se lam tang nong dp hoat chat trong che phain, tang tinh bam dinh tren da, kiem soat qua trinh phong thich hoat chat tai dich tu do lam tang hieu qua dieu tri va giam tac dung phu cua che pham.
Trong quy trinh dieu che, c6 nhieu yeu to anh huong doi tinh chat NLC. Ben canh d6, vdi mong muon dieu che dupe NLC co tmh chat hoan thien hon tii nghien cihi ctia tac gi^ Le Khac Tuacn va crang su<2', nen muc tieu aia nghien ctiu nay la xac dpih duoc mpt so yeu to CO ihe anh huong quy trinh dieu che NLC va toi im hoa c^c yeu to do.
NGUYfiN U6U - PHl/ONG PHAP NGHlfeN CUU
Nguyen li?u
Hoat chat miconazol nitrat (MN) dat tieu chuan BP 2013, xuat xii An Dp. Compritol 888 ATO, capryol 90 dat tieu chuan USP 33, xuat xii Phap va glyceryl mono stearate (CMS) dat tieu chuan BP 2007, xuat xii Trung Qu6c, dirpc sis dvng lam pha lipid ciia NLC. Tween 80 dat tieu chuan USP 33, xuat xii Phap va propylene glycol
carrier, optimization.
(PG) dat tieu chuSi BP 2007, xuSft xii Trung Quoc, dupe sii dung lam chat di?n hoat va dong dien hoat. Tetrahydrofuran (THF) dat tieu chueun phan tich, xuat xii Trung Quoc, dupe dimg 1 ^ dung moi trung gian hoa tan. Nuoc sir dung la nuoc cat 1 lan.
Phuang phap
Bieu chfgid mang NLC tdi miconazol nitrat Dieu chehon hap lipid
Moi lan dieu che tuemg ling voi 100 g hon hpp lipid.
- Thanh pKan h6n hpp lipid bao gom: 63%
Compritol 888 ATO, 7% Capryol 90 va 30%
CMS.
- Cach thliy h6n hpp Compritol 888 ATO va Capryol 90 6 nhiet dp 80-85 °C, dimg may khuay trpn deu voi toe dp 300 vong/ phiit, trong 60 phiit roi de nguoi dupe hon hpp 1. Can GMS diing ti Ie so voi hon hpp tren viia de nguoi (hon hpp 1:GMS = 70:30). Dun chay hon hpp nay, tiep tiic trpn deu voi ^ dp 300 vong/phiit, trong 60 phiit. De ngupi, bao quiin tranh anh s ^ g . Di'gu chehon hgp lipid chiea MN thong qua viic su dung dung moi THF
Moi Ian dieu che tuong ling voi lupng dung m6i sii dung la 100 ml THF.
- Thanh phan dieu ehe gom: 20-50 mg MN, 3,5 g hon hpp lipid va 100 ml THF
- Sii dung may co quay Biichi R-210 6 toe dp quay 3 de hoa tan MN va hon hpp lipid vao THF 6 nhi?t dp 55 'C trong 15 phiit, sau do l o ^ bo THF bing c^eh bat he thong hiit chan khong. Co quay trong 90 phiit.
Diiu cheNLC bang phuong phdp vi nhd tuong M6i Ian dieu che hxong ling voi 20 g vi nhu tuong.
- Thanh phan dieu che gom: 5-15% hon hpp lipid chiia MN, 10-30% tween 80,6% propylen glycol va nuoc cat vua dii 100 %.
Nghien ciru Y hpc
- Can hon hpp lipid chiia MN, tween 80, PG Iheo diing ti le ( ^ khao sat. Lam ehay hon hpp lipid chiia MN, tween 80 va PG trong coc thuy tinh 2 lop on nhi^t 6 80-85 °C trong 30 phiit, song song khuay tir 6 toe dp 3. Cho tu tCr nuoc cat vao hon hpp trong coc on dinh nhiet, tiqp tue khuay tli d^' phan tan deu 2 pha. Sau khi da cho het nuoc vao tiep tuc khuay tir trong 5 phiit. Dimg may dong nhat hoa khuay b cac toe dp (n vong/phiit) va thoi gjan (t giay) can khao sat. Sau do, pha loang theo ti 1^ 1:10 bang each dimg bom tiem thliy tinh (da dupe lam nong d 80-85 "C) hiit 10 ml vi nhij tuong cho vao 90 ml nuoc cat (da dupe lam lanh 6 0-2 <!), duoi lue khuay 6.000 vong/ phiit trong 1 phiit Bao quan 6 nhiet dp khoang 8 C
Khdo sdt cdc dac tinh cua NLC Xdc dinh hieu sudi bat giie hoat ch^
Ffieu suat bat gju thuoc ciia h^t NLC dupe xae dinh theo phuong phap thiia trii. Lupng MN toan phan (m^) va lupng MN tu do (bao gom lupng tan trong pha nuoc va ket tinh tren bS mat hat) (mid) dirpc xac dinh bang phucmg phap tao phiic mau voi dung dich xanh bromocresol 0,1 mM trong d&n dtrat pH 3,5. Phiic hpp MN - bromocresol dupe chiet bang eloroform va do dp hap thu d buoc song 421 nm°fi. MSu de dinh lupng MN toan phan ehinh la he phan tan NLC sau dieu che. Trong khi do, mau de dinh lupng MN tu do la phan dung djch trong suot thu dupe 6 phan duoi ong sieu Ipc ly tam Vivaspin®
6 (Sartorius) sau khi ly tam 4000 vong/phiit trong 30 phiit.
Hiit 1 ml mau can dinh lupng eho vao bmh chiet, them 5 ml dung dich dem amoni acetat p H 3A 10 ml dung dich xanh bromocresol 0,01 M lac nhe roi chiet bang 5 ml chloroform. Lam 4 lan nhu vay, moi Ian lac manh trong vong 2 phiit.
Gpp dich chloroform thu dupe tOr 4 lan chiet dem do quang 6 buoc song 421 nm. Ket qua dupe the hien bang ket qua trung bnih ctia 3 Ian lap lai.
Y Hoc TP. Hb Chi Minh * Tap 21 * Sfi 5 * 2017
Sau khi lupng miconazole toan phan va tu do dupe xac dinh thi hieu suat bat gi& thudc ciia NLC dupe tinh bang cac cong thiic sau:
Lupng MN bj bat giir mt=mip-mid
Hi^u suat bat giii (Entrapment Efficiency - EE) thuoc cua hat
Xdc dinh kich thuoc vd su phdn bo kich thuoc hat Kich thuoc hat NLC va phan bo kich thuoc hgt dupe xac dinh bang may LB550, Nhat Iheo nguyen tac tan xa laser. Dich NLC dupe pha loang vdi nuoc cat theo ti le 1/100 6 nhiet dp phong truoe khi tioi hanh do. Lupng mau can dimg cho moi Ian do khoang 3 m l Kich thuoc hEtt trung binh co dupe dua tren ket qua 3 Ian do.
He so on dinh
He so nay dupe xac dinh dua tren phuong phap cua Tang va cong suO. Sau khi dieu che NLC, hiit 10 ml dich phan tan cho vao ong Iy tam 15 ml, Iy t ^ 5 chu ky. Moi chu ky mau dupe Iy tam voi toe dp 3.750 vong/phiit trong 1 gio, sau do nghi 20 phiit. Hiit lay phan dich trong phia fcren va do kich thuoc hat. He so on dinh dupe tinh tiheo cong tiiiic: KE= (Ro - R)/Ro X 100%, vol Ro la kich thuoc hat truoe khi Iy tam va R la kich thuoe hat sau khi ly tam. Ket qua dupe the h i | n bang ket qua trung binh cua 3 Ian lap Iai.
Thiei kesdng IQC vd toi uu hoa cdc yeii to dnh huang trong quy trinh dieu chf NIC
Cae bim so ciia quy ttinh dieu che NLC cho cae thiet ke ihuc nghiem dupe liet ke trong Bang 1. Ben canh do, cac birai phu thupc dupe xac dinh sau moi thuc nghiem la cac dac tinh ciia NLC nhu: yi - kieh thuoc hat trung binh (nm), yi - dp rpng day phan bo kich thuoc hat (span), ys - he so on djnh (%) va y4 - hi?u suat bat giii (%).
144
Y Hpc TP. Hb Chi Minh * T^p 21 * So 5 * 2017 Nghien cmi Y hpc
Bang 1. Cac yeii tScSn Idido sdt trong quy trinh dim cheNLC Y4ut6(blinqiiyMnh)
LwngMN/IOOmlTHF 771$ tween 80 Ti 1$ hSn hgrp lipid chi>a MN
Ticd^ldiuiy Tti&i gian IthuSy
Oonvf mg
% %
V6ng/ptiCrt GlSy
Biin s i Xi X2 X3 X4 X5
Gi6i ii^n difoj 20 10 6 6.000
20
Tmng tam 35 20 10 15.000
70
Gidi ti^n tren 50 30 15 24.000
120 Viec khao sat su anh huong ciia cac y&i to
trong quy trinh dieu che NLC dupe thi^c hi?n voi sir h6 trp ciia phan mem Design-Expert 7.1.5 trM qua cac giai d o ^ : sang Ipc cae yeii to anh huiimg, khao sat sp^ tucmg tac giiia cac yeu to iinh huong den tinh chaft NLC va xay dijfng phuong trinh hoi quy, Biing 2. Viee sang Ipc cac yeii to anh hudng dupe tiKi hanh dua tren thiet ke giai thiia phan do?n, sau do cac dti Ii$u thuc nghi&m dupe phan tich fhong ke va (h^ hien ket qua bang bieu do Pareto. Doi voi 3 giai doan e6n lai dupe tien hanh dua tren phuong phap be mat d i p ling voi thiet ke cau tnic trung tam (Response Surface Methodology - Central Composite Design), sau do cae du U$u th\rc nghi?m dupe phan tich ihong ke va the hien ket q u i bang bieu do Pareto, phuong trinh hoi quy ciia Y.
Viec toi uu hoa mpt so yeu t& inh huong trong quy trinh dieu che NLC eung dupe t h i ^ hien voi su hS trp cua phan mem Design-Expert 7.1.5: sii dung dii lieu thue nghiem tir mo hinh ttuet ke cau true trung tam tioi hanh toi uu hoa cac bien so quy trinh dau vao va bi&i phy thupc daura.
Thuc nghi$m kian chiing
Dieu ehe 3 16 h^ phan tan NLC theo quy trinh toi uu roi ti«i hanh danh gia cac tinh chat ciia NLC. Sau do so sanh cac gia tri d u doan tir phan mSm Design-Expert 7.1.5 vcri gia trj trung binh cua 3 Ian thuc nghiem. Viec so Bdng ZCdcmd hinh vd da liiu thuc nghiim.
sanh nay dupe dua tren gia tri "Bias" (%) = I gia tri d v doan - gia tri thyc n g h i ^ | /gia trj d u doan x 100%.
KET QUA VA BAN L U ^ N Sang Ipc cac yeu to anh huong
Muc dich eiia khao sat nay la tim ra y^u to nao anh huong co y nghia d&i cac tinh chat ciia NLC, tir do co the logi bo nhiing yeu to khong quan trpng dong thoi lam giam so lupng Hwfc nghiem cho cac khao sat sau. Ket qua nghien ciiu sang Ipc cac yeu to i n h hu6ng iheo mo hinh yeu to phSn doan dupe the hi^n trong Bang 2 ( T N I - 8 ) .
Dua vao bieii d^ Pareto, EBnh 1, co the n h ^ dinh ket qua nhu sau:
- Cae yeu to lupng MNAOOml THF, ti 1?
tween 80, ti le hon hpp lipid ehiia MN va thai gjan khuay anh huong co y nghia den kich thuoc h a t Mnh IA.
- Trong cac yeu to khao sat khong co y&a tS nao anh huong co y nghia d&i tmh chat span thong ke, Hinh IB.
- Cae yeii to lupng MN/lOOnU THF, ti Ie tween 80, ti le hon hpp lipid chiia MN va tiicri gian khuay anh huong co y n g h ^ d m he so on dinh,lfinhlC
- Chi CO yeu to thoi gian khuay anh h u o i ^ co y nghia d&i hieu simt bat giii, Hinh ID.
Giai do^n TN 1 2 3 4
iilid liinti tlivc nglii$m X1
50 20 20 50
X2 30 10 10 10
X3 15 IS 5 15
X4 24.000 24.000 24.000 6.000
X6 120 20 120 120
DLFli$uttivcngt)i#m (n=3) y i
1081±121 3694±427 111±9 3668±506
V!
6,92±1,32 0,8610,07 11,67±3,45 0,79±0,12
y»
0,85JO,02 0,79i0,04 0,33±0,06 0,63±0,05
y< 73,6i2,3 65,3±1,7 79,212,5 71,7*0,9
N g ^ e n cihi Y hoc Y Hoc TP. Hb Chi Minh * T^p 21 * So 5 * 2017
Giai do^n
u
f ^
o o,
it
•D TN
5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Mo tiinli ttiut: ngiii^m
X i
20 60 20 60 60 20 20 60 50 50 20 20 35 35 35 60 35 20 35 35
xz 30 10 30 30 10 30 30 10 30 30 10 10 20 20 20 20 20 20 10 30
xa 15 5 5 5 5 16 5 15 16 5 15 5 10 15 10 10 10 10 10 10
X 4
6,000 6000 6.000 24.000 6.000 6.000 6.000 6.000 24.000 24.000 24 000 24.000 15.000 15.000 24.000 15.000 15.000 15.000 15.000 15.000
xs 20 20 120 20 120 120 20 20 20 120 120 20 70 70 70 70 20 70 70 70
DOIieuttivcngiii^ (n=3) yi
536±85 11181174
36±1 27713 11218 36661230
2411 24741342
12616 2411 296117 211112 7616 282110
4513 10113 104112 4212 24481121
10114 yi 12,7311,57 31.1712.13 0.6710,02 1,0610,04
- - - - - - - - -
-
ys 0.7910,03 0,8910.06 0,3110,02 0.6210,01 0,5710,04 0,1610,05 0,3910.04 0,7210.01 0,2810.02 0,4010,03 0,4310.05 0,6110,03 0,2810.01 0,3310,02 0,3210,01 0,3110.03 0,4010.02 0,3510.05 0,5610,02 0,2810.05
42,710,3
»
20,811,5 53,611,7 41,412,0 85,011.2 68.812.3 41.110.2 67.910.8 60.510.9 76.611,3 69,910,5 70,611,7 80,412,2 63,111,1 91,411,6 65,612,3 54,112,1 82,510,1 57.810.4 76.910.9 lipid dtua MN (%); xa: toe do khtmf
ys hi som dinh (%); y*. hieu suSi bat giii
'tiut& inh hucmg
Hinh 1. Biai do Pareto cim cdc y^ to anh hiiu suM bit giir (D)
kich thuac hat trung Unh (A), span (B), hisoSn dinh (C) vd
146
Y Hoc TP. Hb Chi M m h * T^p 21 * So 5 * 2017 Nghien cihi Y hpc
Khao sat s u hnmg tac giiia cac yeu to anh huong
Sau khi n h | n djnh dupe cac yeu to ciiinh anh hudng cd y nghia den cac tmh chat ciia NLC va nghien ciiu tiep tuc khao sat su tuong tac giiia cac yeu to dd anh hudng d^en kich thudc trung binh hat he so on dinh va hieu suat bat giii ciia NLC. Ket qua khao sat dupe ihe hien trong Bang 2(TN9-16).
Dua vao bieu do Pareto, Hinh 2, cd the nhan djnh ket qua nhu sau:
- Hai yeii to ti le tween 80 va ti le hon hpp lipid chiia MN anh hudng quan trpng nhat d&i kich thudc hat tiung binh, Hinh 2A.
- Lupng MN/100 ml THF, ti le tween 80, tcfc dp khuay va thdi gian khuay ed anh hudng den he so on dinh. Trong do, yeu to thdi gjan khuay anh hudng quan trpng nhat va cd su tuong tac anh hudng vdi cac yeu to edn lai, FDnh 2B.
- Cac yeu to lupng MN/100 ml THF, ti le tween 80, ti Ie MN/ hon hpp lipid, toe dp khuay, thdi gjan khuay deu co tae dpng anh hudng den hi|u suat bat giii. Trong dd, Ihdi gian khuay cd tac dpng anh hudng quan trpng nhat den hieu suat bat giu va cd su tuong tac inh hudng vdi cac yeii to cdn igi, Hinh 2C.
— 1 — r — r 1 2 3 4 5 6 7 8 9 10 IE 12 13
Y^u 10 inh hirung
51,45-
3 8 ^ 9 -
25,73- X:
12,86-
0,00- U U ''Jjj'XiX.X,
nlffp^
y y y U y i j I j y g _
1 2 3 4 5 6 7 8 9 10
Yeu 16 anh hucmg
Hinh 2. Bim do Pareto visu tuong tdc cua cdc yeu. to dnh huong den kich thudc hat tiTing binh (A), hi sd'oh djnh (B) vd hieu su^ bdt gia (C).
Nghi@n cuu Y hpc Y Hpc TP. Hb Chi Minh * T | p 21 * So 5 * 2017
Xky dung phuong trinh hbi quy De xay dung dupe phuong trinh hoi quy ciia cac HOT phij thupc y, cac tiii^c nghiem vdi s& lifu trung tam ti^ tuc dupe thiet ke, Bang 2 (TN 17 - 24). Ben canh dd, vi@c xay dung phuong trinh phai dupe di;ra tren tat ca ket qua ciia 24 thuc nghiem da tien hkih. PhSn m&m Design Expert 7.1.5 xCr ly dii Ueu ihuc nghiem bang ANOVA va de xuat cac phuong trinh hoi quy nhu sau:
Kich thuac hat tmng ldnh
Ln(yi) = 17,41 - 0,01.xi - 1,04.X2 - 0,11.X3 - 0,0002.X4 - 0,03.X5 - 0,005.xi.X3 + 0,18.1O6.xi.X4 - 0,0003.xi.X5+ 0,0006.X2.X5- 3,9.10*.X3.X4- 0,002.X3.xs + 0,02.X22+0,02.X32
H$ so6n djnh
y3= 1,63 - 0,009.xi- 0,029.X2- 3nO*.X4- 0,009.X5 + 10^.xi.X5+ 10*.X2.X4+ 8,6.ia^.X2.X5+ 1,15.10^X4.X5 Hi$u sulCt batgia
Bdng 4. KA qud tdi mi hoa va du dodn
y4= 40,78 + 0,006.X5+ 0,24x4 Tbi m i hoa cac y^u to Anh hu6ng
Du lieu d B ^ g 2 dupe xii ly b ^ g plmn mem Design-Expert de toi uu hda c^c yeu to ^inh hudng nhu lupng MN/100 ml THF, ti le tween 80, ti 1| MN/ hdn hpp lipid, toe dp khuay, thdi gjan khuay va dua ra ket qu^ dy doan eiia kich ihudc hgt trung binh, h? so cii djnh va hifu suat bat giii tuong ling. Ket qua dupe trinh bay d Bang 3 va 4.
Bdng 3. Ket qud ocie ly thdhg M cua cdc bim phu thuoc
C h i s 6 t h i n g ke D $ l $ d i c h u l n
T m n g blnti C.V. %
R' A d f R ^ A d e q Precision
y i 0.39 6.38 7.18 0.97 0.94 15.57
y3 0.09 0.46 20.71
0.76 0.65 13.01
y< 11,27 67.19 16.76 0.61 0.46 10.05
Biin 86 X1 X2 X3 XA Xs
T f i n LtJ^ng MN/100 ml T H F
T i i g Tween T l i§ h3n h ? p sdp vd M N
T 6 c d $ l c h u 4 y T h d i giati Ithu^y
G i i t r j 30 (mg)
3 0 % 1 0 % 15.000 (v6ng/phi»)
120(gi9y)
B i ^ n ph\f t h u ^ c yi ^ ya
y^
TSn Kich t h u * ^ h^t ^ n g binh
H$ s& &T\ d\r\h IHi^u sulit bat giO
D u d o d n 59,2 nm 0.35%
77,7%
Miic do mong mum: 0,88 Thuc nghiem kiem chung
316 he phan tan NLC dupe dieu che dua tren cac bien so da toi uu hda, sau dd dupe ti&i hanh danh gia cae tinh chat ciia NLC nhu kich thudc hgt trung binh, he so on djnh va hi$u suat bat giir de so sanh vdi gia tri dtr doan. Ket qua dupe th&'hi?n d Bang 5.
Bdng 5. So sdnh kH qud kii qud du dodn vd thuc nghiim
T i n h c h i t K i c h t h u 6 c h 9 t t n j n (
binh H $ s 6 6 n tiinh i i i ^ u s u l i t l j S t g i O
d o d n 59.2 nm
0.35%
7 7 . 7 %
Gid t l i t l i i , c n g h i # m (n=3) 58.1±15.4nm
0.3310.04%
80.6±2,1%
B i a s
(%)
1.9 5.7 3.6
Gia tri "Bias" cang nhd cho thay kei qua tiiuc nghiem kiem ehiing cang phii hpp vdi su du
doan. Doi vdi kieh Ihudc hgt trung binh, gia trj
"Bias" la 1,9% cho ihay ket qua ihuc nghi?m phii hpp vdi du doan ciia phan mem Design-Expert Trong khi dd he so on dinh va hi|u suat bat giii cd gia tri "Bias" Ian lupt la 5,7% va 3,6%, cac gia tri nay tuong doi cao hon so vdi kieh thudc hat tnmg binK Dieu nay x^y ra vi gia tri "R- Squared" va Adj R-Squared ciia phuong trinh hoi quy ciia 2 tinh chat nay khdng cao (0,76; 0,65 va 0,51; 0,46), Bang 3.
Tuy ket qua thuc nghiem cd sai khae so vdi dij doan song cac tinh chSft ciia ihuc nghiem toi u u van dap ling dupe yeu cau eiia he pMn tan NLC nhu kieh thuoc hat trung binh la 58,1 nm;
h | so on djnh la 0,33; hi$u suSt bat giu 80,5%.
PhSn b6 kich thudc hgt ciia thuc nghiem tffi uu dupe tiie hien d Hinh 3.
Y Hpc T P . H b C h i M i n h * Tap 21 * So 5 * 2017 N g h i e n curu Y hpc
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HIBJI 3. Phan boldch thudc hat ciia thuc nghiim tdi uu
KETLUAN
Tat ea cic yeu td khao sat deu anh hudng dm quy trinh dieu die NLC. Tuy nhien, khong c6 yeu to khao sat nao anh hudng den dp rpng day phan bo kich tiiudc hat. Thuc nghiem tdi u u dat dupe lupng MN/lOOml THF la 30 mg, ti le tween 80 la 30%, ti Ie hon hpp lipid chiia MN la 10%, toe dp khuay la 15.000 vdng/ phiit va thdi gian khuay la 120 (gjay). Ben canh dd, tinh chSit NLC tai miconazol nitrat dat dupe nhu sau: kieh ttiirdc hat trung binh la 58,1 nm, he so on dinh la 0,33% va hieu suat bat gjir 80,5%.
TAIUEUIHAMKHAO
1 Al-Badr AA, (2005). Miconazol Nitrat: Comprehensive Profile. Profiles of Drug Substances, Exripients, and Related Methodology, ed. AA. Al-Badi and A.K. Dash.
Vol. 32 Elsevier
2. U Khflc Tuin and Phpn Dinh Duy (2017). Diiu che gia mang lipid ciu true nano chtra nuconazol niliat bang phuong phap vi nhu tuong. Top chi Duoc hpc. S6 494 nfim 57(06/2017): p. 21-25.
Diameter i\im)
Fedeisen M and Kassing MR, (1990). Miconazole and miconazole nitrate chewing gum as dnig delivery systems - a practical application of solid dispersion techmque.
Drug Developnient and Industrial Pharmacy. 16(1); p. 55- 74.
Souto E and Miiller R (2007) Lipid Nanoparticles (Solid Lipid Nanoparticles and Nanostructured Lipid Carriers) for Cosmetic, Dermal, and Transdermal Applicahons, in:
Nanoparticulale Drug Delivery Systems, pp 213-233. CRC Press
Tang JG, Xia Q, et al., (2010). Storage Stability of Alpha- Lipoic Add-loaded Lipid Nanoparticles. TTte Chinese Journal of Process Engineering. 10(2): p. 332-338.
Wtobel K., Wrobel K., de la Garza Rodriguez IM, Lopez- de-Alba PL, and Lopez-Martinez L, (1999). Determination of miconazole in pharmaceutical creams using intemal standard and second derivative spectrophotometry Jourtwl of Pharmaceutical and Biomedical Analysis 20(1-2): p.
99-105
Ngdy nhan bdi bdo:
Ngdy phdn bien nhdn xet bdi bao:
Ngdy bdi bdo dugc dang:
10/07/2017 15/07/2017 05/09/2017
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