• Nghien CIFU — Ky thuat
ora//y desintegrating tablets of metoclopramid.HCI 10 mg were successfully prepared at of 10,000 tablets scale and potentially produced at industrial scale.
Tdi li^u t h a m k h d o
1. Abdelbary G, Eouani C, Prinderre P, Joachln J, Reynier Jp. Piccerelie Ph (2005), •'Determination of In vitro Disintegration Profile of Rapidly Disintegrating Tablets and Correlation with Oral Disintegration", Inter J. Pharm. 292, pp. 29-41.2. ASEAN (2005), Asean Guideline On Stability Study Of Drug Product. Update revision: 22 February
2005, 9th ACCSQ-PPWG Meeting. Philippines
3. CD ROM USP 32 (2007)
4. Frank J. Tornetta. (1969), "Clinical Studies With the New Antiemetic, Metoclopramide", Current Researches Vol. 48, No. 2, p.198-204
5. Guidance for Industry Orally Disintegrating Tablet (2007), U.S. Department of Health and Human Services, Food and Drug Administration (FDA), Center for Drug Evaluation and Research (ODER)
6. Yourong Fu, Shicheng Yang. Seong Hoon Jeong, Susumu Kimura, & Kinam Park (2004), "Orally Fast Disintegrating Tablets: Developments^
Technologies, Taste-Masking and Clinical Studies', Critical Reviews in Therapeutic Drug Carrier Systems, 21(6). p.433-475.
Pha che thu* nghiem dung dich khu* trung dung cu ngoai khoa va dung cu noi soi
sur dung tai benh vien
• 9 • • •
Tran Hihi Tam', Ton That Quynh Trung^, Ton Nir Quynh Nhir^, Pham Thanh Phong^
' Trung tdm Kiem chudn Xet nghidm TP. Ho Chi Minh - Trung tam Y khoa Phuac An (HEPA) D $ t v a n d e
Dd hgn chd nguy c a bung nd nhidm tning bgnh vign vdi cde chiing vi khudn da dd khdng khdng sinh, vigc t h y c hdnh chdng nhidm khudn bgnh vign vdi nhidu hlnh thdc khdc nhau n h u k h d khudn, tigt khudn, x d ly dd vdi, phdng chdng n h i i m khudn cdc thu thugt xdm ldn, phdng ngua gdy nhidm eho nhdn vign y td,... da d u y c BO Y td quy djnh nghigm nggt '^'.
Nhu cdu vd cdc sdn phdm tigt triing eiia ngdnh y td Id mgt nhu edu edp thidt. Trdn thj t r u d n g , cdc sdn phdm tigt tning ehii ydu cd ngudn gdc ngogi nhgp ciia cde nhd sdn xudt Johnson & Johnson, Anios, B. Braun; cdc cdng t h u c t h u d n g chi ghi ten hogt chdt sdt khudn chfnh, khdng ghl ndng dg cy thd eung n h u cde thdnh phan cd tdc dyng phy try, chdng an mdn, mat khac cdc sdn phdm ndy cd gia thdnh t u a n g ddi cao so vdi dieu kign kinh td va nggn sdch ciia cdc benh vign d Vigt Nam '^'.
Chung tdi da nghien c d u thanh cdng dung djch tigt tning tay nhanh vd dung djch tigt tning dyng cy ngi soi s d dyng trong bOnh vign, vdi nhidu u u didm vd mgt tigt tning, dng dgng va hiOu qud kinh td'"*^.
Tuy nhidn, trudc khi tiOt tning, cdc dyng ey ngogi khoa vd ngi soi can phdi d u y c k h d tning de khdng Idy nhidm cho nhdn vidn y td vd mdi trudng tning qud trlnh vgn chuydn vd x u 1^ tigt tning, vi vgy chung t6i tidn hdnh dd tdi nghidn c u u bdo che sdn phdm dung djch khu" tmng dyng cy ngo?i khoa vi dyng cy ndi soi dd s d dyng tgi tjgnh vign, nhdm mgc dich tlm ra mgt san phdm cd cdng dyng k h d nhidm tuang t y n h u cdc san phdm ngogi nhgp, nhung gid thdnh rd han.
Doi t u ^ n g va p h u a n g phap nghien
CCPU D o i t u g ' n g
Nghidn c d u bdo chd, t h d tdc dyng khdng khudn, khdo sdt thdi gian tidp xiic, khao sat tfnh
' Nghien CLPU - Ky thuat
kfch ung cua dung djch td dd tlm ra cong thdc tdi uu cho san phdm dung dich khu nhiem dyng cy ngoai khoa vd nOI soi.
- Didecyl dimethyl ammonium cloride: 10%
- Chdt dign hogt: 2%
- Chdt tdy rda khdng tao bgt, chdt chdng dn Phuang phap nghien cdu
Pha chi dung djch ^* ^-^
Thdnh phan edng thuc:
1 >y.* . . i . . 1 ,. ! . » 1
l l , - I 1 • , .1 . 1 ! . » 1
md
Huftic cdt
Khu^y a4u I
Khudy ddu i
Khu^y ddu
i
Loc
i
Vao chai,
i
dan nhan, dong hop
n: 6,6%
- Huang, ma Quy trlnh phe DongTT
* •
can can
DongTT
j 1
J, nudc cdt: vda dii ehd:
Didecyl dimethyl ammonium cloride
Chdt diOn hogt
Chdt tdy n>a, chdt chdng an m6n
Mau, hucng, mrtfc vdO
Chai sgch, kho
Nhap kho
Hinh 1: So'dd cac buoc pha che sin phim Phuang phap kiem soat, kiem nghigm: theo
TCCS (duyc xay dyng tren quy md 100 lit).
- Kidm nghigm bdn thanh pham.
- Kiem nghiem thdnh pham.
Bang 1: Cac chl tiiu kiim nghiem bin thinh phim va thanh pham
Tiiu chi kiim b^ Yeu cau khi kiim tra Ban ^} Thanh pham Dung djch mau xanh nhgt,
c6 miii dgc trung, trong sudt The tich trung blnh mOt d o ^ vj
nho nhat
1 lit ±5%
Do ddng deu ve the tich.
(20 chai)
2 chai c6 dp lOch ± 7,5 % so vdi thd tich trung binh vd khfing co chai ndo lOch qud ± 15 % so vdi X the tich trung binh.
Djnh tinh:
Didecyl dimethyl amoni clorid Duang tinh Dinh luyng:
Didecyl dimethyl amoni clorid Giai han: 100g/chai ± 5%
Ghi chi: [XJ la tiiu chi tuong Ong can phii kiim tra
SD 434
N A M52)
• Nghien CLFU - Ky thugt
Thu' nghiim sing IQC ndng dd cua chit di^t khuin didecyl dimethyl ammoni chlorid, th&i gian tiip xuc ddi v&l khi ning tiit khuin cua dung dfch trin vl khuin E. coll ^'^^
Khio sit ndng dd chit di$t khuin Ndng dO dung djch t h d nghigm d u y c thidt kd theo bdng d u d i ddy:
Bdng 2: Ndng dd chit tiit khuin tmng dung djch thu' nghiim
Ky hiiu dung djch Ndng d^ didecyl dimethyl thir nghlgm ung vii ammoni chlorid
ctfc ndng d<i (%w/v)
DDAC 5% 5.0
DDAC 7% 7,0
10.0 Chiing vi khudn t h d nghigm: Escherichia coii ATCC 25923
Mdi trudng nudi cdy: Soybean-Casein Digest Agar
Nhiet dO: 32,5 ± 2,5 C Thdi gian: 18 ddn 24 gid Phuxmg phip thu" nghiim Cdch ddnh gia khd nang digt khuan - S a dd sd log ciia sd vi khudn sdng sdt/ ml trong dung djch digt khuan cd thd s d dgng dd tinh Chung s y Idm gidm sd vi khudn theo thdi gian.
- Cong thdc tfnh:
K=(1 / t ) ( l o g N o / N ) Trong dd:
K: Id hdng sd qud trlnh digt khudn
t: Id thdi gian (tinh bdng phiit) dd sd vi khudn gidm tuNoddnN
No: Id sd luyng vi sinh vgt ban ddu (CFU/ml) N' Id sd vi sinh vgt sau ciing (CFU/ml).
Khio sit anh hu^ng cua th&i gian tiip xOe ddi v&i khi ning diit khuin
v d mgt nguyen tdc, thdi gian tidp xiic cdng Idu thi kha ndng k h d nhiem cdng tdt. Tuy nhidn, ndu thdi gian tidp xiic lau qud cd thd gdy dn mdn dyng cy, khdng phCi h y p yOu cdu tigt triing dd tdi s d dgng. VI vgy, phai khdo sdt thdi gian tidp xuc dd nit ra kdt luan vd thdi gian ngan nhdt ma dung djch phdt huy tdi da kha ndng k h d trung.
Bdng 3: Th&i gian t dung djch
3 xdc cin khio sit ci^a
Ky hiiu dung dfch thir nghlgm img vii
thiri gian tiip xic DT1 DT2 DT3 DT4
Thiri gian tiip xic (phit)
10 15 20 25 ThO' nghidm m& rdng trin nhieu chung vl khuin l""
Sau khi xdc djnh d u y c nghigm thdc, thdi gian tidp xiic tdi u u , dO pha loang phii hyp, chiing tdi sd tidn hdnh t h u trdn nhidu chung vi khudn ddi vdi nghigm thdc da xdc djnh d u y c .
Chiing vi khudn t h d nghigm:
- Escherichia eoli ATCC 25923 - Bacillus subtilis PY 79
- Pseudomonas aeruginosa ATCC 27853 - Staphylococcus aureus ATCC 25922 - Mycobacterium BCG
- Samonella - Shigella
Mdi t r u d n g nudi cdy: Baird Paker, Cetrimide, Hoektoen, EMB, TSA.
P h u a n g phdp t h d nghigm, each ddnh gid khd ndng digt khudn: t u a n g t y mge t h u nghlgm sdng IQC.
Danh gii tinh an toin ctia san phim sau khi pha chi trin nguriri sir dyng ^^
Tinh an todn trdn ngudi s d dyng eua cac chdt trong thdnh phdn cdng t h d c da d u y c cong bd trgn d u y c didn '^•'^, tuy nhidn, chiing tdi can khdo sdt dd ddnh gid riOng le vd dg an todn ciia dung djch sau khi pha chd trong phgm vi phdng thi nghigm. D d ddm bdo tudn thii cde quy djnh, chiing tdi da gdi mdu cho Vign Pasteur TP.HCM - Id c a quan ed ehde nang t h u nghigm tieu chi ndy, kdt qud bdo cdo d y a tren phidu trd Idi kdt qud ciia Vign Pasteur (cd mdu: n=20 ngudi).
Ghi nhgn kdt qua t h u nghigm:
- Phdng vdn tryc tidp n g u d i tham gia thii nghigm bdng bang cau hdi sau thdi gian si>
dgng.
- Thdng ke ty lg trd Idi cde cau hdi, kdt lugn vd tinh an todn cua san phdm tren n g u d i si>
dgng.
• Nghien CIFU - Ky thuat
K e t q u a v a b a n l u | n
Quy trinh vd p h u a n g phdp pha chd d u n g d j c h
Sau khi pha ehd, tien hdnh kidm tra ede chi tieu theo yeu cdu cua TCCS ( d u y c xay dyng tren quy md 100 Ift), kdt qua n h u sau:
Bang 5: Kit qua kiim nghiim cua sin pham sau khi pha chi Tieu chi kiim tra
Cam quan The tich trung binh mOt dam vj nhd nhat Do ddng ddu vd the tich:
(20 chai) Djnh tinh:
Didecyl dimethyl amoni clorid Dinh lirqmg:
Didecyl dimethyl amoni clorid
Yiu ciu khi kiim tra
Dung djch mdu xanh nhgt, co miii d$c trung, trong sudt 1 lit ± 5%
2 chai CO dO Igch ± 7,5 % so vdi the tich trung blnh va kh5ng c6 chai nao Igch qud ±15% so vdi thd tich trung binh
Duong tinh Gidi hgn:
100g/chai±5%
Kit qui Bin TP TP
Dgt Dgt D^t Dat Dgt Dat
Dgt Dat
San phdm sau khi pha chd dat ygu cdu vd cde ehi tieu kidm nghigm da dd ra, ddng thdi ket qua dmh luyng da d u y c kiem chdng Igi bang c a quan khac Id Vign Pasteur TP. Ho Chi Minh, chdng td quy trinh pha ehd d quy md dd ra la dam bao ve mgt ky thuat.
Kdt qua t h d nghiem sang loc nong do cua chat diet khuan, t h d i gian tidp xdc doi v d i kha nang tiOt khuan cua d u n g d j c h tren vi khuan E. coii
Ndng do cua chat diit khuan ddi vai khi nang tiit khuan cua dung djch
Bang 6: Kit qua ndng dp didecyl dimethyl ammoni chlorid ddi v&i khi nang diet E. eoli
Ky hieu dung dich thv nghlgm Ung vai cic ndng d$
DDAC 5%
DDAC 7%
DDAC 10%
Kha nang diet E. coii
++++
++++
+++++
Thm gian tiip xuc cua dung djch Bang 7: Kit qua thu nghiem th&i gian tiip xuc tdi uv ddi v&i kha ning diet E.coli
Ky hi$u dung dich thi' nghiem Kha nang ung vdi thai gian tiip xiic diet E.coli
DT4 ++++-»- + + + : khd nang diet khuan < 90%
+ + + + : kha nang diet khudn > 90%
+ + + + + : kha nang diet khudn > 9g%
Nghiem thdc DT3 (thdi gian tidp xiic 20 phut) vd DT4 (thdi gian tiep xiie 25 phiit) cho kdt qua diet khudn tdt nhdt (>99%). Do dd, thdi gian tidp xuc tdi u u khi s u dyng san pham Id 20 phiit.
Ket qud t h d nghiem m d rong tren nhieu Chung vi khuan
Bang 8: Ket qua thu nghiem m& ring tren nhiiu chOng vi khuan
+ + + : kha nang digt khudn < 90%
+ + + + : kha nang digt khuan 5 90%
+ + + + + : kha nang digt khudn > 99%
D y a vao bang kdt qua chiing toi nhdn thdy:
cOng thdc cd ky higu DDAC 10% (didecyl dimethyl ammoni chlorid 10,0%) cho kdt qua digt khuan tdt nhdt (ty le digt khuan > 99%). Do dd, ndng do didecyl dimethyl ammoni chlorid cdn s d dyng trong san phdm Id 10,0%.
Ti4P CHI DlTipfC HO€ -06/201*4^6 434 NAM 52)
VilthuSn thir nghlgm Bacillus subtilis
P. aeruginosa S. aureus Mycobacterium
Samonella Shigella Mycobacterium
KStquithu' nghiem sau khi tiep xic 20 phit S6 Itr^g vi khuin
con song 0 0 0 0 0 0 0
Tyle diet khuin
100%
100%
100%
100%
100%
100%
100%
• Nghien ctPU - Ky thuat
Dung djch thd nghigm ed khd ndng digt cde khudn gdy bgnh ndu trong bdng 8, sau thdi gian tidp xiie 20 phiit,
Thd nghigm tinh an todn cda sdn phdm trdn ngu^l sd dgng
Thdng kO bdn trd Idi ctia nhdng ngudi tham gia thd nghigm sau khi sd dyng sdn phdm, chiing tdi cd sd ligu nhu sau:
Bdng 9: Kit qui thu- nghiim kich img eua nhOvg ngu&i tham gia t/id nghiim
Chi tiiu dinh gii Dau ddu
Ho Nfln Ngda ngdy
Sdt Hdt hai Dau byng Nfin mda Dau mdt Sdmui Tigu chdy ChPng mgt
Ci Khing
+ + + + + + + + + + + +
(-): Khdng ghi nh$n, (+): C6 ghi nhin Khdng ghl nhgn ed bdt k^y* hign tuyng kich dng hogc edc vdn dd vd sdc khoe duyc ndu trong bang cdu hdi phdng vdn nhung ngudi thd nghigm. VI vgy, cd thd kit lugn Id sdn phdm an todn cho ngudi sd dyng trong phgm vi nghidn cdu d phdng thi nghigm.
K4t lu$n
- Sdn phdm nghign cuu dgt ygu cdu vd mgt quy trlnh, ky thu$t bdo chd, dn djnh trong quy mO phdng thi nghigm.
- Khd ndng tigt tning cOa dung djch mgnh (digt 100% vi khudn) trdn E cdi, B. subtilis, P. semglnosa, S. aureus, Mycobacterium BCG, Samonella.
Shigella trong thdi gian tidp xiic 20 phdt, d ndng dO 10% vdi ty 10 pha lodng tdi uu Id 0,5%.
- Da duyc thu nghigm vd kdt lugn an todn cho ngudi su dyng bong phgm vi phdng thi nghigm.
- Sdn xudt cdn duyc thd nghlgm d quy md Idn han, tidn hdnh cdc thd nghigm dd ddnh gid dO on djnh, td dd kdt lugn hgn dCing cCia sdn pham.
- Cdn nghign cdu them cdc sdn pham tigt tning khdc sd dgng trong bgnh vign vd tidp tgc thd nghigm them kha nang khdng ndm.
24
S u m m a r y
Infection in hospital is the most concerning of medical administrators, because it is one of the main reasons of increasing treatment time and fee, furthermore it could make serious problems or be a reason of patient death.
In the purpose of creating the new product ivrf/?
the optimal ingredients and the cheap price comparing to the imported products, in c^der to supply to the need of hospitals, to save much government cost, we do the research to manufacture the product for disinfecting medical surgery or endoscopy equipments in hospitals. The product with ingredients: Didecyl dimethyl ammonium chloride 10%, surfactant 2%, detergent and corrosion inhibitor 6,6% was produced and passed the testing of technical requiremmits in producing, showed the stmng disinfyetkin (100%) in testing on Escherichia coll ATCC 25923, Bacillus subtilis PY 79, Pseudomonas aenjgi'nosa ATCC 27853, Staph^ococcus aureus ATCC 25922 Mycobacterium BCG, Samonella. Shigella, with no report of irritation on voluntary/xrsons.
Keywords: disinfection, sterilization.
Tcii li^u tham khao 1. so y ti, Chl thj sd 06/2005/CT-BYT ngdy 29/12/2005 vd vigc vigc tdng cudng c6ng tdc chdng nhidm khudn bgnh vign;
2. SO Y ti. Quydt djnh sd 09/2006/QD-BYT ngdy 07/02/2006, ban hdnh danh myc hod chit, chd phSm digt cfin tning, digt khudn dung trong Finh vyc gia dyng vd y td duyc phdp ddng ky dd su dyng, duyc ph6p ddng ky nhung hgn chd su dyng, cdm sd dgng tgi Vigt Nam.
3. BO Y td, Quydt djnh sd 3113/1999/QE)-BYT ngdy 11/10/1999, ban hdnh phuang phdp thd dO kich ung.
4. Trdn Huu Tdm (2009), "Nghifin cdu pha ch^
thd nghigm dung djch tigt khudn tay nhanh sd dgng trong bgnh vign", Tgp chl Duoc hpc, sd 403 (11/2009), tr. 36-39
5. Trdn Hdu Tdm, Tdn NO- Quynh Nhu, Phgm Thanh Phong (2011), "Nghign edu san xudt thi>
nghigm dung djch tigt tnjng dyng cy ngi soi sO dyng trong bgnh vign". Tgp chi Y /7pc Thyc hinh, sd 762 (4/2011),tr. 13-15
6. Rutala WA. APIC guideline for selection and use of disinfectants, AJIC Am J Infect Control (1996);
24:313-42.
7. United States Pharmacopeia USP30-NF25 (2007), Disinfectants And Antiseptics, p.504.
