Drug nanocrystals: a 240 state of the art formulation strategy for preparing the poorly water-solubleQ7 241 drugs.. Controlling particle size of a poorly water-soluble drug 245 using ult
Trang 11 Pharmaceutical nanotechnology
4 Q1 Thao Truong-Dinh Tran * , Phuong Ha-Lien Tran * , Minh Ngoc Uyen Nguyen,
5 Khanh Thi My Tran, Minh Nguyet Pham, Phuc Cao Tran, Toi Van Vo
6 PharmaceuticalEngineeringLaboratory,BiomedicalEngineeringDepartment,InternationalUniversity,VietnamNationalUniversity,HoChiMinhCity,
7 VietNam
A R T I C L E I N F O
Article history:
Received 31 May 2014
Received in revised form 28 July 2014
Accepted 14 August 2014
Available online xxx
Keywords:
Nanosuspension
Sonoprecipitation method
Crystallinity
Dissolution enhancement
A B S T R A C T
The aimsof this studyare to increaseand explainthemechanismof dissolutionenhancement of isradipineusingthesonoprecipitationmethodforstablenanosuspensions.Therehavebeenstillfewof published researchesonformulationofisradipine using nanoparticleengineering.Nanosuspension systemswereprepareduponvariousfactorsincludingamplitudeandthetimelengthofultrasonication ThedissolutiontestwasperformedaccordingtotheUSPpaddlemethodinintestinalfluid(pH6.8).The crystallinestructureofdrug,themolecularinteraction,morphologyandsizeofnanosuspensionwere also investigatedto determine themechanism of dissolutionenhancement The sonoprecipitation method withuseofHPMC6 showeditspotential inenhancementofthedrugrelease rate.Stable nanosuspensionwassignificantlydependedonamplitudeandtimeofultrasonicationsincethesefactors affectedonthesizeofnanoparticles.Thesynergisticeffectsofreductionofdrugcrystallinityandparticle sizecouldincreasethedissolutionrateofisradipinebyprovidingastablenanosuspension.Thiswork maycontributetoanewstrategyforimprovementdissolutionrateofisradipine
ã2014PublishedbyElsevierB.V
11 Agrawal,2011).Therefore,oneofthemajorcurrentchallengesof
18 Liuetal.,2012;Miaoetal.,2011;MoorthiandKathiresan,2013;
19 Zhengetal.,2010)becauseultrasoundhasbeenprovedtobean
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Cohen,1997;Leroueil-LeVergeretal.,1998)andmaybedegraded
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and Tran, 2013; Tran et al., 2010) Recently, Park et al has
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(Leroueil-LeVergeretal.,1998).Theaimofthosenanoparticles
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transmis-46
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* Corresponding authors Tel.: +84 8 37244270x3328; fax: +84 8 37244271.
E-mail addresses: ttdthao@hcmiu.edu.vn (T.T.-D Tran),
thlphuong@hcmiu.edu.vn (P.H.-L Tran).
http://dx.doi.org/10.1016/j.ijpharm.2014.08.017
0378-5173/ã 2014 Published by Elsevier B.V.
Trang 250 2.Materialsandmethods
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microscopy
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Table 1
Formulation of IS suspensions.
Formulation IS
(mg) HPMC
6 (mg) HPMC 4000 (mg)
PEO N-60K (mg)
Sonication amplitude (level)
Sonication time (min)
Time [min]
0 20 40 60 80 100 120
F3 (PE O) F1 (HPMC 6) F2 (HPMC 4000) pure IS
Fig 1 Effect of polymer types (PEO, HPMC 6 or HPMC 4000) on dissolution rate of IS
at pH 6.8.
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formulations
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Time [min]
0
20
40
60
80
100
120
F4 (20 m g HPMC 6) F5 (10 m g HPMC 6) F6 (5 mg HPMC 6)
Fig 2 Effect of HPMC 6 concentrations on dissolution rate of IS at pH 6.8.
Time [min]
0
20
40
60
80
100
120
F7 (amplitude 2) F6 (amplitude 5)
Fig 3 Effect of ultrasonication amplitudes on dissolution rate of IS at pH 6.8.
Timne [min]
0
20
40
60
80
100
120
F8 (4 mins) F7 (5 mins)
Fig 4 Effect of ultrasonication time on dissolution rate of IS at pH 6.8.
Fig 5 Precipitation observation of formulation F6, F7, F8 at room temperature until
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Trang 4146 intensityofsonicwavesisdirectlyproportionaltotheamplitudeof
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dissolu-186
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IS (Hu et al., 2003; Tran et al., 2010) These results clearly
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2009;Vasconcelosetal.,2007)
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Fig 6 SEM image of pure IS (A) and TEM images of particles in formulations (B) F7; (C) F6.
Trang 5212 drugmoleculeandHPMC6thatmayaffectthedissolutionrateof
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Acknowledgement
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2-Theta
Pure IS
HPMC 6
F6
Fig 7 PXRD patterns of pure IS, HPMC 6 and freeze-dried sample of F6 formulation.
Wavelength (cm-1)
1000 2000
3000 4000
pure I S
F6
HPMC 6
Fig 8 FTIR spectra of pure IS, HPMC 6 and freeze-dried sample of F6 formulation.