C. M. Keck and R. H. Müller, Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisation, European Journal of Pharmaceutics and Biopharmaceutics, vol.62, issue.1, pp.3-16, 2006.
DOI : 10.1016/j.ejpb.2005.05.009

D. S. Kelley, P. C. Taylor, G. J. Nelson, P. C. Schmidt, A. Ferretti et al., Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men, Lipids, vol.45, issue.4, pp.317-324, 1999.
DOI : 10.1046/j.1365-3083.1996.d01-42.x

S. M. Khoo, C. J. Porter, and W. N. Charman, The formulation of Halofantrine as either non-solubilizing PEG 6000 or solubilizing lipid based solid dispersions: physical stability and absolute bioavailability assessment, Int. J. Pharm, issue.205, pp.65-78, 2000.

S. H. Klang, M. Parnas, and S. Benita, Emulsions as drug carriers -possibilities, limitations and future perspectives, Emulsions and Nanosuspensions for the Formulation of Poorly Soluble Drugs, pp.31-60, 1998.

F. M. Köhn and W. B. Schill, A new oral testosterone undecanoate formulation, World J. Urol, issue.21, pp.311-315, 2003.

A. Kuksis, Absorption of fat soluble vitamins Boca Raton, Fat Absorption, pp.65-86, 1987.

G. Kutz, Kosmetische Emulsionen und Cremes, 2001.

C. J. Porter and W. N. Charman, Intestinal lymphatic drug transport: an update, Advanced Drug Delivery Reviews, vol.50, issue.1-2, 2001.
DOI : 10.1016/S0169-409X(01)00151-X

C. J. Porter and W. N. Charman, Lipid-Based Formulations for Oral Administration, J. Recept. Signal Transduct. Res, issue.21, pp.215-257, 2001.
DOI : 10.1201/9780203908563.ch4

C. W. Pouton, Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and ???self-microemulsifying??? drug delivery systems, European Journal of Pharmaceutical Sciences, vol.11, issue.11 2, pp.93-98, 2000.
DOI : 10.1016/S0928-0987(00)00167-6

M. Radtke, Grundlegende Untersuchungen zur Arzneistoffinkorporation, -freisetzung und Struktur von SLN und NLC, 2003.

B. D. Rege, J. P. Kao, and J. E. Polli, Effects of nonionic surfactants on membrane transporters in Caco-2 cell monolayers, European Journal of Pharmaceutical Sciences, vol.16, issue.4-5, pp.237-246, 2002.
DOI : 10.1016/S0928-0987(02)00055-6

S. A. Runge, Feste Lipid-Nanopartikel (SLN) als kolloidaler Arzneistoffträger für Cyclosporin A, 1998.

W. Schmitt, Certificat of Analysis Fish oil 2261

C. Schwarz, Feste Lipid Nanopartikel: Herstellung, Charakterisierung, Arzneistoffinkorporation und -freisetzung, 1995.

D. M. Shackleford, W. A. Faassen, N. Houwing, H. Lass, G. A. Edwards et al., Contribution of Lymphatically Transported Testosterone Undecanoate to the Systemic Exposure of Testosterone after Oral Administration of Two Andriol Formulations in Conscious Lymph Duct-Cannulated Dogs, Journal of Pharmacology and Experimental Therapeutics, vol.306, issue.3, pp.925-933, 2003.
DOI : 10.1124/jpet.103.052522

A. Orklinal, lE5 rug/>« in ca« of hig/l <Itctro<tatk, TI>< m<a<· ill<tll<na in ultnpu« ~

T. Fllrti><nnot<-«l«tro<tatk, li>< ronn.tiOII of. p_.iik< port, 1<0 .tabili.ing li>< '~-'l<rn. Tru. i. ~-<iI oio=ribed rot rug, p.or

. Tl-'gs and . ~·it~-li><-p<>rt, d PVP in OOO1birul'-on: .tn>o' LIr< ,1>< ~LC~ F

J. Crplljlüj><u and T. ~lc~, ing <>lorim<try (DSC) ..d Fig. 1 <Jlo',<-.'I>< DSC grapll. Corn· F"'r<d 10 lipid O)-..... n Il S b<Iik m.t<ri... li>< p<

D. Il, S. ~. Ing, K. Dsc-~-'itll-modi, . @bullet, and . Ti><, woy'glF<M O>fl aY'1O<iliiC On 11= dif· r<.d ~ (mo<' tl><nnody1y 'tabl<) Rutirlg rul'l"< ofll><, 1< li>< tIIr«, p.1

1. Modi-''''., mnimum" 72.1'C ~I>< <oeting I<od< 10 <n'talii..tiOII in'o li>< a tmdi'''''';OII (11.1 'C). Furtl><nnot<. li>< «oond "l"<1< <Ilol'-. li>< Wmodo il ~·itII il< m<~ing poin' of 61

. Ti><-=otd<d-x, di"r.ruOII .p«trum of ,1>< b<Ilk m

J. .. __-_-_, Ils (Fig. 4) <Ilol'-. 11I< tIIr« <xp«t<d p<.la NLC

. H. Modi-''''., of li>< lipid: 16.4 (lO) rot 11I< a modi, 19.1 (20) fot 1\ ..d 1l 1 (20) ....d 14.1 (20) fot ,1>< Wmodi',cation

1. _-<-d-'muid, 1. Ir>oorponl<d-ot, D. Tipid-il, ~. ><, and !. Y. , t<o fouoo t1l.I' 11>< l<ngtll oft!>e f.tty.cid dloir" fi. f.tty >cido ~·itII. dI>in l<ngtll of CI4 10 CIS promo« .b<orptiOll 1»" ~-mp/l.ll'" uPU" (Port« >no:! 01>rmoo 1. _ioo ?. it .. bffi<1kilol if 11>< lipid" FJ««.1<d ... n""ly di,p<ru.!" po..iIll<. TI>< ,-"ioI"", in bioly';lJl>itily of 11>< 1"" q"Clo<porirI A produ"-S .ooimmu",~. ~-<r< <xplllin<d 1»" iooil-id.... ,->riaiOll in ,.n.« ",m-< bil< wU, ind«d. 1«, bil< wU. 1«, ..f<c· 'iI--< di'p"'iOll oftlt< cil, 11>< ool<g.l f>lly .cid TI>< 'rig~"«rid< <1IO«tl (0)-...... Il S _ gl~"C<"fl, pp.11-11, 2001.

C. S. Colllllin and ~. L. , po<,iIll<. 'full m..." in 11><Id lJtO'I"ld<, 111linl-'l1 11>«<

. Ioc<tll<n-'ficlo« and . .. 11><-"->-!->ili, c=<t\Hy i. pt<l""'tioo Il could b< o!IO' .I' . t1l.I' tI><r<fullli,m of d<W,r:adlooo. 1><1'01-""" cil dropl<U >no:! lOIle1 lipid f'lrOCl«. Th< ootid tipid f'lrOCl« .r< d<g1:ad<d 1»-" 10p>«<. 11>< d<j.I'lId>oo Compo<itiOll of 11>< port

!. Io-'.-i-, f'lrticl<' <n'« ,fie g", Iipa«._0 1110 ,fie port"'l< ''''. fao< ~~ , tII< >d. promot«! 1»" 11>< p< of "'.lip ElIlymaic d<j.I'lId>tioo of ,fie liplel port"'''' l<ad, ' 0 11>< fonn

. Dil«-)-fot,-fie-lipoptliil<-il, A. Rotnf-'o1<-tii<-unpl<......-',-m<ii, . Il, and .. I«1<d-fot-m, 00 ,orrounding 11>< f'lrOCl<' 1»-" ? poorty dil'iuilll< m<diId no< rotnpl<t<1y <lim ,m<1I. ing' Or>ttg< 1<m0ll-<r< 'l'pli<d in dilf<t<l\, Th< mo<! ..lld<n ot· ? ng< 1'1»

1. @bullet and 1. Ing-iom<, 11>< moll<tl lipid bl<tld i"" priot 10 OOmOj of ,fie I"Olail< Il>, llomOj.<tlil.lll"" ~'ill ~< plll« in clo«d coo>in n.... "ming .ny r< ........, lb, p.10

A. Cclou, ~. , T. P. Il, and . F>o, cOO«n fot colour· ing ,fie prodl!<t, Food colour )-<1 ZLTl in14% >no:! 0.011% food cclou, r<d ZLT1 1.1. Cily di'p"'ibl< i. Ilulel mali>. TI>< fonnullllOOII r<pt<l<t\U ?? "t<rnai,-< fot p<, bl< fot .b<orptiOll i. 11>< g ~M fl.I>-< prolll<tm ,~-.I1",·ing ",W do<>i< fonn 11>< port"'l< m...h >no:! fonnulaiOll

. .. U_-<h......, M
URL : https://hal.archives-ouvertes.fr/in2p3-00277323

_. @bullet, 0:<' or

J. and _. .. N-"-",, A (200<
URL : https://hal.archives-ouvertes.fr/in2p3-00146875

.. .. Miojoj-"., _. _. , and _. ~. , M ('_' EfIo<o or, EqJJ MoJ

.. ,-'~,...-o..., C ('_' <oU l-9

~. , _. /. Poimurya, and /. , IillI r

H. , _. , ·. Pofi«, and K. Mul~, ~I1 T«bull.,.-be;li~oan;n'_'''6i 19\1" Clutrman,000 Za\:,001). Vitamin. 'Uo<b .. ,-itamin A ..-.:1 [ .r< 1><11<, al>«i<bed in 11>< TO«?? r< quit< ? ouml><, of drull' foo ~'hich an ir.<r<a«d 0001 biOll' aitobility " r<po<t<d ~'1><0 1I><y ... admin"t<r<d in 11><, · rich food Eumf'l« ... 1«10<1«00? ..-.:1 lutIofantrl"" (Clutrman '" Port<" 1_, 1I01rn <t .1.,001, KI>oo. Pon«, 1987.

<. Ao, Ih? <am. tim. of high cornm""," inl««[-<. cYCK><porio A D<li

(. S. Roli, 1. Ctly-tnuo<<d-ih, S. Ic, ·. Rolim-1i0w, and W. Rti, 19119) ln. cornl'-""ti\". in \"~·o '100)', cy<lo<porin A n ??dmin,· l<r<d ... drull"''''''''l''utl ,u'p<n''''o (10 and inoo'f'O<"'<d inlo IOlid l'I'id. in 0001 bioo,-aitobility r<port<d foo drull, CUMy. 19\1l). In COO""'I'" Ih" liI<u,ur. dala, 11>< ""ulll of 11>< cYCK><porin A "-.. ualO~· ET Al OOug< fü<m< «.g.? tal>1=. 1"11=)" 0 lot of nt both prodoclion pro",..<.-I>om"ll",inlion 000 micro<rnullion m<1l>OO-y"td an idental produ<t IOlio:! hpio:! particl" di<· p««d m on "'1""00' di<p«<ion m<diuln. A, oi«<ril>ed in 11>< pal"'t (M~II Locb. 19%). SU, pr<par<d by hip

!. Clpod, 1:<. E'p<<<oUl' SL~' J""I"rOO from on< hiihly J>llrifIiz< m 0 0< l«, p<rl«t «)'''''1''' l''oc<. Soch 0 p<rf«t «.,-.alli .. '1N<I"'" 1"'"<5 lit· tI< room fo< 11\< it><0fl"I<aIi0n of drui'. U'ually. drui' arr it><0fl'0<"I<d 1>«...<", tl>< fonl' acio:! <1ta~"1y in !>«~-«n lipio:!IO) f«lion?. Tl>< mot< p<rl<ct d<".. 1y pa<~al tl>< «)-~tal ". 11>< f<...« drui Cln 1>< i and ~ Ouri"i 'lOfai<. 11\< l'l'id, 0< in _"'l'hou. <lu, p.0

~. Con«<tu<tltly, p<rf«t l'l'id «)-~t"l"" <tno<t"'" teod, to, 1997.

1. Ronirollal-1\aoo51n<turi-"-i-of and . Pati, po<,ibl<. T0 ach<1)' diff<""'1 mol<<raJ 0 IOlio:! lipid " mix<d ~·ith 0 Iiquio:! l'l'id (oil). Th.. bl<rol " u"d 10 prodoc< tl>< l'l'io:! part"'l" tlu< arr <tililOlid, 10 abo<!l 4<J'c Il Cln 1>< ,ummoriz<d that SL~' or< parti<l« prodlJC<d from 0 IOlio:!l'l'io:! only rol ~LC'" arr part

!. Clpaci, Thi< of 11>< part"'l< motrix i Clpaci1y 000 minimizi"i 0< ,-oidi"i drui "'J'lIll"'" duritli '1""1:< wc Ba«d on 1I><it hPOl'hil'" <!tara<I«. SL~' 000 ~LC'" ha,.. onll' 0 Itmital loooli"i Clpaci1y fo< h.,-drophili< drui'. Th Mt 0 prol>l<m m CI" of hiihll' po1<"t h)-drophil'" drui EPO: 11><)-' <an 1>< IOlubiliz<d m 11>< m<ltal lipio:! motrix u""i .macta"t mixt 000 diil)--oerid« l'''''nI m tl>< l'l'io:! 0")"-0)' «.i.? Im~·itot 900) 110 Mt ach",-abl< ~·i1l\ th.. 'ind of lipio:!lUoopart, drui" tfOf"fonn<d 10 0 mot< lip"l'hil"'. inlOlubl<

«. I. <ly-lo-lq%-i<-o<hi, . I«-sl~·, and . ~lc, Z<n< of abo<!t JJ% fonnuw<d .. diminadia«lura_acid ra_acid <onlUP1< ~·ith palmioc acio:! .1..rie acio:! (Olbrich M~II1« <an 1>< mal!< from 11>< <ooluPI<d drui onty 0< IOlio:! Ilpio:!. <an 1>< additio!wly admtX<d 10 fonn 0 mixal mallix of LOC'" 000 lipio:! rROOUCTIOI" 01" UR >CALE Th< prodUoction m<ll>o<l of f"'t <110",< for 11>< th«< t)'p<. of l'I'id I\II\opart 1'>om"ll",inoon. In <a« of SL~·. 11>< drui i. di<· 101\"<01 0< di<p<r«d m 11\< m<ll of 0 IOlio:! lipid. 'Yl'i<>lly ol'l'fO"itnll<I)-' l-IO'C _ ,.. tl>< lipio:!'. m<ltini point. In <a« of ~LC"'. 11>< drui .. di<lOh"<ol in 0 m<ll<d bl<OO of 0 IOlio:! l'l'io:! ~·i1l\ 0 I",uid lipid (oil). 'Pm .Iiihtty 01>0,.. tl>< m<tl"'i point of 11>< lipio:! bl<OO. LOC'" I\II\opart"'l" .< <on-.nonty l"oolJC<d" room 1<, 11>< "'"t pro<! Uoction ,1<1'. tl>< à1.Ji-rotl

«. F. Ff,,,-"-'u and . .. @bullet-t, Il<"ization J'fOC«'. it " "'romm<r.led 10 u" di<p<l diffu''''i. <I<e- 1ll' .taI>ilizini. 10,· mol«ular ~-<iiht .urfoctanu ('.i.? lOdiLltn _l'~ulf Th<)' diffu" ''''l' f..t i"1O "~.Iy fotm<d in1<rfmoll dr"l'I<.. <mcl"'tll' minimiz"'i .Ub«qu.<fil ro'-«>« ph, 1SI). SI",i< 'ab~ lization .. I.tl< 0< 1", tmpa;ml by 11>< Jl

«. A. Ol<y, ur<-<onIroIl<d hiih-J'f«'u", 1'>om"ll",iHrIl>« from tl>< p..too- Pl' typ< (ArV Gallim. M'V D<uu<ltl..-.l GI>"i>II< (mi<rolluio:!iLll, 0< from tl>< j<l prin<'l'I?? Mi<rofluio:!iHr

. M. ·lon, \. Us, . Nanol-'altl<u-'m, D. Al, . Ug-[-)-eu-'uv-ij97 et al., Il-.:I ~LC..z .. ai"'" t),I'''''11)' al>o<ll l'C _ ,.. 11>< m<lti"1l fIO"'l of 11>< l'l'id l'ha« aro:l room l<mfl'<'" 1"'" fOf LOC..z 1" pri"'''l'~ fOf SL~·..-.:I ~LC..z prodoctioo, on< 1>o""'ll<"",tion c)'c~ al Joo!lM .. ,ufflci<flt 10 y;'te1 a 1>o<0ilwa

. Tyl-'icai-h, fIO<t<d in 11>< litera· 1"'" are 100 bar aro:l ul' to tltr« hom"ll<fliz.alion c)'d"?. Th< IWO aOditional C)'d.. leao:IlO a furù><, .Iight ,edoctioo '" 11>< l""icl" .iz" to _ima"l)' "0 nm ..-.:1 a tam:lw"'ll of 11>< ~·idIh of 11>< dizuiblltion ("'doction '" 11>< fIOl)'dizfl"'<ity o..l<x of fIl>o<on, PCS). Ilow

1. Il-ha<-to, 1. , ~. , and ~. , 1O 11>< total drull ad<l<d. Il 'l''<<f... 1>ow m..)' J'<"'<fIl of drull are "'clL>d<Il '" th< l''mel''? ..-.:I1>ow m..y J'<"'<fIl of rr.. drulla'" ,tilll""«flt '" th< dizfl"'<ion m<dium LotJJf'g oepadJy 10 th< J'<=lIi< of drull i10 th< lipid10 th< total ~-<ight of 11>< l'l'Odic fIlw' (i.<.,lil'Od. drull)· To IlUm< a 10% lil'id lU'ion (i.<., 10% l'l'id, al>o<ll 1% In th~ Ca«" th< l''rtie~ mao, .. <qu~-al<nt 10 IO%, th< particl< mao If th< drull had a lotJJ"g _dJy of 10%, :I!9% ~-_) def....d .. 11>< ,um of lil'id..-.:l drull ( ? 100%)mc~ dizfl"'<ion E.rr_"" _ff1"'bUÙ' in th< il

!. ~. /-yofth<-lil-'id-partiel«-th<m. and . Ilow-m..-y-j-'<, 10 th< total lil'Odic m... of th< parocl« Th< laod",city d<p<M' on th<ILlbihty of th< drull '" th< ",Iid lil'Od ('" ca« of SL~'l Of th< lipid b~oo ('" cao< of ~LC..z) In ca .. of LOC' lUicl«, th< IoaJ"g <apadty i. d<I«mtro<d from 11>< of th< mol<cutal fraction, '" th< coojupl< «.ll., drullaOO coojui=d fany acid) Exampl« of laodinll oep_ll. "'fIO<I<d fOf SL~' are 1% fOf p«dr.i",lon< (Sch~-arz, 19\11), 10% fOf "1ta<ai .. (Sch~-.,. ?? 19\11), aOO ,0% fOf <)ü"j>O<'ir. ,\ by Ru"S< (R U"ll<, 19\II!), aOO1% for <)"<lo>5j>O<'ir. ,\ by RadIl;< (RadIl;<,00)). 1" cao< of

~. Blum and M. .. M~ii<r@bullet@bullet, ul' 10 JO% can 1>< ><h GaMa, 199\1) V'-hat are th< m<<ha"~m< of ~ it>ro<fIOOIlion Th<r< a Th< _je>< ~-O<I: ha< 1>«" <lot>< by 11>< 19\II!). Baoicall)', th<r< are tltr«, fIO<"tion moO<tl Ilom"ll<ro<l' m.,rlx of ",lOI ",IUlion Co«>-.h<1I model ~·ith drull <nrich<d '" th< .h<1I (. drull«>ri<l><d .h<II) C.""...h<1I moO<l ~·ith drull <nri<h<d '" th< rot< ( . drull«>ri<l><d <0"')

. Lu, Iid lipid mm <nrich<d in th< .h<II. 70.. <a" 1>< <>pwr.<d by a lil'O:! l"""l'iation m«hani.m occurri"ll duritlll pamc~ prodoction. Ml<'ll<nizOlion, th<r< .. a mixt"'" of drull roll'l'id", <><h drap~t Il .. th<fl I><"'ll 0001«1. D<p<OOUlIl on th< TX "'Iubility dÙlgram, th< l'l'id ca" l""''l'ia", ..ri;', than th< drull to form a drull-fr« cO« or" I<..t HO« ~·ith r<doc<d dnJll ""n1<flt (TX dÙlgram' a lwo..:l"""n.ional ll"'I'hicai "'pr«<fllatlon, ~·i1hI1<m). R~h'"ll th< <tit«oc 1<rnJ Exampl« are ""<fIl)'nl< QI 0 SL~ Th<, of th< t<ooaric l'ha«1y '" th< 0ll1<r .h<1I of th< lAFM) (OUlll

T. .. Th<-incrn«d-"...., Iubilrty fOf m..y dnJll' '" th< OU"" l'ha« (.urf><taltl ",1"· tion) ., <I<\ ...d 1<m)'< Coolinll of th< oi~w"<r FlGUlE 1 -'-I 139UrnDlI' ET Al "üU, II" .. do R Of

». .. >ill, J>Ol<"ti

. Somimiwo-'üfi1ooo1i~, 1(~ttl< OEÙlion

A. and !. .. 11><-l-'y<lo<porin-'\-lu-th, <On-- lra11 10. i" bioo"oil>l>itity t<poned for a "umb« of drull'.1»' 11>< 1ci"'1"" of 11>< < 11>< bioo"oil>l>tiit)' of danazol ""uld 1>< inaeo«d from 1 10 !:1% b)' ""o,f<l'li"ll m< drulllO a IU CUr.d)'. 19\11). Th< "' aIOO' fo< 11>< 10... bioo"aitab'lrty of l')'<lo<porin, 11>< pl' '",inl..tinal fLuid. Il i, kMwo th., IUOOctyl1" aggr<pl"" <an 'lGUo.E' fil

. Sl~-'d..-p<n<lo<porin, ". .. M~ll<, . M~ii«, R. O. Ru-"-il<, I. Th~ et al., Il<, 19\II!) A. m"'tion<d lUM<mutlioo ",doc« th. dNg wiubilay in 11>< "' 1"""' " f'l\>«, drull tri«'" f<I'Irtition inlO Il>< l'l'id lding 10 <Mch! in 11>< J"'lk~ .1><11 in ca« th. J'lrticl< co« oIreodl' Itl""d to wlidify (Fill"" lI. Soch f""licl«.r< <rown 10 l<od 10 ? !>U 19\11) In th. ca« of th. onI cyclo><porin'\ f, 01 ..phroloxi< 1<,..,1 ?. In ca« of o<h« "1'l'liation., it miih' Il<, 1999.

. C. L\a-il< and . M~, .d by ,atyi"ll Ù\< pro<!IJoctll 11>< f'lrtiçl< pro M<!u><rt, IWIl) Soch roro:litiom"", 10"" pro<!IJoction

1. .. Ion< and . 19\16, 11>< IIi"ll, 0 ,uP<' I.oluration..-.:l 'U!>«qLJ.<fil drulll""cip'lItion.d 1»' lh.. mod<l (zur M~"I M<hr.<r!, 19\II!) rN FLlrÙI<rmo«, it might 1>< tlu< tl>< d"",lutioo r'l< of <y<lo<pori" A frorn tl><, <t>1< n. Ml a< high a< frorn 11>< hl'id lur'II,..ti

<. .. Th, . <y<lo<porin, and 1. Wa<, 11>< 001I of1l>< SL~' a< ir.:!i00 in in ,-itro «1<....100... (Ru"ll', IWIl) ln 'UIn, drull 1UOO. fonwl>tioo _ < I I fo< pooriy ",Iubl< drull', do Ml "-0<'< in '"Y <a«. Fo<. "um!><r of drull', it, 10 1>< I><,...r~ ci.. to""" lipoli p««rtt durinll tl>< >b<otption J>ro«<'. Thi oel<ril>i"ll ÙI' J'O"I~" .ff.ct of lipid. 00 0001 drull .!><o<ptioo, p.0

C. .. @bullet-liolrn, Th<<<fo<<, ÙI' r"'l <!>ok, Porter ...1.? 1_Il might 1>< drull IUOO<ry'w., bIll lipid _rti<~. ... 11>< .... "ti.. !»<k up fonnutalioo, 1997.

$. Mecilani, . \1, . Oral, and . Eniiar-;-cement-tti<r<, It leao:I 10'" >b<orp!ioot.ro:! ilio todoclbl< bi<>ly.i~ >bility (Iinl< """'00" in bi<>lYoitabilily) TI>«< m«lWt"m. ? i"'<r>I

. Ctly-r<~, Ml .p.cifL< fo< lipid lU

!. Th-"->d, . Th<, . Qed, D. Sl~-',-u-'i-a, and E. , :1 fa! <t.ol... ron.i_ .. y.. id fo< ÙI' hl'id tunOj>.olli<l... Tl>< low Y>ri.olioo in bi<>lY.i~ >bility ol>«r\'«1 "·ith <y<lo<porin A· Optonoll<'0001 mi<ro<mul<ioo (Ru"Il',IWIl) Il i< koown th 19I!7). Th<!>o<Iy >b«i<!>'I1I>< f.ol, r< lipidoch a< yia· 1>< <Xpl.....d ma« "'«LH""11y by 11>< ,100'" ptrfonna! by W. Chlormon..-.:l <0- "-0<\, 1991.

1. M. Uln, D. .. <ii, and . Oo-fonn, in 11>< llUI ~dinll 10 tl>< fro:! dill~"«rid« 00 11>< .urf"" of tl>< lipid drofIl<u a: ",Iid lipid p"oc Durinll tl>< oet><lun<flt..-.:l mic<l~ fonninll proc«&, 11>< drull d..",II'OO in tl>< lipid" 1.1 Solubili""ioo .. ? w.l~koown pri"",pl. fo< "'Iubility ..wn«m<nt in plu<, 11.. ·· In 11>< 'U!>«q

A. Illin@bullet, iÙI of tl>< f.olty ><id <Ja.n. ur tl>< primo'Y pta.,. of >b<orp!ioo. F.tty ><id GI! <!aUI. J"û"l"l< Iy"l'hloti< >I>!ofption, C1IlIln'aM Th" .. of in1<",1 fo< drull' ,och a< 1<'1

1. I~ and . W><le<, « _ « 1 Ùlrough 11>< llUI nll _ pa< , l)mplu<'" >b<o<ptioo .,-oid, th" rt<'ll_pa<. m<taI>oli<m '" ? <<ri.." oegr«..-.:I """ 1>< u<al 10 i""", tl>< 0001 >I>!<Ifl>tioo of 1<.10'1«I<f<In< uOO« 1<. A rom""r",.1 fonnutaoon "'plo""'ll th.. <oooept" Aro:I<iol' ""p'ul« "·iÙl 1..10'1«, 1< d..",~..d in o~i< ..,id (SIt><'~fool <t .1.,00)). O~'" ><id a<. GI! f.olly .cid il ioeolly .uil<d a< <ril rompoot>:! in <'l"ul< ?. Th< b".Y.il>bility of I<'ItO'lI<fOO

U. O<p>on, . T. Tt><-'''l-', and 1. Tlu<, Aro:I<iol T<'ItOCllp<' "-.« IlIllocl><d Il)' tl>< < 1>< .tor<d >t room t.l><"", tl>< -rt<'llll], to 1>< 'tor<d I><low !'C. Aro:I<iol T<lto<'l'" rontom ? b _ of 01<1< .cio:! _ <..lOf <ril (whi<ll m.;or rom tl>< GI! f,"y .cio:! ri<""I"'" .cio:!) a< <ril <""lI"""'I..-.:I >dditiO<»lIy' .ur· f''''''"1 tallroll~"olFCC (-propy~"" ll~"ooi moootae) (S"cl:~fotd.I<ifyinll drull oel~, Th. IlYoitabilily r<J'O'l<d i< >l>oot ,.!! " O.!II% (SIt><'~fotd ...1.SEDDS) (Chlonn... <t .... 199" POOIOO, p.0

. M. Ff, of al>o<ll ,10 Ml ( . 0.21~m). Solubiliz.alion CO" ta\;< pla'ty dLJ< 10 11>< la'll' ,un",. or.. ofl1>< ;>arti<l« ln cal< ? ?"w" deWadalion, fo< prolool:.d «1....)?? fraction of 11>< 11« CO" Il< .Ulliliz<d ~·ith

1. Il-ro<ltcl-il< and . Lipid-flgule-'_-_, I.own tlu< 10 «>m< <xt<"' 11><

_. 199i-! and K. Ollrich, 11>< 1)1'< of <tll>iliur .ff"", 11>< 'I\Z)-" m.,i< deWadalion,bilintion of 11>< lipO:l ;>art"'''' ~·ith ? mlxlur< of <Odium <!>ola, Otbrich. M<!u><rt, vol.001, issue.11

<. Itpa«, 1. .. , and O. , M~II«, 1999) Th< u'" of high mo~'" ulor ~-<ighl <tll>iliz«< ,och .. Poloxam<r 407~, 10. '1«i< hirodran"" of 11>< an<l>o<i"1: of 11>< <00>1'1<>:, mu. d<tayi"1: 11>< I1: mlxll"« of deWadalion, teratinl: ..-.:1 d<w>dalion d<la)"itll: .abili..... (Otll<i<h '" M~tl«, 1999.

". Til and !. , 1: l"ll" «>~ _h Mt« qu.alrty of 11>< 1"00"" ~·ith «ganllO ??ImI'" meon J'lrtk~ .i l . and it5 !>o<lY (widIh of 11>< .i.. d"trib<ltion) Bal' " ad\-.nal:' .. thal high-pr«,«lI"''' iMUi1r)' fo< 11>< 1"oo""ion of <mut<ion. for J'lf<n, ilalion ... pro<!OCOO" t<cl\niqLJ< ~·id<ty u«<l food pro<!""ion, ~.1><<< !>o""'I

_. , .. .. Tyi-'i<ai-ma<h., ·. 11><-a, A. Uh, and ·. .. , fot tal>-"",I< prodoction _ th< Micron L\B 4<) (bal<h .il<: ,0-40 mL,\PV D<uu<htaM GI>"i>Il) andtin Cl (balch .," 7 mL to 1 l,capa«ty_ tin E""'f'<) In ca« ofl-..y <>:l'''''~'' drull' ot if1l><rc ... hm· ital ,u1'l'Iy «.ll., n<w ch<mi<aI "'Hti..), it il f,-otaI>l< to rNoc< the balch .il< (ICalinll down ''''l''biltty). Bal<h .ize rNoction con 1>< do!>< by utin E""'I'<) Th< bateh mlum< il O.~J.' mL A f, ion of th< Mi<ron L\B 4<). Il Ul« 11>< <am< h

T. Ion and .. .. Coowl, :I ll<Om<"'y of 11>< hom"ll

.. Th<-ma<h, Il ~·ith 4<) ml <a<h .rc rcqu<!<d). 1" ca .. of 11>< coot0 , ion, 11>< 1>omoll"'iZllion tower.oo 11>< two prodlJCl cootlu,1'fI<d ~·ith I<mfl'<"lur< co", Irol jacbu. 1" 1I>eot)', on< could "'tarj:< 11>< prodlJCl COOl OOll""'lly 00< dc,igned 10 N" tarj:<r mlume< in COOlxt ICaI"'ll ul' 'l<fl ~·ith. min.mum bateh .ize of, 'll ..-.:1 ? muArV D<uu<htand GI>"i>Il). Th< L\B 60 ha<. hom"ll",izotio" cal""it)' of 60 Uh Th< two prodoct conta 10 pr<fI"< 11>< pt<-<twl.ion in it Fot th< production of, um of 10 'li ~-.. a<h....·ed u,inll th< L\B 60ll bateh, th< pt<-<twllion" fI&l«<l throllgh the hom"ll",izotioo un'l, and 11><" it ci"",I.,.. bac. 10 11>< f«dinll coot""",. Il ... contin""", l>omo:Ig"'''alion pro

1. Il-can and T. Ur<-tha,.., 1\ min 10ti<tically-99.'/% of 11>< drofIl<Il ha,.. 1"'«<1 11>< 1>omoll",iZllion ,-al,.. al a.l oncc (l<'.-iton '" rallanlch, 19\9, M~II<" Wil.inll

. Min-10, ur< that 99.9% of th< dr"l'i«' ha'... 1"'«<1 11>< 1>omoll",iZllion Pl' al l<Olt

. Th<rcfore, <. .. Th<l«, . Ulu-olna, _. .. Th<r<, . H. Ir et al., ,er, il ~·ill 1>< fed bac.< from 11>< ..roM cootvity via ? teure-controlled lUI>< to 11>< fI 11>< «co<>:! 1>omollI, t~-o 1>omoll",iZllion cycl.. al \00 bar.rc fully .uff";"'l 10 y"ld. rc",~"1y moood~p«« prodoc~ 11>< total l>omo:Ig<n"ation t.m< fot 10 "ll .. only ,0 min (10 min 1'" cycl<) A?? Ireody m"'tion<d, fot otally '_"t<r<d lipid _.'" on< ''''lll< hom"ll",izotioo cycl< il coo.i_ 10 1>< .ulf"'''nt ln tlW Cal<, it dot Ml mal:uny diff ,60ot nOnm Th< L\B 60 un" n. d..ign<d fot. pharma<cutical coml''n ,-. thal .. ~·hy it ca 1>< u«<l in. GMr _. fot clinical batch 1"oduction. A, JIOinted 0111 _ ,.., 11>< l>omo:Ig<n"ation.d ~·ith largc--<eal< tYl'ical1y I><TIer than ~·ith th< 1. raI rea<on. fot thfer ofti>< proc«' from ??maller capa«ty mach .... to. larger capacity of th< idcntical ot .imital ll<om<uy of 11>< l>omo:Ig<n"ation v I<adinll 10 1«. fLoctu.ation in 11>< a<nlal l>omo:Ig<n"ation pr«'ur<. Th< L\B 4<) ha< onl)-' on< plunll<c. 1I><rcfore, th< fI'«'ur< """d. 10 bIliO:l up, the f"'l .maIl fraction of th< 1"c-- <twllioo .. 1«. cff";"'tly hom"ll<nized than th<inll ~·ith thr« plunll.....moothinll th< fI'«.urc fLlJClu.alion prof.l< Furth<rnlOrc, 11>< COOlO}l of th< talller can 1>< ool<rN "lui1'fl<d ~·ith 1>< ool<rN _bic-wall<d fot t, 11>< f«dur< conIroI Utl<! fotioo Utl<! it«lf Allo, ail rcquir<d lUl>«..-.:I <ontaiur< control with. t<mfl'<"tur< controllinll l''uid. In .ddition, ù>«< l>omo:IJl<n".... _ <qu,1'fI<d ~·ith IWO hom"ll th< fI"t hom"ll1y high l ....tic <I><fJlj-'. Tl>N ,urf.cc might tIO! )"1 1>< fully co,-.rcd ~·ith\« al on< tenth of th< fI'«.ur< of th< f"'l ,-.h.. , <.ll., \00 bar fo< th< f"'l ,-.h.. and \0 bar fot th< «co<>:! ,-.h

I. , ~. Th<-u, @. G. Of, and . Uli-prodljcl-conta..., ty of 1\0 l"h (_1\0 "li) Th< pt<-<twllion .. fl'<l'""'d in tarj:er fI'l"Iuct coot. and h"""'ll<n"er.r< 1>100<1< from m.,.rial of pharma<cuticalll"dc. Th< prodlJCl cootai""" can 1>< lt<ril"ed by .!locl.Yinll' fI'<I'''''''ion of the pr<-<twllion ur.l<, l""'<e"'.. i " il fIOl"bl<. Th<y al", ha'... the f<alur.. of deln'"ll·i"1'tacc «(Ir)..-.:I «<riI"atioo-,"1'iac< (Sir). Fot th< prodoctioo,1I>< l'I'id con 1>< _lied in 11>< f<edinll cont,"cr Surf, idinll'teril< ~-.,., of SO'C, ~·hich

. Lioo-fi-'oc-"-@bullet, . Th, 1. G. Zalioo-cycl<-with, and \. \. Lin, ny of fI"l"IlJClion lcod?? Ilo 10 ? '''''y low microbiol"llical load. Fot otal admitl"motioo, on< hom"ll, Th< product .. coll<ctcd in th< ..roM prodoct con"' .... , ..-.:1 cool<d in ? conIroIl<d ~-O). UMer lt.mno:. A balch.il< of ._t half. too I-W, "-..VOIOW ET Al

1. Clin, J. In-opl-'f-",, and . Ho, 'll<nization tim< with 11>< G...I., 1.1. Fo< many prodoct<

. .. Typai-bal<h, Th~ ny of prodoction n. u«<l by 11>< company "Ch<ClR)-in B<riin to prodoc< 11>< f"'l ta'll<-""'~ balch of ~lC'" fo< oo<m<l'" indu,1t)' 10 f<ali", 11>< f"'t oo<m<oc ~lC'" prodOCIl (M~tl«, oro:! Sdlw-ab<, p.70

". Fo<, ta'll« <aI«, an A,"«tin EIWI ..F~x C1000 (A,"«tin E""'I"') 0< 0 Ra

1. <. Clin, <<ty io 1,00012,000 Uh al 11>< 10..- pt«'ur<d fo< iol'id _"iç~ prodoction ln Ihi. <aI<, it ~ no! ...,..b~ any mot< 10 J"<I"f< 0 '·ton balch in 0 diooontinL>O<l' ny, i.<., P«pari"ll 11>< ~utoion in 0 oontain«. Th<!>eIt <xchanll< ti Of< too loolllliyittll0 100 high I<~""uf<!>urd<n on 11>< oct~ Fo< production lit>« of th, 0< drull)

«. Tllnlltallil and . Wittl«thur, Th< hom"ll",iZ«! prodOCl """d, 10 1>< 000100' 11>< =l'<<''tur<oonlfOllOO oont...... w'ili Ih<n 1>< r<fIlaoed by 0 1><ot =olunll'" 10 f<mo,.. al I..-t tnO<l of'h< h<al. Fillur< 6 .how. 0 oe.illn fo< ,och on, Of< mo« <ff<cti,.. in dio· p«<i"IlOrol mof< '''l'h..tal<d f<gaNinll 11><~ f"",ur« to <<Jn

. Lfol-th<-pro, A. 0 ""ult, 11>< product qLalrt)-· ~ in Il

1. , W. 'h<n-moyittll-to-ta-'ll«, . Production, . Of, . Oral et al., <an 1>< u<al .. on 0001 OOull< fonn, f<J'O"<d (M~I,",« al., 19\11) Uo.uOd doug< fonn. miiht 1>< <oo,..,""t fo< ""rWn llfO'lP' of l""'nll «.ll., <hil<!r<n _ <to<,ty 11 <hoi« fo< d<liY«y Of< dry fonm, tllb"'., ""l'oul«, 0< f..t..:liooolyittil drull d<1~"«y ')-<1 Of< 0100 "''''1'100. p<I~1I w·itl\ I><<n produ«d by pittto _ M~II« (1_) Th< oq Sl~' di.p«<"" w-.. u«<l .. w-«tinll 'Il"" in th< pr0- duction J"O"«' of1l>< »<1, FDDS) il< th< 0001 <oyi1y. In .on.. <oontri«~I<ty ond W'ithollt Of '"«Y litll< 'Ill:"" ption. Soch »<1"" ClIn 1>< foIlal ittto ltalU 1l<loti <on"",..<d 10 'aIll<lI (?.mita, 10 »<1~I.çonwn"'ll ta/>. 1<11 .och .. B<loc ZOK')

1. !. Sl~tao and . Di, M~I 19\II!) orol 11>< ol>tlo ined l'''wd<< _ 10 th< ubl<tti"ll I<d'lIOlogy) (M~I A, m",tioo<d _''', w'h<n prodocittll 0001 doug< fonm,1I>< Ioodinll <

1. <. Drull-do« and {. , <ory 10 prodlJ« »<11eu 0< tallieu miiht 1<0<1 10 an wU<'''I''· obI< larg< I"Olum<. In ,och <a«<, it miiht 1>< """,id««! 10 prodlJ« 0 'l',.y..:lried l'''wd<< fo< oooIodmlMIration, Il, issue.1

(. @bullet, _. @bullet@bullet-iooç_, and . Il, _(obi

F. Amt, . ~. Th<-adh«i,..-j-'tam, and . Bqui, 'l'«'i« of lipid _artic"" cootd 1>< <xploaal fo, d<1~.. ,)' 10 ÙI< tnO<llh c"'ity. Ir\10 ,LJOCl\ an FDDS ~'oold 1>< I)'ophilizinll ÙI< lipO:! n"""f"rticl< ,u'1'<",ioo UM<r additioo of ~<c' ti,.. all<rta ,och B

. Mloij, w proooc" to th< ma_ i. m'<linll "'llula. tO<)' "'quir<m..", not ooly with "'i"d to .xcipi.." bIlt ail() qwolifLcatioo and ,'alidatioo of prodoction li

O. Il, . Fda-sumo, and . M. _iti, ,d in prOOOCll on th< pharma<.utical maMI. 10 th< tatt<r cal<, th<,d in th<i, commooly 'l'l'Ii.d, "'llulatOOly ac«ptI"'tioo?. If d"tioctly high<' c""".m"'tioo. a", uO«1, a limit<d toxicity 'IUdy millht 1>< ""«''''y to pro,.. th< .. f<ly of th< .xcipi.m in thi. c""""I"'tioo. Ali lipid., .urractaoll, and "abili<11'11, aM tabl<lI cao lle fully Hploit<d f"" th< prodoction of<", .ioo?. TI><", i. d<f'O'I.ly no ~ck of acc.pt.d .xcipi"lI. 10 _itioo, ail lipid.,urractaoll, aM pol u",d in food ioou"'y can b?? mpIO)-..d. 1I0w<l'<r, th<y "".d a "'lli'l"'tioo fo, pharma«utical PW'flO«'. Or.< cao r<f<r to ÙI< toxicity dall coll«l.d f T0 ,um up, a rich lao<ly of .xcipiIlipid 1U"'l"~icl<l AMth<, imJ>O<llol poilu i. ÙI< qwolifl<atioo of prodoctioo i"". within th< jl< TI>< prodoctioo lial to 1>< mad< 001 of mal.tilis aM comJ'O'lM' allowinlla q.alifl<atioo of th< prodoctioo li Ail() ..ch rompouM of ÙI< li 1- 'f"d in acad<mic, xampl<, a clinical balch prodoction UM i. ,'ailabl. r-1~1l<" Diolll<rabli.h<d and H"tioll in th< jtlarma<<utical iooU'I'Y. TI>< ~ulatO<)' acc.pl.d prodoctioo i"". f"" .mulsioo. can 1>< u, p.0, 2010.

. I><cau, ay Th<r<fOf<, it i. »O<,ibl. to u'" th< li"", of par<01.,.1 <mul· "00' f"" th< prodoctioo of lipid J'Orncl< ,u,)'<n.ioo?. Th< mil' "d"'dyaollll'--i. thot a «rtaio min""um balch " .. ~·iII lle "'quir<d, ~·hich i. 'l'\'=itml<lyhalfa ton CONCLUSION AND rERSrEOIVES Th< tht« ditf<r<m 'l"l'" of lipO:! n

. Ailability-lipol<-prodoctioo-facilrti« and . Il, 1 oral doui' fonn ?. Lipid IUOOf'Irncl<' fulfoll «1 pr<utalion. Soch pr<r<qU 0051 prodoclion, clin-.:1 aC<<p1al "alu. of <xetpi<rttl. In COO!nll to Iipo- 1Om«, th<y Mt ooly a 10,· 0051 ','I<m bill ?0???o ph,·.ically mOf< "abl?. I romm<rcial .xplortalioo .. th. .xclu,iYity of th. ,'ariou. lipid partiel. t«hool"ll"" th<y ar< 1.d pIl<n by p>t<m ai'\'licalioo, in th< majo' COllOW,. By acqu"itioo of ÙI< SL1<' t<choolOjly by s,)..rharmo nc in 1999 th< t<ehoolOjly of SL1<' hao Th< 005m<tiC produ"" l''''Y<d th< f'Bibility of 1<LC' prod"", in Il'''''aI. Allo larg<--lCaI< prodoctioo 1..... ~.<r. «tabl"l>ed f"" ÙI«< prod, l<ChoolOjly of 1<LC" .. m<an~·hil. pr«<nt 00 th< 005m<tiC m.....l in mot< thoo ,0 prodOCtl ~·otId ~·id< (M~II<r <1 al. indu,rty ('.ll., R~1er G,mll, ~·w,·.rimpler.d<), ~·hich <an a!Jo 1>< uO«1 1<0\"<m"" ,007. th< US pharma<<utical cotwid< .xclu,i,.. righa f"" th< 1<LC' t<choolOjly frorn rharm...,11O 1W'n 1<LC" inlO pharm.. c<utical producu. Th< futur< ~·ill .how if thful ACKI"OWlEDGMENT Th" ~.ot1< ~'B ,uPl""'1<d by Gawot1< of th< EU l'roj<ct "TowaN' a E""'f'<an l'hD in Ad,'....,al Orull D<liv<ry: Mari< curi< COO1ta<t MEST CT ·,()().l-1<).<99', p.p in th<

_. _@bullet@bullet-'in-'.., -. @bullet>i~, and I. , ?. ??l i, 2000.

. .. D-',-;-@bullet, J. L_-_-u-(-}k, @. ". Mi, A. F. .-"-i.-'........., _. _imj_ et al., 1< '_'1, V (2OOOo1, ft.'" L _ ._J'l.'~"I-I

,. .. @bullet and (. '. 1<, _'1'-'. e.111 Ai, E ?, 20001.

~. , H. A. 1<..-_-'".., and .. _. _~, A. 0;'1
URL : https://hal.archives-ouvertes.fr/ujm-00617603

C. .. Ol_, D.n<1_ or
URL : https://hal.archives-ouvertes.fr/in2p3-00319758

C. Ol_, A. .. -",, and . _. Loc-!-_-_-m,, L (lOO"I

A. Ahljn-io, _. , and C. J. , JI?

M. Curriculum-vitae-muchow, . P. Nationality-in-mainz-prof, and . Maincent, nd part of the pre-registration year: Dr st part of the pre-registration year: Faculté de Pharmacie, PhD studies, Prof. Rainer H. Müller, p.148, 1974.

M. Muchow, P. Maincent, R. H. Müller, and . C. Keck, Production and characterisation of testosterone undecanoate-loaded NLC for oral bioavailability enhancement, Development and Industrial Pharmacy (Drug Development and Industrial Pharmacy, 2009.

M. Muchow, P. Maincent, R. H. Müller, and . C. Keck, Testosterone undecanoate ??? increase of oral bioavailability by nanostructured lipid carriers (NLC), journal of Pharmaceutical Technology and Drug Research, vol.2, issue.1, 2009.
DOI : 10.7243/2050-120X-2-4

URL : https://hal.archives-ouvertes.fr/hal-01272752

M. Muchow, P. Maincent, and R. H. Müller, Lipid Nanoparticles with a Solid Matrix, pp.1-12, 2008.

S. B. Zirar, A. Astier, M. Muchow, and S. Gibaud, Comparison of nanosuspensions and hydroxypropyl-??-cyclodextrin complex of melarsoprol: Pharmacokinetics and tissue distribution in mice, European Journal of Pharmaceutics and Biopharmaceutics, vol.70, issue.2, pp.649-656, 2008.
DOI : 10.1016/j.ejpb.2008.05.012

URL : https://hal.archives-ouvertes.fr/hal-00399636

M. Muchow, N. Despatova, E. I. Schmitz, and R. H. Müller, Nanostructured Lipid Carriers (NLC) Containing Fish Oil as Food Supplement, 5th World Meeting on Pharmaceutics, pp.27-30, 2006.

A. 1. Muchow, M. Maincent, P. Müller, R. H. Keck, and C. M. , Testosterone undecanoate: Oral bioavailability enhancement by lipid nanoparticles, Annual meeting of Deutsche Pharmazeutische Gesellschaft, 2009.

M. Muchow, P. Maincent, and R. H. Müller, Testosterone and testosterone undecanoate ? increased oral bioavailability by nanocarriers, Pre-Satellite Meeting of the Pharmaceutical Sciences Fair & Exhibition, 2009.

M. Muchow, A. Sapin, S. Kobierski, P. Maincent, and R. H. Müller, In Vivo Evaluation of Different Nanostructured Lipid Carriers for Enhanced Oral Testosterone Delivery, AAPS), 2008.

M. Muchow, A. Sapin, S. Kobierski, P. Maincent, and R. H. Müller, Oral Absorption Enhancement by Nanocarrier Technology, European Workshop on Particulate Systems (EWPS), 2008.

M. Muchow, N. Ubrich, P. Maincent, and R. H. Müller, Nanostructured Carriers for Oral Testosterone Delivery, Pre-Satellite Meeting of the 3rd Pharmaceutical Sciences World Congress, 2007.

M. Muchow, N. Ubrich, P. Maincent, and R. H. Müller, Lipid Nanoparticles and Nanosuspensions for Oral Drug Delivery, 2006.

M. Muchow, N. Despatova, E. I. Schmitz, and R. H. Müller, Omega-3 Fatty Acid-loaded Lipid Nanoparticles as Oral Food Supplement, AAPS), 2005.