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Ministrante: Jordi ^Botet

Farmacovigiläncia & LegislaEäo para a lndtistria Farmac6utica Ministrante: Eloisa Jubram

Problemas Relacionados com Medicamentos Ministrante: CIadys Marques Santana

Etapas

de Desenvolvimento de Produtos Cosm6ticos Ministrante: Maria Aparecida Lima Moreira

ServiEos Farmac6uticos: DispensaEäo e Acompanhamento Farmacoterap6utico Ministrante: Cladys Marques Santana

AtenEäo Farmac6utica no Contexto dos ServiEos Farmac6uticos Dirigidos ao Paciente

(Enfase

na RDC 44log)

Ministrante: Denise Funchal

Cestäo de Risco e Seguranga do Paciente Ministrante: Bruna Malagoli Martino

Processo de Acreditagäo no Setor Satlde Ministrante: Bruna Malagoli Martino

lnscriEöes Exclusivamente pela lnternet

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revista FärmacosäMedicamentos

taz

um especial focado

no

lnternational Seminar of Nanotechnology 2011

,

^re-

alizado pela Faculdade

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Ciöncias Farmacöutica da Universidade de Säo Paulo ^(FCF/USP)

e

pelo Sindicato da

lndüstria

de

Produtos Farmacöuticos no Estado de Säo Paulo (SINDUSFAR- MA), com o apoio do lnstituto Racine.

Com

a

participagäo dos mais re-

nomados especialistas internacionais como ministrantes do ^evento,

o

lnter-

national Seminar of Nanotechnology 2011 pretende discutir as inovagöes

na ärea

de

nanotecnologia.

A t&lll,

publicagäo oficial do evento, por acre-

ditar

na

importäncia

de um

^evento como este para o aprimoramento e o desenvolvimento dos profissionais da ärea farmacöutica, apresenta o resumo

dos trabalhos premiados, com desta-

que para os trös trabalhos ^premiados, que abordam temas importantes para

a

ärea, como llposonres ^Radio/abe- led With 159CD-DTPA-BMA: Reieased

Profile and Encapsulation Efficiency of a Cancer Thera-

peutic Formulations, Nanostructured Passiflora Serrato- digitata L. Crude Extracts: A Nove/ Proposal for Antiulcer Therapy

e

Development and Characterization

of

Solid

Li p i d N an o p arti cl es Co ntai n i n g M etro n i d azo I e A n al o g u e for Treatment of Solid Tumors. Al6m destes, foram elen- cadas mais 21 menqöes honrosas äqueles que mais cor- responderam ä proposta do seminärio.

Aldm do Especial esta edigäo da F&M traz dois artigos de suas segöes fixas: Legislaqäo e Automagäo e lnformatizaqäo.

Na seqäo Legislaqäo o artigo aborda os estudos de prd-formulaqäo e sua importäncia para

o

desenvolvi- mento de produtos, que atualmente passa por aborda- gens cientificas e ^näo somente empiricas. Os estudos de prd-formulaqäo estäo inseridos na abrangöncia do _Quality by Design, ou Qualidade por Concepqäo, e esta etapa d importante no processo de desenvolvimento de produtos.

Os pesquisadores devem avaliar cuidadosamente esta etapa, considerando que antes de desenvolver o ^produ- to, a empresa deve saber e conhecer qual d a utilizaqäo pretendida do mesmo e qual _d o desempenho esperado.

A F&M aborda, na seqäo Automaqäo e lnformatizagäo, a importäncia da padronizagäo quando se trata da rastreabi- lidade de medicamentos. Padröes facilitam o dia-a-dia da indüstria e, mais importante ainda, contribuem para a se- guranqa do paciente. Processos e condiqöes näo automa- tizadas causam erros que, segundo o lnstitute of Medicine dos Estados Unidos da Amdrica (EUA), säo responsäveis pelo dbito de 7 mil individuos por ano do Pais.

Tambdm nesta ediqäo, o leitor poderä conferir os sites sobre nanotecnologia indicados por Maria Helena Andra- de Santana, docente da Faculdade de Engenharia Quimi- ca da Universidade Estadual de Campinas (UNICAMP) na segäo Navegue.

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"O professor pesquisador nas universidades ptiblicas assume, aldm do ensino de graduaqäo e de pös-graduagäo, as atividades de pesqulsa e de extensäo e ainda deve participar da gestäo de sua unidade. O ^professor deve otimizar seu tempo e saber reconhecer os parceiros valiosos que possam contribuir para os resultados esperados. Considero a revista Fätmacos&:Medicamentos de f undamental importäncia, afinal o professor universitärio d constantemente avaliado. A evoluqäo da tirea de Tecno- logia Farmac6utica, na tiltima ddcada, foi vertiginosa e acompanh;{-la em todas as suas nuances e facetas demonstrou ser taref a herctilea. A

leitura desse periödlco tem permitido minha rt{pida atualizaqäo, em especial nos assuntos tangenciais ä minha ;irea de interesse.

No que se refere ä pesquisa, essa atividade ccnstitui condigäo im- prescindivel para a formagäo de profissionais eficientes e capazes de criar inovagäo cientifica, cultural e tecnolögica, Etapa fundamental da pesqulsa refere-se ä divulgagäo de seus resultados para a comunidade cientftica e para a socledade. A revista Färmacost;Medicament0s, classificada pela Qualis, poder;i contribuir significativamente para a divulgaqäo das pesquisas no Pals. O termo _Qualis refere-se ao slstema de avaliagäo de periddicos mantido pela Coordenaqäo de Aperfeiqoamento de Pessoai

de N/ve/ Superior (CAPES). Ainda que classificada no nivel inicial, o

periödico poderä se /ortalecer em reduzido espaqo de tempo com a

uniäo de todos. Afinal, näo estamos, com freqüöncia, reclamando da

f alta de periödicos para as nossas publicaqöes?

Por fim, revelo motivo imponderävel para que a revista Färmac0s.*:Medicamentos

faga parte do meu dia-a-dia: sua estdtlca. Confesso minha atraqäo por

sua beleza, expressa nas capas, pelo miolo caprichoso que transborda a

dedicaqäo de quem a concebeu e pelo prof undo sentimento de respeito pela profissäo farmac€utica que emana de suas pdginas. Puro deleite."

1:

Marque um visto apds a leitura

Färmacosi;Medieamentos 65 laneiro Fevereiro. Marfo 201 1

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Marco de 2011

A revista FämacosäMedicamentos (ISSN 1Bo7-1678) d uma publicaqäo trimesiral da RCN Comercial e Editora Ltda., dirigida a empresas e profissionais das indr,istrias quimica, farmacöutica e farmoquimica.

i'i'ir :, i i.i i:: i .: i ! :

N ilce Barbosa t.l!;'::i:;; ;::, a::..iri i.:::, ir:

Arnivaldo Dias Marco Quintäo Renato Cintra Sdrgio Slan

Nilce Barbosa - CRF-SP 9.609

Andrd Policastro - MTb 12.771

::.r r':.:iir,:,r i{. ,r'.i:;::.,. : ^r Kelly Monteiro - Mfb 06.447 Sandra Aquino C. Moretto - cRQ-tv 01226912

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Adriano Brandelli, Alberto Vetore-Ncto, Alexandre Comes Rodrigues, Ana ^paul de Sousa Pereira, Ana Ramos, Andrc Rolim Baby, Andre Santos, Bruna Souza, Carclina Zanolini, Celso Valcntim Santilli, Christianc pienna Soares, Cibele Rosana Ribeiro de Castro Llma, Cristina Duarte Vianna Soares, Däniel Cristian Ferreira, Daniel G. Carboni, Delia Luna, Delia Pinb, Edith Kanashiro, Eduardo Burgarelli Lages, Elfriede Marianne Bacchi, Flizabeth lgne Ferreira, Elofsa Berbel Manaia, Elton Luiz Silva, Erika Rosa Maria Kedor, Cilson Anclrade Ramaldes, Cuilhcrme Canreiro, Cuilherme Diniz Tavares, Harry Wysocki, lolanda Cuc- covia, lsadora Marques Brum Conqalves, lair Calixto, Jeanine Ciarola, Johnny Lima, Joyce Santos Quenca-Cuillcn, Juliana Conte, Juliana Denise Conte, Kaila Cirlcne Alves Botelho, Kcrly F. M. Pasclualoto, Leandro Santoro Hernandes, Leila Aparecida Chiavacci, Leila Rodrigues Calcieira, Lidiane Advincula de Ararijo, Lis Marie Monteiro, Lucas ADtönio Miranda Ferrcira, Marc Slrasser, Marcos Moretto, Maria Betänia de Freitas, Maria Helena Andrade Santana, Maria lnös Rocha Miritello Santoro, Maria Segunda Aurora-prado, Maria Valeria Robles Velasco, Mariana Mandelii de Almeida. Marrlia Tamaki. Marina ^paiva Abuqaf, Mönica Cristina de Oliveira, Naciia Arabi Bou-Chacra, ^patrrcia da Silva Malheiros, Paulo Cdsar Cotrim, Peky Noriega. Rafaela C. Souza, Renata Barbos:

De Oliveira, Renata Cristina Kiatkoski Kaminski, Rerata de Oliveira Barbosa, Ricardo josd Alves, Sandra Helena Pulcinelli, Sonia Maria Malmonge, Soraya S.

Santos, Suelen Warigoda, Telma Mary Kaneko, Tulia de Souza Botelho, Valbert Nascimento Cardoso, Vanessa Pranco Tavares, Viviane Ferre, Vladi Olga Consiglieri e Wilson Cruz

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Artigos e matdrias assinaclas näo refletem necessariamente a

opiniäo da RCN Comercial e Editora Ltda.

Arquivo Racine e divulgaqäo.

Rua Padre Chico, 93

CEP 05008-01 0 - Säo Paulo - SP

Tel/Fax: ⁽¹ 1) 3670-3199 E-mail : [email protected]. br

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Seminärio Internacional

Debate InovaEöes em lr{anotecnologia

International Seminar of Nanotechnology 20ll

Faculdade de Ciöncias Farmacöuticas da llniversidade ^de Säo Paulo _(FCVUSP) 4 e 5 de abril de 20ll

Realizagäo

SINDUSFARMA

!rNDlcAro DA NoüstRrA JE PRoDUToS rARMACautrcos No FsrAirc DE sÄo ^pA!Lo

Apoio

Faculdade de Ciöncias Farmac6uticas da Univer- sidade de Säo Paulo (FCF/USP) e o Sindicato da lndüstria de Produtos Farmacöuticos no Estado

de Säo Paulo (SINDUSFARMA) realizam, nos dias

4 e

5 de abril de 2011,

o

lnternacional Seminar

of

Nanotechnology 2011, no Audi- tdrio da FCF/USB com

o

apoio

do

lnstituto Racine e da Revista Färmacosii:Medicamentos como publicaqäo oficial.

Este congresso tem como objetivo proporcio- nar uma compreensäo detalhada e discuiir as inovagöes da nanotecnologia que estäo sendo implementadas. Especialistas internacionais participam

do

evento, entre eles

o

^profes-

sor Rainer

H.

Müller, fundador da empresa

PharmaSol CmbH em Berlin, Alemanha, ^e inventor de 20 famflias de ^patentes e Salomon

A.

Stavchansky, Ph.D, que integra

o

comitö internacional da sar-lde aldm de ser membro do comit6 executivo do conselho de ^peritos da USP em biodisponibilidade e membro do comit6 de politica da USP.

A

Revista Färmacos,:j:Medicamentos faz parte deste projeto por compreender

a

^releväncia deste assunto para

a

indüstria farmacöutica

e

para

o

setor saüde em geral, com enorme potencial de oportunidades e desenvolvimento.

Neste contexto, apresenta nesta ediqäo especial os resumos dos trabalhos premiados. Confira nas päginas a seguir.

:r;i I FärmacosaMedicamentos 65 laneiro/Fevereiro/Marqo ^{201 1}

I Colocado

Liposomes Radiolabeled With 159GD-DTPA-BMA:

Released profile _and Encapsulation Efficiency of a cancer Therapeutic Formulations

Daniel Crfstian Ferreira, Mönica cristina ^de oliveira, valbert ^Nascimento Cardoso e Gilson Andrade ^Ramaldes

.aculty

of

Pharmacy, Federal L)niversity of Minas cerais, Belo Horizonte, ^Brazil

Purpose: This work aims at preparing

lH

sensitive liposomes encapsulating l59Cd radioisotope and studying ^the errcapsulation efficiency and ^released profile of this formulation in ^DEMEM culture cell medium and mouse serum.

Material and Methods: DOPE/CHEMSi DSPE-PEC liposomes encapsulating 159CD-DTPA-BMA were PrePared using the reverse-phase evaporation method. The vesicles were submitted :o a neulron irradiation on ^{a TRIGA}

\AARK-l IPR-R1 nuclear reactor ^{at the} CDTN-CNEN during B hours. ^The

;iposomes were physical-chemistry

characterized to verify structural ^in- tegrity. ^The concentration of released gadolinium ^present in the supernatant was analyzed by ICP-OES technique' Results and Conclusions: The ^re- sults show that vesicles ^maintained

perfectly the structural

^integrity.

The study of the kinetics

of

release of gadodiamide ^show that onlY 13.5 percents

of

radioactive gadolinium was released from liPosomes in the

f

irst

1,440 minutes and after 500 minutes of incubation we found out ^a tendency of thermodynamic stabiliza- tion ^{in the system} with 14.5 percent o{

gadolinium released. The encapsula- tion ef{iciency ^study was performed calculating the ratio of the number of mol of gadolinium encapsulated ⁱⁿ liposomes and the number of moles of total gadolinium ^used in preparation' The results obtained show encapsula- tion

of

19.1 '/" with 0'91 of ^standard deviation. ^Thus, we can conclude ^that the formulation resisted adequately the neutron irradiation ^{process and} showed an appropriate characteristic of encapsulation and released kinetics

in the studied condilions.

Financing: ^FAPEMIC; CNPq; CNEN

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2" Colocado

Nanostructured Passiflora serratodigitata L. Crude Extracts: A ^Novel Proposal for

Antiulcer Therapy

Marc Strasser (PG), Nadia Araci Bou-Chacra, Elfriede Marianne Bacchi Department of Pharmacy, Faculty of Pharmaceutical Sciences, U5P

lntrcducticn

and Objectives: The

goal

of this work

was

to

prepare and characterize nanoparticles ^(NP) containing crude extract ^(CE) and

ethyl

acetate

fraction

^(EAF)

of

^P.

serratodigitata and comparing the therapeutic

efficacy

between the products on an in vivo ulcer model.

Material and Methods: The

^NP were prepared by pre-formed poly- mer precipitation method, consist- ing of the addition under stirring of

the

organic phase containing poli (e-caprolactone) as the polymer on the aqueous phase. The solvent was

removed using reduced ^pressure

evaporator and

the final

volume was adjusted with water. The mean diameter and polydispersivity index (PDl) were measured using a Coulter Submicron Particle Size Analyzer.

The encapsulation

efficiency

^(EE) was evaluated using total flavonoid quantification by spectrophotometry in the ultrafiltered, after centrifugation

of

the colloidal suspension treated

with

acetonitrile. Pharmacological study was conducted in Wistar rats,

by the acute acidified ethanol ulcer induction model.

Rerults

and

Conclusions; The EE

for CE and EAF was 91o/" and BOo/"

respectively. The mean diameters anc the PDI were 379,2 *" 16,4 nm ^(0.253 and 383,8 + 18,2 nm (0.353), respec tively for CE-NP and EAF-NP. Botl NP showed unimodal distribution o

particles. The CE-NP system showec better antiulcer activity protection wher compared to the same dosage as CE

and same protection for EAF-NP anc EAF in dosage ten times lower ^{(50 >}

5 mg/kg: 907o protection). This dau shows

a

successful plant-derivatec nanoparticle formulation, with better

oral efficacy when compared

to

^;

non-nanostructured product.

Financial support: FAPESP

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rarmacosgtMedicamentos 65 3" Colocado

Development and Characterization of Solid Lipid Nanoparticles Containing Metronidazc Analogue for Treatment of Solid Tumors

Maria Betänia de Freitas (PG), Eduardo Burgarelli lages (lC), lsadora Marques Brum Gongalves (lC), Cristina Duarte Vianna Soares; Lucas

Antönio Miranda Ferreira e Renata Barbosa de Oliveira Departmenl of Pharmaceulics ProducIs, FafarlLJ FMC

lntroduction

and Obiectives: An- titumor activity

of

1-(2-iodoethyl)- 2-methyl-5-nitroimidazole (MTl), ^a metronidazole analogue, was recently evaluated, using mice bearing ^solid Ehrlich tumor, and patented by our research group. This

work

aimed to develop solid lipid nanoparticles (SLN) loaded with MTI for ^treatment of solid tumors.

Material and Methods: Preformulation studies were carried out. Development and validation of analytical method for the determination of MTI ^concentra- tion in SLN were also performed ^bY

spectrophotometry and HPLC. The SLN were prepared as following: ^oil lCompritol@ ^BB8 ATO, cholesterol, Tween@ 80, with or without ^stearyl- amine ^(STE) and MTI ⁽¹ mg/ml)l and aqueous (glycerin and water) phases

were heated

to

75"C and then the aqueous phase was slowly added to the oil ^phase and homogenized using

an Ultra-Turrax T25

for 2

minutes.

This formulation was immediately introduced

to

the probe sonication for 10 minutes, using a high intensity ultrasonic processor. The

pH

was adjusted ro 7.0-7.5 with 1 M HCl. A placebo formulation was also prepared

for comparison purpose. The SLN w characterized for size, encapsulati elliciency ^(EE) and zeta potential.

Results and Conclusions: ^The corporation of MTI not induced ^z significant change, neither with reg

to the mean particle size (< 250 r nor to polydispersion index value:

0,4) when MTI-loaded and blank ^S are compared. The EE for MTI in ^S with ancl without STE was ^{66o/o z}

217o respectively. The SLN remair stable alter 90 days of storage. I antitumor activity of the MTI-loac NLS

will

be evaluated.

faneiro/Fevereiro/Margo 20I 1

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Bulk Solution and Microfluidic Channels ^Processes

E*:

ttre

Sy*ä!^*esis

*f hlyaluronic Acid Nancparticles

Rafaela

c.

^{Souza (Pc)1, viviane Ferre (PG)1, lohnny Lima} (lc)1, Daniel G.

Carbonil(PG), Sonia Maria Malmonge2, Maria Helena Andrade Santanal- 1. school of Chemical Engineering, UN|CAMP;2. Biomedical Engineering, UFABC

li'rtrceiucti*n ^ae'rd Obiectives: ^Hyal- uronic acid nanoparticles (HAN) ^are

synthesized through discontinuous bulk processes, such as w/o emulsification and nanoprecipitation. ^{The f irst case} includes surfactants and

oil,

while nanoprecipitation is ^f ree

of

those components. Nanoprecipitation ^also could be performed

in

continuous mode, through microfluidic ^channels.

ln order to ^{gain insights on} the useful processes for the ^sYnthesis of HAN, we investigated the main variables of

each process and the physico-chemical properties of the nanoparticles. Herein we present a comParison among the studied ^{processes and} the ^produced nanoparticles.

Material and Methcds:

The dis- continuous process was carried out in a jacket ^glass reactor of 400 ^mL, equipped

with a

mechanical stirrer (model TE-039/1, Tecnal). The tem- perature in the reactor was controlled by circulating water from a thermostat

bath (model TE-184, Tecnal). HA with molecular weight 2,000 Da was used

in its salt form HNa from a ^{1% solu-} tion. Emulsification included a mineral

oil and the surfactants, a mixture of

Span B0 and Tween 80. NanoPreciPi-

tation used acetone

or ethanol.

ln

both cases, the nanoParticles ^were crosslinked

by

adipic dihydrazide

and

^{3 -d} imethylam inopropyl-3 ^{-eth -} ylcarbodiimide EDCI. The continu- ous ^process was carried

out

^inside

a crossflow microchannel ^{system, as} shown

in

Figure 1. Typically, ^aque- ous phase with HA, ADH and EDCI

was pumped into the main ^channel.

At the ^same time, the organic Phase

(with acetone

or

ethanol) was ^fed into both branch channels ^using two identical

but

separate syringes ^by another ^pump which could hold two

syringes and ensure an equal flow rate.

Both ^processes were studied in scal- able setups. Regarding emulsification process, we studied the influence of agitation, the kind and concentration

of surfactants, while in nanoprecipi- tation ^processes we investigated the effect of the ^solvents on the ^average diameter, polydispersity index ^and zeta potential of the nanoparticles.

Results and Conclusions: Emulsifica-

tion

^{process produced}

a

mixture of nano and microparticles, independent of the used surfactant ^{sYstem. The} separation

of

nanoparticles from ^oil was time consuming ^and and reduced the yield of process. Nanoprecipitation produced nanoparticles only, with low polidispersity index. The ^surface ten- sion controlled the mean diameter and polydispersity index in the discontinuous process/ while in continuous ^process these parameters were controlled by

the affinity between water and ^the organic phase. Nanoprecipitation processes were simple, reprociucible and produced HA nanoparticles ^iree of oil and surfactant.

Financing: ^{FAPESP; CaPes;} C\Pq

.:l:: .tX',:

l:i {} i farmacos.ili:Medicamentos os j laneiro/Fevereiro/Mar9o ²⁰¹¹

Molecular Modeling as a Tool to Study Target Dendrimer potentially Leishmanicide

Soraya _S. Santos (Pg), feanine Giarola (pg), Kerly F. M. pasqualoto (pg) e Elizabeth lgne Ferreira

Department

of

Pharmacy, FCf /USp.

lntroduction and Obfectives: Leish- maniasis is considered _a supernegleted tropical disease which affects areas of exlreme pover[y. The searching for new and more eifective drugs is still an urgent need. Dendrimers are nanoparticles used as drug delivery syslems. Dendrimers containing lour [o six branches oi myo- inositol (core and directing group), mannose (directing group),

milii

r-acid (spacer) and hydroxymethylnitrofurazone (NFOH, bioactive agent) were designed as potentially targeted leishmanicide.

Molecular modeling methods were applied to obtain inlormation regarding to the firsl. generarions of leishmänicidä targeted drug dendrimer disassemblv in the presence of unspecific esterases.

Material and Melhods: The 3D model of a four branches dendrimer contain- ing NFOH and myo-inositol was built up and the geometry optimization was carried

out

employing _MM+

force

lield

without _any constrains.

Partial atomic charges were calcu- Iated using the AM1 semiempirical method. Energy minimization and molecular dynamics (MD) _simula- Lions

(l00,000

st.eps; step size

I

^fs

at 300 k) were performed employ- ing the MOLSIM 3.2 program. The

lowest energy conformation was selected from

MD

simulations ancl

the

electrostatic potenl.ial chares were calculated using the ab initio method HF/6-31C*.

Results and ccnclusion: The elec-

trostatic potential _indicated

_the

carbonyl carbon next to the direct- ing group as more likely to sulier a

nucleophilic attack since it showed a

lower electronic density clistribution.

Also, this carbonyl carbon presents a smaller steric hindrance reiniorc-

ing the

hypothesis

that it

would be

the

most promising

portion

to

sulier

the esler breaking

point

by

an enzymatic

action.

Dendrimers containing four to six branches with D-mannose as well as containing five

to

six branches

wiih

myo-inositol are already

in

^process.

Financing: FAPESP; CNpq

tärmaG0sit{Medicament0s 6s ! laneirolFevereiro/Mar9o 2011 ; ^{? 1}

'.

₁₁

Development of Nanoemulsions Loaded with Amphotericin B and Stearylamine for Treatment of Leishmaniasis

Leila Rodrigues Caldeira (Pg), Renata de Oliveira Barbosa e Lucas Antönio Miranda Ferreira.

Deparlment

of

Pharmaceutics, Faculty of PharmacylUFMC

lntroduction and Objectives: Nanoemul- sions loaded with amphotericin B (AmB) is a way to overcome both the toxic side effects resulting with the conventional formulation, a micellar complex with desoxycholate, and the high cost and difficulties of production involving the liposomal AmB. The aim of this study was to develop nanoemulsions loaded with AmB and stearylamine ^(SA). SA is a lipophilic amine which was used for formation of ion pairing to improve the encapsulation efficiency ^(EE), the stability of the formulation and also the efficacy of the treatment.

Material and Methods: The systems

were prepared by hot homogeniza- tion method using an emulsification- ultrasound followed by drug incor- poration. Formulations with different amounts of AmB were characterized to droplet size.

lt

was conducted a

stability study comparing the NE with O.2'/"

ol

AmB with or without SA at

the first and the 30th day.

Results and Conclusions: The mean

droplet size in lhe lormulations wilh 0, 0.1, 0.2 and O.5"/, of AmB was re-

spectively: 171,8

*

O,5; 167

t

2; 163

t

2 and 186,6 + 0,8 nm. The stability study showed the significance of SA in

the maintenance of droplet size since

the formulation without SA presented increase in size (from 189

i

6 nm to 236

t

²³ nm) and the formulation with SA was capable of retaining

it

^tfrom

163 + 2 nm to 167

t

3 nm). And also, only the formulation without SA shorved increase in the polydispersitf index in thirty days, which was atror,e 0.3. ivhat makes

it

unacceptable

to

^parenteral

purpose. lt was not detected din-erences in EE between the formulations w'ith or without SA, both of them lrere capable of retaining high EE {90 = leo _{and 87,2} + O,2"/o to the formulation without or with SA respectivelvr.

Financing: Fapemig; C\Pq

:4 ? ! färmacos&Medicamentos os ! laneiro/Fevereiro/Mar9o 201 l

ot"."*,'

Tl*2 Nanoparticles with Centrolled Size Prepared Y Sol-Cel ^process for Use in

$*nscr*e* Formulaticns

Eloisa Berbel Manaial, Renata cristina Kiatkoski Kaminski2, celso Valentim santilli'?, sandra Helena Pulcinelli'?, Christiane pienna soares e Leila Aparecida Chiavaccil

1. Faculty of Pharmaceutical science/t)NESp; 2. lnstitute of Chemistry/uNEsp

lsrtrcductian and objective: ln Brazil, the skin cancer is the most frequent, corresponding approximately 25o/o of all diagnostics tumors in the country. The TiO2 is an inorganic compound used as

sunscreen in cosmetic/pharmaceutical formulations that is a way to prevent the skin cancer. By an appropriate synthesis

of TiO2 nanoparticles it is possible to obtain particles with desirable size, transparence and adequate protection of the skin from UVA and UVB radiations.

It is also possible to incorporate anti cancer drug for controlled release to the

Ti02 nanoparticles based formulations.

Materials and Methads: To control

de

size

of Ti02

nanoparticles for sunscreen applications it was used an unprecedented thermo-reversible sol- gel transition for titania nanoparticles dispersed in ^p-toluene of sulfonic acid (PfSH) isopropanol solution. Controlling the parameters of this reaction, it was possible to obtain different nanoscopic characteristics. Samples were studied kinetically by turbidimetry, with tem- perature ranging from 5 to 60"C. The

Ti02

nanoparticles were evaluated by an "in vitro" assay violet crystal to analyze rheir citotoxicity.

Results and Conclusion: The turbidimetry measurements indicate that between 30 and 600/o of the nanoparticles are transparent. ln the violet crystal assay the nanoparticles showed no citotoxic-

ity significantly on the two cell lines

tested, l<eratinocytes and fibroblasts humans, presenting above 70% of cell viability. The results evidence that it's possible to obtain TiO2 nanoparticles by the process sol-gel and applv them in sunscreen s formulalions on account of its transparency and no citotoricity.

Sinancing: FAPFSP

äa flmac0s&:Medicament0s 65 ! laneiro/Fevereiro/Margo 201 1

Fhysicochemical Characterization of ^Liposomes Containing the Antimicrobial Peptide Nisin

Patricia da Silva Malheiros (Pg) e Adriano Brandelli Department of f ood Science. ICTAIUFRCS

lntroduction and Objectives: Nisin is a

3.5 kDa cationic antimicrobial ^peptide recognized as safe for food applications.

Encapsulation of antimicrobial ^peptides into liposomes may offer a ^poLential alternative

to

protect antimicrobials, enhancing their eificacy and stability.

ln this work, nisin was encapsulated in liposomes of partially purified soybean phosphatidylcholine and their physico- chemical characteristics were evaluated.

Material and Methods: ^Commercial nisin was encapsulated in liposomes by hydration

film

method. Size and polydispersity (PDl) were evaluated by light scatterinB analysis. ^Residual antimicrobial aclivity of ^{free and en-}

capsulated nisin was tested by agar

diffusion assay. The Zeta potential analyses were carried

out

using a Tetasizer. Encapsulation eff iciency ^(EE) was assessed by ultra filtration using filters of 10 KDa. Morphological ex- amination of liposomes was performed using scanning electron microscope.

Results and Conclusions: The size of Iiposomes containing nisin ranged

from 142

to

132 nm and PDI from 0.355

to

0.290 during

24

^days to

4

^"C. Measured Zeta potential was -54.5 mV. Nisin had ^EE

of

94.12o/o.

Regarding

the

antimicrobial activ-

ity, it

was observed that free nisin remained 100%

of

residual activity

while encapsulated nisin was losing their antimicrobial activity over time reaching 25o/o afler 10 days.

lt

^was

observed by microscopy that the li- posomes maintained their spherical morphology.

Our

results indicate that nisin was easily incorporated, with high EE, in liposomes made of partially purified PC obtained from industrial soy byproduct. The stabil-

ity

observed by size and indicated by highly negative zeta potential was not the same regarding antimicrobial activity, indicating that the Iiposomes should be applied shortly after ^its preparation

Financing: ^CNPq

Fätmac0sgmedicamenl0s 65 i laneiro/Fevereiro/Margo 201t I ii

Development of Nanoemulsions and Solid Lipid Nanoparticles Loaded with Retinoic Acid and a Lipophilic Amine for Treatment of solid Tumors

Guilherme Carneiro ^(Pg), Elton [uis silva ^(Pg), Ana ^paula De Sousa pereira (lc), Mönica Cristina De Oliveira e Lucas Antönio Miranda Ferreira.

Department

o[

Pharmaceutics, taculty

of

pharmacy/UtMC

lntroduction and Objectives: All-trans retinoic acid (RA), a lipophilic vitamin

A

derivative, has been investigated

in

the trealment

of

cancer. Due to

the highly variable bioavailability of oral RA, development of allernative parenteral dosage forms is required.

Nanoemulsions (NE) and solid lipid nanoparticles (SLN) can favorably alter the chemical stability and biological activities of RA. However, encapsula-

tion efficiency ^(EE)

in

both systems

is usually low. The aim of this

study

Results and conclusions: The EE in

was to develop novel lipid

carriers,

NE with 0, 0..l and 0.2./. of SA was namely NE and SLN, loaded with RA

and stearylamine (SA),

a

lipophilic amine, which was used for formation of ion pairing with _{RA, a} lipid acid, and to improve the EE.

Material and Melhods: Both systems were prepared by hot homogenizalion method using an emulsification-ultra- sound. Lipid carriers were character- ized for EE, size and zeta potential.

62 + 4.5; 98

t

3.5 and 99

i

3.5ok respectively. ln SLN with

0

and 0.2"/o

of SA, the EE was 66 + 1 and .l01

+

7"/o, respeclively. Therefore, the ^EE in NE and SLN significantly improved in presence of the lipophilic amine.

Size ranged from 70

to

121 nm for NE and lrom 144 to ¹⁶⁷ nm for SLN.

ln

conclusion, the formation

of

ion pairing between RA and SA increasecl

the EE. These systems present poten- tial for controlled release of ^RA after parent.eral administration.

Financing: Fapemig; CNPq

?* ! farnacos,gmedicamentos os j laneiro/Fevereiro/Mar9o 2011

,,€

i*

ln vitro cytotoxic Activity of Liposomes Radiolabeied with on RtZ Tumoral Cells

Daniel Crfstian Ferreira Soares e Gilson Andrade Ramaldes

Faculty

of

^Pharmacy, Federal lJniversity

of

^Minas cerais, Belo Horizonte. Brazil

Purpose: To investigate the cytotoxic effecl of radiolabeled pH sensitive liposomes with 59Cd, a beta-emitting radionuclide,

on in vitro RT2 tumoral cells.

Material and _{Methods; Liposomes}

(DOPE, CHEMS, and DSpE-pEG) conrain- ing 159Cd-DTPA-BMA were prepared following the method of evaporation in reversed phases and labeled through a neutron activation process in a nuclear Reactor. lncreasing concentrations of the formulation were added

to

RT2 culture cells to determine the 1C50. A blank liposome formulation was used as a control group.

Results and Conclusions: Results from

the control group _indicated that a

lipid concentration of less than 3 mM would be sufficient enough to elimi- nate a significant percentage of RT2

cells. Therefore, the lipid concentra- tions used in the present study were below

3

mM. The non-radioactive Cd-DTPA-BMA complex presents _an lC50 of 20 + 1.4 mM, which in turn acts against RT2 tumoral cells after 4B hours of treatment. However, inside the liposomes from the present _stucly,

the lC50 value was found

to

be 66

+

8

/rM,

thus revealing

a

300-fold increase

in

its cytotoxic activity. ln contrast, when using the radiolabeled liposomes, the lC50 found was 1Z

I 5

^pM. This value is approximately

159gd-Dtpa-Bma

4 times

lower than

that found

in non-radiolabeled formulations and 1,162 times _lower than that found

in the

non-radioactive

free

metal complex. This increase in cytotoxic

activity

may

well

be explained by the ability

of

liposomes

to

increase the concentration in the intracellular environment through internalization.

Moreover, experimental procedures have shown that ionizing radiation is able to promote the activation of the p53 protein and leading to cell death by apoptosis. However, the elucidation

of the

real mechanism calls for further investigation.

Financing: FAPEMIC; CNpq; CNEN ll ä l falmacosi'iMedicamenl0s 65 ; laneiro/Fevereiro/Marco 2011

Preparation and Characterization of Polymeric Nanoparticles Containing Passiflora Extracts

peky Noriega (Pd), Marc strasser ^(Pg), Delia ^Luna(Pg), Andre santos(lc), Alberto Vetore-Netä(Lc), Leandro Santoro Hernandes ^(Pg), Elfriede Bacchi e Nadia ^Bou-Chacra

Department

of

PharmacY, FCIIUSP

lntroduction ^and Obiectives: ^{The oral} therapeutic efficacy

of

passifloras flavonoids can

be

imProved ^using nanostructured crude extracts ^(CE) of P.alata, P. edulis and ^P. serratodigitata' The goal of this work was to Prepare and characterize nanoparticles ^con- taining the flavonoids from the CE of these plants.

Material and Methods: The NC were prepared by pre-formed polymer ^pre- cipitation method, consisting

ol

^the

addition under slirring of the organic phase containing poli(epsilon -caprolac- tone), acetone, sorbitan monostearate, Miglyol @ 810 and CE on the aqueous phase containing polysorbate 80. ^The mean diameter and polydispersivity

index were measured using a Coulter Submicron Particle Size Analyzer.

The encapsulation

efficiency

^(EE)

of

Passiflora species was evaluated measuring the total flavonoids ^con- tent by spectrophotometric ^method based on the formation of comPlex with aluminum ion (Al+3) at 425nm in the ultrafiltered

of

colloidal sus-

pension, after cenlrifuBalion 10.000 rpm by

l0

min, using the ^quercetin

as marker. Detection was carried out in microplate Synergy-BioTek Reader.

Results and Conclusions: The results

were:

1) Mean Diameter (nm): ^P.

alata: 380.6, ^P. edulis: 350.9, P. ser-

ratodigitata: 300.5 and Blank: 240.2;

2) Polydispersivity lndex: P. alata:

0.318, P. edulis: 0.183, P. serrato- digitata: 0.253 and Blank: 0.154: ³⁾ Encapsulation Efticiency(7o): ^{P. alata:}

0.0, P. edulis: 60, ^P. serratodrgitata:

82 and Blank: 0.0; ^{and f} inallY 4) Zeta Potential (mV), P. alata:

-

31.8, ^P.

edulis: -33.1, P. serratodigitala ^-20.2 and Blank:

-

53.6. The encaPsulation of the extracts

of

Passiflora species by pre-formed polymer precipitation method showed adequate to _Prepare

the

nanoparticles

of

P. edulis ^and

P. serratodigitata extracts indicating their potential ^{use as a drug} delivery system; however

this

method not showed satisfactory results to P. alata.

Financing: CAPES/PRODOC; ^FAPESP;

CNPq

t

Ftrmac0si*Medicament0s 65 i Janeiro/Fevereiro/Ma r9o 2o1 r j ^? li