TY  - THES
AU  - Bubić Pajić, Nataša
PY  - 2020
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=7642
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:22707/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=18378761
UR  - https://nardus.mpn.gov.rs/handle/123456789/17504
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3719
AB  - Primarni cilj istraživanja ove doktorske disertacije je bila procena mogućnosti da se razvojemi primenom mikroemulzija (kao opcije hemijskog inhensera penetracije) poboljša dermalnaisporuka slabo rastvorljivih lekovitih supstanci – adapalena (ADA) i sertakonazol-nitrata (SN), kojepripadaju različitim farmakoterapijskim grupama, imaju različite fizičkohemijske osobine iprimenjuju se u različitim terapijskim koncentracijama. Mikroemulzije su stabilizovane nejonskimsurfaktantima novije generacije – alkil poligukozidima (APG) ili polioksietilen(glicerol) estrimamasnih kiselina. U cilju komparativne procene doprinosa različitih vrsta nosača dermalnojraspoloživosti model leka, posebna pažnja je posvećena analizi sposobnosti različitih vrstamikroigala (fizički inhenseri penetracije) da pojačaju isporuku SN u kožu (čvrste silikonske vs.rastvorljive mikroigle).Rezultati su ukazali da se još uvek nedovoljno korišćeni APG surfaktanti i gliceret-7-kaprilat/kaprat mogu uspešno primeniti u formulaciji mikroemulzija. Razvijene (invertne)bikontinuirane mikroemulzije su se pokazale kao pogodni nosači za solubilizovanje ADA i SN, upogledu njihovih fizičkohemijskih osobina, bezbednosti i stabilnosti, i, najvažnije, u pogledunjihovog potencijala za poboljšanje dermalne isporuke ovih lekova in vitro. Dodatno, rastvorljivemikroigle su uspešno formulisane kao nosači za dermalnu isporuku teško rastvorljivog SN iobezbedile komparabilno deponovanje leka u koži kao mikroemulzije, međutim uz prisustvo invitro transdermalne isporuke dela primenjene doze leka. Sinergističko delovanje mikroigala imikroemulzija bilo je superiorno u odnosu primenu samog fizičkog i samog hemijskogpremošćivača barijere stratum corneum-a, bez značajnog povećanja permeacije leka.
AB  - The aim of this doctoral dissertation was to evaluate the possibility of using microemulsions(as chemical penetration inerters) for improvment of dermal delivery of a poorly soluble modeldugs having different physicochemical characteristics, belonging to different pharmacotherapeuticgroups, i.e. applied in different therapeutic concentrations (adapalene (ADA) and sertaconazolenitrate (SN)). Microemulsions were stabilized with newer nonionic surfactants - alkylpolygucosides (APG) or polyoxyethylene (glycerol) fatty acid esters. In order to compare thecontribution of different types of carriers to the enhancement of dermal availability of the modeldrug, a special attention has been paid to the assessment of microneedles ability to significantlyimprove delivery of SN into the skin (dissolvable vs. solid silicone microneedles).The obtained results showed that newer and so far insufficiently used APG surfactants andglycereth-7-caprylate/caprate can be successfully applied in the formulation of microemulsions. Thedeveloped (invert) bicontinuous microemulsion formulations have proved to be suitable carriers forsolubilizing the investigated model drugs, in terms of their physicochemical properties, safetyprofile and stability, and, most importantly, their great potential of improving dermal delivery ofADA and SN in vitro. In addition, dissolvable microneedles were successfully fabricated as carriersfor dermal delivery o highly lipophilic SN and provided comparable drug deposition in the skin asmicroemulsions, but coupled with transdermal delivery of a portion of the administered drug dose.The synergistic action of microneedles and microemulsions was superior over the application eitherof physical or chemical enhancer alone, without reaching a significant increase in drug permeationas compared to the use of dissolvable microneedles.
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Hemijski i fizički pojačivači dermalne isporuke slabo rastvorljivih lekovitih supstanci: uporedna ispitivanja mikroemulzija, čvrstih i rastvorljivih mikroigala
UR  - https://hdl.handle.net/21.15107/rcub_nardus_17504
ER  - 

@phdthesis{
author = "Bubić Pajić, Nataša",
year = "2020",
abstract = "Primarni cilj istraživanja ove doktorske disertacije je bila procena mogućnosti da se razvojemi primenom mikroemulzija (kao opcije hemijskog inhensera penetracije) poboljša dermalnaisporuka slabo rastvorljivih lekovitih supstanci – adapalena (ADA) i sertakonazol-nitrata (SN), kojepripadaju različitim farmakoterapijskim grupama, imaju različite fizičkohemijske osobine iprimenjuju se u različitim terapijskim koncentracijama. Mikroemulzije su stabilizovane nejonskimsurfaktantima novije generacije – alkil poligukozidima (APG) ili polioksietilen(glicerol) estrimamasnih kiselina. U cilju komparativne procene doprinosa različitih vrsta nosača dermalnojraspoloživosti model leka, posebna pažnja je posvećena analizi sposobnosti različitih vrstamikroigala (fizički inhenseri penetracije) da pojačaju isporuku SN u kožu (čvrste silikonske vs.rastvorljive mikroigle).Rezultati su ukazali da se još uvek nedovoljno korišćeni APG surfaktanti i gliceret-7-kaprilat/kaprat mogu uspešno primeniti u formulaciji mikroemulzija. Razvijene (invertne)bikontinuirane mikroemulzije su se pokazale kao pogodni nosači za solubilizovanje ADA i SN, upogledu njihovih fizičkohemijskih osobina, bezbednosti i stabilnosti, i, najvažnije, u pogledunjihovog potencijala za poboljšanje dermalne isporuke ovih lekova in vitro. Dodatno, rastvorljivemikroigle su uspešno formulisane kao nosači za dermalnu isporuku teško rastvorljivog SN iobezbedile komparabilno deponovanje leka u koži kao mikroemulzije, međutim uz prisustvo invitro transdermalne isporuke dela primenjene doze leka. Sinergističko delovanje mikroigala imikroemulzija bilo je superiorno u odnosu primenu samog fizičkog i samog hemijskogpremošćivača barijere stratum corneum-a, bez značajnog povećanja permeacije leka., The aim of this doctoral dissertation was to evaluate the possibility of using microemulsions(as chemical penetration inerters) for improvment of dermal delivery of a poorly soluble modeldugs having different physicochemical characteristics, belonging to different pharmacotherapeuticgroups, i.e. applied in different therapeutic concentrations (adapalene (ADA) and sertaconazolenitrate (SN)). Microemulsions were stabilized with newer nonionic surfactants - alkylpolygucosides (APG) or polyoxyethylene (glycerol) fatty acid esters. In order to compare thecontribution of different types of carriers to the enhancement of dermal availability of the modeldrug, a special attention has been paid to the assessment of microneedles ability to significantlyimprove delivery of SN into the skin (dissolvable vs. solid silicone microneedles).The obtained results showed that newer and so far insufficiently used APG surfactants andglycereth-7-caprylate/caprate can be successfully applied in the formulation of microemulsions. Thedeveloped (invert) bicontinuous microemulsion formulations have proved to be suitable carriers forsolubilizing the investigated model drugs, in terms of their physicochemical properties, safetyprofile and stability, and, most importantly, their great potential of improving dermal delivery ofADA and SN in vitro. In addition, dissolvable microneedles were successfully fabricated as carriersfor dermal delivery o highly lipophilic SN and provided comparable drug deposition in the skin asmicroemulsions, but coupled with transdermal delivery of a portion of the administered drug dose.The synergistic action of microneedles and microemulsions was superior over the application eitherof physical or chemical enhancer alone, without reaching a significant increase in drug permeationas compared to the use of dissolvable microneedles.",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Hemijski i fizički pojačivači dermalne isporuke slabo rastvorljivih lekovitih supstanci: uporedna ispitivanja mikroemulzija, čvrstih i rastvorljivih mikroigala",
url = "https://hdl.handle.net/21.15107/rcub_nardus_17504"
}

Bubić Pajić, N.. (2020). Hemijski i fizički pojačivači dermalne isporuke slabo rastvorljivih lekovitih supstanci: uporedna ispitivanja mikroemulzija, čvrstih i rastvorljivih mikroigala. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_17504

Bubić Pajić N. Hemijski i fizički pojačivači dermalne isporuke slabo rastvorljivih lekovitih supstanci: uporedna ispitivanja mikroemulzija, čvrstih i rastvorljivih mikroigala. in Универзитет у Београду. 2020;.
https://hdl.handle.net/21.15107/rcub_nardus_17504 .

Bubić Pajić, Nataša, "Hemijski i fizički pojačivači dermalne isporuke slabo rastvorljivih lekovitih supstanci: uporedna ispitivanja mikroemulzija, čvrstih i rastvorljivih mikroigala" in Универзитет у Београду (2020),
https://hdl.handle.net/21.15107/rcub_nardus_17504 .

TY  - CONF
AU  - Bubić Pajić, Nataša
AU  - Ilić, Tanja
AU  - Nikolić, Ines
AU  - Vučen, Sonja
AU  - Dobričić, Vladimir
AU  - Savić, Snežana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5455
AB  - Efikasnost terapije gljivičnih infekcija kože zavisi od sposobnosti lijeka da premosti barijeru stratum
corneuma i dospije u vijabilni epidermis. S obzirom da su mnogi antifungalni lijekovi slabo rastvorljivi
u vodi i imaju nisku permeabilnost, razvoj pogodnih formulacija za efikasnu isporuku lijeka u kožu
nije jednostavan.
Cilj ovog rada je procjena efekta kombinovane primjene prethodno razvijenih biokompatibilnih
mikroemulzija i čvrstih silikonskih mikroigala na poboljšanu dermalnu isporuku antifungalnog lijeka
- sertakonazol-nitrata (SN).
Mikroemulzije su izrađivane dodatkom ulja (propilenglikol-monokaprilat) u smješu surfaktanta
i kosurfaktanta (gliceret-7-kaprilat/kaprat:etanol ili polisorbat 80: dietilenglikol monoetiletar)
uz miješanje u trajanju od 15 min. Nakon toga, odgovarajuća količina vode je postepeno dodana
i miješanje je vršeno dodatnih 15 min, nakon čega je u izrađenim uzorcima rastvoren SN (2%). In
vitro studije penetracije/permeacije sa ili bez predthodnog tretmana kože uha svinje ImmuPatch
silikonskim mikroiglama (Nacionalni Institut Tyndall, Kork, Irska) su sprovedene na Franz-ovim
difuzionim ćelijama.
Dobijeni rezultati su pokazali da je predtrtman kože mikroiglama značajno poboljšao isporuku SN
u koži iz obje ispitivane mikroemulzione formulacije. 24h nakon primjene uzoraka, količina lijeka
koja je deponovana u koži tretiranoj mikroiglama je bila veća 1,90-2,02 puta u odnosu na intaktnu
kožu. Međutim, količina lijeka koja je permeirala nakon 24h iz mikroemulzija kroz kožu tretiranu
mikroiglama je bila 26,96±7,88 μg/ml i 12,66±2,07 μg/ml, dok SN nije detektovan u akceptorskoj fazi
nakon primjene samih mikroemulzija.
Dobijeni rezultati ukazuju da bi kombinovana primjena mikroigala i biokompatibilnih mikroemulzija
mogla biti efikasan i bezbolan pristup za poboljšanu isporuku sertakonazol-nitrata u kožu. Međutim,
bez obzira na zanemarljivu permeaciju, odgovarajućim in vivo ispitivanjima na je potrebno potvrditi
odsustvo sistemskih neželjenih efekata.
AB  - The effectiveness of a topically applied antifungal agent is directly related to its ability to pass the barrier of the stratum corneum and to reach at least the viable epidermis. Given that many antifungals are poorly soluble and have low skin permeability, development of a suitable formulation is not an easy task. The aim of our study was to evaluate the effect of the combination of previously designed seraconazole nitrate (SN) loaded biocompatible microemulsions with solid silicon microneedles for enhanced dermal drug delivery. For the preparation of MEs, oil (propylene glycol monocaprylate) was added to the mixture of surfactant and cosurfactant (glycereth-7-caprylate/caprate:ethanol or polysorbate 80: diethylene glycolmonoethyl ether) and mixed for 15 min. Then, proper amount of water was added and mixed for another 15 min. SN (2% w/w) was dissolved in previously prepared MEs. In vitro skin penetration/ permeation studies with and without skin pretreatment with ImmuPatch silicon microneedles (Tyndall National Institute, Cork, Ireland) were conducted on Franz-type diffusion cells using porcine ear skin. Our finding revealed that skin pretreatment with microneedles significantly improved SN delivery into the skin from both tested microemulsions, resulting in 1.90-2.02-fold enhanced level of the drug retained in the skin, as measured 24h after administration. However, the drug permeated 24h after application of tested formulations combined with microneedles was 26.96±7.88 μg/ml and 12.66±2.07 μg/ml, whereas SN did not permeated through the intact skin. The obtained results suggest that combination of solid microneedles and biocompatible microemulsions could be an effective and painless approach for enhancing drug delivery into the skin. However, despite negligible SN permeation, further in vivo study should be performed in order to confirm the absence of systemic adverse effects.
PB  - Prisma - korporativne komunikacije
PB  - Farmaceutska komora Crne Gore
C3  - Treći kongres farmaceuta Crne Gore sa međunarodnim učešćem, 09 - 12. maj 2019. Budva, Bečići, Book of Abstracts
T1  - Kombinovana primjena silikonskih mikroigala i biokompatibilnih mikroemulzija za poboljšanu dermalnu isporuku sertakonazol-nitrata
T1  - Combined application of silicon microneedles and biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate
SP  - 118
EP  - 119
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5455
ER  - 

@conference{
author = "Bubić Pajić, Nataša and Ilić, Tanja and Nikolić, Ines and Vučen, Sonja and Dobričić, Vladimir and Savić, Snežana",
year = "2019",
abstract = "Efikasnost terapije gljivičnih infekcija kože zavisi od sposobnosti lijeka da premosti barijeru stratum
corneuma i dospije u vijabilni epidermis. S obzirom da su mnogi antifungalni lijekovi slabo rastvorljivi
u vodi i imaju nisku permeabilnost, razvoj pogodnih formulacija za efikasnu isporuku lijeka u kožu
nije jednostavan.
Cilj ovog rada je procjena efekta kombinovane primjene prethodno razvijenih biokompatibilnih
mikroemulzija i čvrstih silikonskih mikroigala na poboljšanu dermalnu isporuku antifungalnog lijeka
- sertakonazol-nitrata (SN).
Mikroemulzije su izrađivane dodatkom ulja (propilenglikol-monokaprilat) u smješu surfaktanta
i kosurfaktanta (gliceret-7-kaprilat/kaprat:etanol ili polisorbat 80: dietilenglikol monoetiletar)
uz miješanje u trajanju od 15 min. Nakon toga, odgovarajuća količina vode je postepeno dodana
i miješanje je vršeno dodatnih 15 min, nakon čega je u izrađenim uzorcima rastvoren SN (2%). In
vitro studije penetracije/permeacije sa ili bez predthodnog tretmana kože uha svinje ImmuPatch
silikonskim mikroiglama (Nacionalni Institut Tyndall, Kork, Irska) su sprovedene na Franz-ovim
difuzionim ćelijama.
Dobijeni rezultati su pokazali da je predtrtman kože mikroiglama značajno poboljšao isporuku SN
u koži iz obje ispitivane mikroemulzione formulacije. 24h nakon primjene uzoraka, količina lijeka
koja je deponovana u koži tretiranoj mikroiglama je bila veća 1,90-2,02 puta u odnosu na intaktnu
kožu. Međutim, količina lijeka koja je permeirala nakon 24h iz mikroemulzija kroz kožu tretiranu
mikroiglama je bila 26,96±7,88 μg/ml i 12,66±2,07 μg/ml, dok SN nije detektovan u akceptorskoj fazi
nakon primjene samih mikroemulzija.
Dobijeni rezultati ukazuju da bi kombinovana primjena mikroigala i biokompatibilnih mikroemulzija
mogla biti efikasan i bezbolan pristup za poboljšanu isporuku sertakonazol-nitrata u kožu. Međutim,
bez obzira na zanemarljivu permeaciju, odgovarajućim in vivo ispitivanjima na je potrebno potvrditi
odsustvo sistemskih neželjenih efekata., The effectiveness of a topically applied antifungal agent is directly related to its ability to pass the barrier of the stratum corneum and to reach at least the viable epidermis. Given that many antifungals are poorly soluble and have low skin permeability, development of a suitable formulation is not an easy task. The aim of our study was to evaluate the effect of the combination of previously designed seraconazole nitrate (SN) loaded biocompatible microemulsions with solid silicon microneedles for enhanced dermal drug delivery. For the preparation of MEs, oil (propylene glycol monocaprylate) was added to the mixture of surfactant and cosurfactant (glycereth-7-caprylate/caprate:ethanol or polysorbate 80: diethylene glycolmonoethyl ether) and mixed for 15 min. Then, proper amount of water was added and mixed for another 15 min. SN (2% w/w) was dissolved in previously prepared MEs. In vitro skin penetration/ permeation studies with and without skin pretreatment with ImmuPatch silicon microneedles (Tyndall National Institute, Cork, Ireland) were conducted on Franz-type diffusion cells using porcine ear skin. Our finding revealed that skin pretreatment with microneedles significantly improved SN delivery into the skin from both tested microemulsions, resulting in 1.90-2.02-fold enhanced level of the drug retained in the skin, as measured 24h after administration. However, the drug permeated 24h after application of tested formulations combined with microneedles was 26.96±7.88 μg/ml and 12.66±2.07 μg/ml, whereas SN did not permeated through the intact skin. The obtained results suggest that combination of solid microneedles and biocompatible microemulsions could be an effective and painless approach for enhancing drug delivery into the skin. However, despite negligible SN permeation, further in vivo study should be performed in order to confirm the absence of systemic adverse effects.",
publisher = "Prisma - korporativne komunikacije, Farmaceutska komora Crne Gore",
journal = "Treći kongres farmaceuta Crne Gore sa međunarodnim učešćem, 09 - 12. maj 2019. Budva, Bečići, Book of Abstracts",
title = "Kombinovana primjena silikonskih mikroigala i biokompatibilnih mikroemulzija za poboljšanu dermalnu isporuku sertakonazol-nitrata, Combined application of silicon microneedles and biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate",
pages = "118-119",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5455"
}

Bubić Pajić, N., Ilić, T., Nikolić, I., Vučen, S., Dobričić, V.,& Savić, S.. (2019). Kombinovana primjena silikonskih mikroigala i biokompatibilnih mikroemulzija za poboljšanu dermalnu isporuku sertakonazol-nitrata. in Treći kongres farmaceuta Crne Gore sa međunarodnim učešćem, 09 - 12. maj 2019. Budva, Bečići, Book of Abstracts
Prisma - korporativne komunikacije., 118-119.
https://hdl.handle.net/21.15107/rcub_farfar_5455

Bubić Pajić N, Ilić T, Nikolić I, Vučen S, Dobričić V, Savić S. Kombinovana primjena silikonskih mikroigala i biokompatibilnih mikroemulzija za poboljšanu dermalnu isporuku sertakonazol-nitrata. in Treći kongres farmaceuta Crne Gore sa međunarodnim učešćem, 09 - 12. maj 2019. Budva, Bečići, Book of Abstracts. 2019;:118-119.
https://hdl.handle.net/21.15107/rcub_farfar_5455 .

Bubić Pajić, Nataša, Ilić, Tanja, Nikolić, Ines, Vučen, Sonja, Dobričić, Vladimir, Savić, Snežana, "Kombinovana primjena silikonskih mikroigala i biokompatibilnih mikroemulzija za poboljšanu dermalnu isporuku sertakonazol-nitrata" in Treći kongres farmaceuta Crne Gore sa međunarodnim učešćem, 09 - 12. maj 2019. Budva, Bečići, Book of Abstracts (2019):118-119,
https://hdl.handle.net/21.15107/rcub_farfar_5455 .

TY  - JOUR
AU  - Bubić Pajić, Nataša
AU  - Ilić, Tanja
AU  - Nikolić, Ines
AU  - Dobričić, Vladimir
AU  - Pantelić, Ivana
AU  - Savić, Snežana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3453
AB  - Aiming to develop biocompatible microemulsions based on natural alkyl polyglucoside surfactant as prospective carriers for improved dermal delivery of adapalene, phase behavior and microstructure of pseudo-ternary oil/decyl glucoside/propylene glycol/water systems were evaluated. The chosen inverted bicontinuous formulations did not change their microstructure upon drug incorporation and remained stable during 1-year period. Preliminary in vivo assessment of skin performances suggested satisfying safety profiles of placebo microemulsions, in spite of considerable changes in skin hydration and barrier function. Interestingly, despite lower in vitro drug release, the amount of adapalene penetrated into porcine skin under infinite dosing regime was higher from microemulsions than from commercial drug product, reaching dermal retention enhancement ratio of 5.9. However, by changing experimental conditions to the more realistic in-use situation, the amount of adapalene extracted from the stratum corneum was comparable for microemulsions and marketed product. Similarly, the drug deposition in hair follicles was slightly pronounced with novel microemulsion vehicles (183.30 ± 156.32 ng/cm2 and 167.39 ± 108.96 ng/cm2 vs. 157.00 ± 114.91 ng/cm2), highlighting the importance of proper selection of experimental conditions when assessing trans(dermal) drug delivery. Consequently, our results suggest that alkyl polyglucoside based microemulsions are promising vehicles worth exploring further for targeted intraderdermal delivery of adapalene in acne treatment.
T2  - Journal of Drug Delivery Science and Technology
T1  - Alkyl polyglucoside-based adapalene-loaded microemulsions for targeted dermal delivery: Structure, stability and comparative biopharmaceutical characterization with a conventional dosage form
VL  - 54
SP  - 1
EP  - 12
DO  - 10.1016/j.jddst.2019.101245
ER  - 

@article{
author = "Bubić Pajić, Nataša and Ilić, Tanja and Nikolić, Ines and Dobričić, Vladimir and Pantelić, Ivana and Savić, Snežana",
year = "2019",
abstract = "Aiming to develop biocompatible microemulsions based on natural alkyl polyglucoside surfactant as prospective carriers for improved dermal delivery of adapalene, phase behavior and microstructure of pseudo-ternary oil/decyl glucoside/propylene glycol/water systems were evaluated. The chosen inverted bicontinuous formulations did not change their microstructure upon drug incorporation and remained stable during 1-year period. Preliminary in vivo assessment of skin performances suggested satisfying safety profiles of placebo microemulsions, in spite of considerable changes in skin hydration and barrier function. Interestingly, despite lower in vitro drug release, the amount of adapalene penetrated into porcine skin under infinite dosing regime was higher from microemulsions than from commercial drug product, reaching dermal retention enhancement ratio of 5.9. However, by changing experimental conditions to the more realistic in-use situation, the amount of adapalene extracted from the stratum corneum was comparable for microemulsions and marketed product. Similarly, the drug deposition in hair follicles was slightly pronounced with novel microemulsion vehicles (183.30 ± 156.32 ng/cm2 and 167.39 ± 108.96 ng/cm2 vs. 157.00 ± 114.91 ng/cm2), highlighting the importance of proper selection of experimental conditions when assessing trans(dermal) drug delivery. Consequently, our results suggest that alkyl polyglucoside based microemulsions are promising vehicles worth exploring further for targeted intraderdermal delivery of adapalene in acne treatment.",
journal = "Journal of Drug Delivery Science and Technology",
title = "Alkyl polyglucoside-based adapalene-loaded microemulsions for targeted dermal delivery: Structure, stability and comparative biopharmaceutical characterization with a conventional dosage form",
volume = "54",
pages = "1-12",
doi = "10.1016/j.jddst.2019.101245"
}

Bubić Pajić, N., Ilić, T., Nikolić, I., Dobričić, V., Pantelić, I.,& Savić, S.. (2019). Alkyl polyglucoside-based adapalene-loaded microemulsions for targeted dermal delivery: Structure, stability and comparative biopharmaceutical characterization with a conventional dosage form. in Journal of Drug Delivery Science and Technology, 54, 1-12.
https://doi.org/10.1016/j.jddst.2019.101245

Bubić Pajić N, Ilić T, Nikolić I, Dobričić V, Pantelić I, Savić S. Alkyl polyglucoside-based adapalene-loaded microemulsions for targeted dermal delivery: Structure, stability and comparative biopharmaceutical characterization with a conventional dosage form. in Journal of Drug Delivery Science and Technology. 2019;54:1-12.
doi:10.1016/j.jddst.2019.101245 .

Bubić Pajić, Nataša, Ilić, Tanja, Nikolić, Ines, Dobričić, Vladimir, Pantelić, Ivana, Savić, Snežana, "Alkyl polyglucoside-based adapalene-loaded microemulsions for targeted dermal delivery: Structure, stability and comparative biopharmaceutical characterization with a conventional dosage form" in Journal of Drug Delivery Science and Technology, 54 (2019):1-12,
https://doi.org/10.1016/j.jddst.2019.101245 . .

TY  - CONF
AU  - Bubić Pajić, Nataša
AU  - Nikolić, Ines
AU  - Dobričić, Vladimir
AU  - Savić, Snežana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5456
AB  - Adapalene (ADA) belongs to the group of retinoids,
synthetic analogs of retinol, and it is used as a first line
therapy of mild to moderate acne, with a few exceptions
(1). However, dermal availability of ADA is limited due to
its poor aqueous solubility. In order to enhance the drug
penetration into target areas (i.e. hair follicles and
epidermis), several strategies, such as liposomes,
microemulsions (MEs), solid lipid microparticles,
nanostructured lipid carriers etc., were proposed recently.
MEs have been reported as a promising tool for topical drug
delivery because they combine several advantages over
conventional formulations, including ease of manufacture,
high solubilization potential for poorly soluble drugs,
reduced side effects, long-term stability and improved drug
penetration through/into the skin (2).
C3  - 3rd European Conference on Pharmaceutics, 25 to 26 March, 2019, Bologna, Italy, Abstract book
T1  - Biopharmaceutical properties of adapalene loaded biocompatible microemulsions
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5456
ER  - 

@conference{
author = "Bubić Pajić, Nataša and Nikolić, Ines and Dobričić, Vladimir and Savić, Snežana",
year = "2019",
abstract = "Adapalene (ADA) belongs to the group of retinoids,
synthetic analogs of retinol, and it is used as a first line
therapy of mild to moderate acne, with a few exceptions
(1). However, dermal availability of ADA is limited due to
its poor aqueous solubility. In order to enhance the drug
penetration into target areas (i.e. hair follicles and
epidermis), several strategies, such as liposomes,
microemulsions (MEs), solid lipid microparticles,
nanostructured lipid carriers etc., were proposed recently.
MEs have been reported as a promising tool for topical drug
delivery because they combine several advantages over
conventional formulations, including ease of manufacture,
high solubilization potential for poorly soluble drugs,
reduced side effects, long-term stability and improved drug
penetration through/into the skin (2).",
journal = "3rd European Conference on Pharmaceutics, 25 to 26 March, 2019, Bologna, Italy, Abstract book",
title = "Biopharmaceutical properties of adapalene loaded biocompatible microemulsions",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5456"
}

Bubić Pajić, N., Nikolić, I., Dobričić, V.,& Savić, S.. (2019). Biopharmaceutical properties of adapalene loaded biocompatible microemulsions. in 3rd European Conference on Pharmaceutics, 25 to 26 March, 2019, Bologna, Italy, Abstract book.
https://hdl.handle.net/21.15107/rcub_farfar_5456

Bubić Pajić N, Nikolić I, Dobričić V, Savić S. Biopharmaceutical properties of adapalene loaded biocompatible microemulsions. in 3rd European Conference on Pharmaceutics, 25 to 26 March, 2019, Bologna, Italy, Abstract book. 2019;.
https://hdl.handle.net/21.15107/rcub_farfar_5456 .

Bubić Pajić, Nataša, Nikolić, Ines, Dobričić, Vladimir, Savić, Snežana, "Biopharmaceutical properties of adapalene loaded biocompatible microemulsions" in 3rd European Conference on Pharmaceutics, 25 to 26 March, 2019, Bologna, Italy, Abstract book (2019),
https://hdl.handle.net/21.15107/rcub_farfar_5456 .

TY  - JOUR
AU  - Bubić-Pajić, Nataša
AU  - Nikolić, Ines
AU  - Mitsou, Evgenia
AU  - Papadimitriou, Vassiliki
AU  - Xenakis, Aristotelis
AU  - Ranđelović, Danijela
AU  - Dobričić, Vladimir
AU  - Smitran, Aleksandra
AU  - Cekić, Nebojša
AU  - Čalija, Bojan
AU  - Savić, Snežana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3062
AB  - The aim of this study was development of biocompatible topical microemulsions (MEs) for incorporation and improved dermal delivery of sertaconazole nitrate (SN). For this purpose, phase behavior and microstructure of pseudo-ternary glycereth-7-caprylate/caprate (Emanon EV-E, EV)/cosurfactant/Capryol (TM) 90/water systems were investigated. Furhermore, the influence of these properties on the drug skin delivery was also assessed. Expansion of ME single-phase regions with the use of short chain alcohols was a consequence of the more fluid interface when compared to other investigated systems, which was confirmed by electron paramagnetic resonance spectroscopy-EPR. The chosen bicontinuous to inverted bicontinuous formulations were assessed against the ME based on polysorbate 80 as referent sample. Despite incorporation of SN within the selected formulations induced similar alternations in electrical conductivity, viscosity and pH values, obtained EPR spectra suggested different SN localization: within the oil phase (for most of the EV based formulations), or interacting with the interface (polysorbate 80 based formulation). Due to higher in vitro drug release (12.24%-18.53%), ex vivo SN penetration into porcine ear skin (dermal retention Enhancement Ratio (ERO) ranged from 2.66 to 4.25) and pronounced antifungal activity, the chosen MEs represent promising vehicles for dermal delivery of SN in treatment of cutaneous fungal infections. The biopharmaceutical and skin performance differences obtained with different formulations were possible to be explained on the basis of their physicochemical characteristics.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Molecular Liquids
T1  - Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties
VL  - 272
SP  - 746
EP  - 758
DO  - 10.1016/j.molliq.2018.10.002
ER  - 

@article{
author = "Bubić-Pajić, Nataša and Nikolić, Ines and Mitsou, Evgenia and Papadimitriou, Vassiliki and Xenakis, Aristotelis and Ranđelović, Danijela and Dobričić, Vladimir and Smitran, Aleksandra and Cekić, Nebojša and Čalija, Bojan and Savić, Snežana",
year = "2018",
abstract = "The aim of this study was development of biocompatible topical microemulsions (MEs) for incorporation and improved dermal delivery of sertaconazole nitrate (SN). For this purpose, phase behavior and microstructure of pseudo-ternary glycereth-7-caprylate/caprate (Emanon EV-E, EV)/cosurfactant/Capryol (TM) 90/water systems were investigated. Furhermore, the influence of these properties on the drug skin delivery was also assessed. Expansion of ME single-phase regions with the use of short chain alcohols was a consequence of the more fluid interface when compared to other investigated systems, which was confirmed by electron paramagnetic resonance spectroscopy-EPR. The chosen bicontinuous to inverted bicontinuous formulations were assessed against the ME based on polysorbate 80 as referent sample. Despite incorporation of SN within the selected formulations induced similar alternations in electrical conductivity, viscosity and pH values, obtained EPR spectra suggested different SN localization: within the oil phase (for most of the EV based formulations), or interacting with the interface (polysorbate 80 based formulation). Due to higher in vitro drug release (12.24%-18.53%), ex vivo SN penetration into porcine ear skin (dermal retention Enhancement Ratio (ERO) ranged from 2.66 to 4.25) and pronounced antifungal activity, the chosen MEs represent promising vehicles for dermal delivery of SN in treatment of cutaneous fungal infections. The biopharmaceutical and skin performance differences obtained with different formulations were possible to be explained on the basis of their physicochemical characteristics.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Molecular Liquids",
title = "Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties",
volume = "272",
pages = "746-758",
doi = "10.1016/j.molliq.2018.10.002"
}

Bubić-Pajić, N., Nikolić, I., Mitsou, E., Papadimitriou, V., Xenakis, A., Ranđelović, D., Dobričić, V., Smitran, A., Cekić, N., Čalija, B.,& Savić, S.. (2018). Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties. in Journal of Molecular Liquids
Elsevier Science BV, Amsterdam., 272, 746-758.
https://doi.org/10.1016/j.molliq.2018.10.002

Bubić-Pajić N, Nikolić I, Mitsou E, Papadimitriou V, Xenakis A, Ranđelović D, Dobričić V, Smitran A, Cekić N, Čalija B, Savić S. Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties. in Journal of Molecular Liquids. 2018;272:746-758.
doi:10.1016/j.molliq.2018.10.002 .

Bubić-Pajić, Nataša, Nikolić, Ines, Mitsou, Evgenia, Papadimitriou, Vassiliki, Xenakis, Aristotelis, Ranđelović, Danijela, Dobričić, Vladimir, Smitran, Aleksandra, Cekić, Nebojša, Čalija, Bojan, Savić, Snežana, "Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties" in Journal of Molecular Liquids, 272 (2018):746-758,
https://doi.org/10.1016/j.molliq.2018.10.002 . .

TY  - JOUR
AU  - Bubić-Pajić, Nataša
AU  - Todosijević, Marija N.
AU  - Vuleta, Gordana
AU  - Cekić, Nebojša
AU  - Dobričić, Vladimir
AU  - Vučen, Sonja
AU  - Čalija, Bojan
AU  - Lukić, Milica
AU  - Ilić, Tanja
AU  - Savić, Snežana
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2837
AB  - Two types of biocompatible surfactants were evaluated for their capability to formulate skin-friendly/non-irritant microemulsions as vehicles for two poorly water-soluble model drugs differing in properties and concentrations: alkyl polyglucosides (decyl glucoside and caprylyl/capryl glucoside) and ethoxylated surfactants (glycereth-7-caprylate/caprate and polysorbate 80). Phase behavior, structural inversion and microemulsion solubilization potential for sertaconazole nitrate and adapalene were found to be highly dependent on the surfactants structure and HLB value. Performed characterization (polarized light microscopy, pH, electrical conductivity, rheological, FTIR and DSC measurements) indicated a formulation containing glycereth-7-caprylate/caprate as suitable for incorporation of both drugs, whereas alkyl polyglucoside-based systems did not exhibit satisfying solubilization capacity for sertaconazole nitrate. Further, monitored parameters were strongly affected by sertaconazole nitrate incorporation, while they remained almost unchanged in adapalene-loaded vehicles. In addition, results of the in vivo skin performance study supported acceptable tolerability for all investigated formulations, suggesting selected microemulsions as promising carriers worth exploring further for effective skin delivery of model drugs.
PB  - Hrvatsko Farmaceutsko Drustov (HFD)-Croation Pharmaceutical Soc, Zagreb
T2  - Acta Pharmaceutica
T1  - Alkyl polyglucoside vs. ethoxylated surfactant-based microemulsions as vehicles for two poorly water-soluble drugs: physicochemical characterization and in vivo skin performance
VL  - 67
IS  - 4
SP  - 415
EP  - 439
DO  - 10.1515/acph-2017-0036
ER  - 

@article{
author = "Bubić-Pajić, Nataša and Todosijević, Marija N. and Vuleta, Gordana and Cekić, Nebojša and Dobričić, Vladimir and Vučen, Sonja and Čalija, Bojan and Lukić, Milica and Ilić, Tanja and Savić, Snežana",
year = "2017",
abstract = "Two types of biocompatible surfactants were evaluated for their capability to formulate skin-friendly/non-irritant microemulsions as vehicles for two poorly water-soluble model drugs differing in properties and concentrations: alkyl polyglucosides (decyl glucoside and caprylyl/capryl glucoside) and ethoxylated surfactants (glycereth-7-caprylate/caprate and polysorbate 80). Phase behavior, structural inversion and microemulsion solubilization potential for sertaconazole nitrate and adapalene were found to be highly dependent on the surfactants structure and HLB value. Performed characterization (polarized light microscopy, pH, electrical conductivity, rheological, FTIR and DSC measurements) indicated a formulation containing glycereth-7-caprylate/caprate as suitable for incorporation of both drugs, whereas alkyl polyglucoside-based systems did not exhibit satisfying solubilization capacity for sertaconazole nitrate. Further, monitored parameters were strongly affected by sertaconazole nitrate incorporation, while they remained almost unchanged in adapalene-loaded vehicles. In addition, results of the in vivo skin performance study supported acceptable tolerability for all investigated formulations, suggesting selected microemulsions as promising carriers worth exploring further for effective skin delivery of model drugs.",
publisher = "Hrvatsko Farmaceutsko Drustov (HFD)-Croation Pharmaceutical Soc, Zagreb",
journal = "Acta Pharmaceutica",
title = "Alkyl polyglucoside vs. ethoxylated surfactant-based microemulsions as vehicles for two poorly water-soluble drugs: physicochemical characterization and in vivo skin performance",
volume = "67",
number = "4",
pages = "415-439",
doi = "10.1515/acph-2017-0036"
}

Bubić-Pajić, N., Todosijević, M. N., Vuleta, G., Cekić, N., Dobričić, V., Vučen, S., Čalija, B., Lukić, M., Ilić, T.,& Savić, S.. (2017). Alkyl polyglucoside vs. ethoxylated surfactant-based microemulsions as vehicles for two poorly water-soluble drugs: physicochemical characterization and in vivo skin performance. in Acta Pharmaceutica
Hrvatsko Farmaceutsko Drustov (HFD)-Croation Pharmaceutical Soc, Zagreb., 67(4), 415-439.
https://doi.org/10.1515/acph-2017-0036

Bubić-Pajić N, Todosijević MN, Vuleta G, Cekić N, Dobričić V, Vučen S, Čalija B, Lukić M, Ilić T, Savić S. Alkyl polyglucoside vs. ethoxylated surfactant-based microemulsions as vehicles for two poorly water-soluble drugs: physicochemical characterization and in vivo skin performance. in Acta Pharmaceutica. 2017;67(4):415-439.
doi:10.1515/acph-2017-0036 .

Bubić-Pajić, Nataša, Todosijević, Marija N., Vuleta, Gordana, Cekić, Nebojša, Dobričić, Vladimir, Vučen, Sonja, Čalija, Bojan, Lukić, Milica, Ilić, Tanja, Savić, Snežana, "Alkyl polyglucoside vs. ethoxylated surfactant-based microemulsions as vehicles for two poorly water-soluble drugs: physicochemical characterization and in vivo skin performance" in Acta Pharmaceutica, 67, no. 4 (2017):415-439,
https://doi.org/10.1515/acph-2017-0036 . .

TY  - JOUR
AU  - Dobričić, Vladimir
AU  - Bubić-Pajić, Nataša
AU  - Marković, Bojan
AU  - Vladimirov, Sote
AU  - Savić, Snežana
AU  - Vuleta, Gordana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2627
AB  - The development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of adapalene in pharmaceutical forms for skin application were presented in this study. The MS/MS analysis of adapalene was performed by use of three mobile phases, consisted of acetonitrile and a) 0.1 % formic acid, b) 0.1 % trifluoroacetic acid and c) 20 mM ammonium acetate. The strongest signals of parent ion and dominant product ion were obtained in negative mode by use of the mobile phase c). The validation of this method was performed according to the ICH guidelines. Small variations of selected chromatographic parameters (concentration of ammonium acetate, mobile phase composition, column temperature and flow rate) did not affect significantly the qualitative and quantitative system responses, which proved the method's robustness. The method is specific for the determination of adapalene. The linearity was proved in the concentration range of 6.7-700.0 ng mL(-1) (r = 0.9990), with limits of detection and quantification of 2.0 and 6.7 ng mL(-1), respectively. The accuracy was confirmed by calculated recoveries (98.4-101.5 %). The precision was tested at three levels: injection repeatability, analysis repeatability and intermediate precision. The calculated relative standard deviations were less than 1, 2 and 3 %, respectively.
PB  - Srpsko hemijsko društvo, Beograd
T2  - Journal of the Serbian Chemical Society
T1  - Development and validation of an LC-MS/MS method for the determination of adapalene in pharmaceutical forms for skin application
VL  - 81
IS  - 10
SP  - 1171
EP  - 1181
DO  - 10.2298/JSC160215066D
ER  - 

@article{
author = "Dobričić, Vladimir and Bubić-Pajić, Nataša and Marković, Bojan and Vladimirov, Sote and Savić, Snežana and Vuleta, Gordana",
year = "2016",
abstract = "The development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of adapalene in pharmaceutical forms for skin application were presented in this study. The MS/MS analysis of adapalene was performed by use of three mobile phases, consisted of acetonitrile and a) 0.1 % formic acid, b) 0.1 % trifluoroacetic acid and c) 20 mM ammonium acetate. The strongest signals of parent ion and dominant product ion were obtained in negative mode by use of the mobile phase c). The validation of this method was performed according to the ICH guidelines. Small variations of selected chromatographic parameters (concentration of ammonium acetate, mobile phase composition, column temperature and flow rate) did not affect significantly the qualitative and quantitative system responses, which proved the method's robustness. The method is specific for the determination of adapalene. The linearity was proved in the concentration range of 6.7-700.0 ng mL(-1) (r = 0.9990), with limits of detection and quantification of 2.0 and 6.7 ng mL(-1), respectively. The accuracy was confirmed by calculated recoveries (98.4-101.5 %). The precision was tested at three levels: injection repeatability, analysis repeatability and intermediate precision. The calculated relative standard deviations were less than 1, 2 and 3 %, respectively.",
publisher = "Srpsko hemijsko društvo, Beograd",
journal = "Journal of the Serbian Chemical Society",
title = "Development and validation of an LC-MS/MS method for the determination of adapalene in pharmaceutical forms for skin application",
volume = "81",
number = "10",
pages = "1171-1181",
doi = "10.2298/JSC160215066D"
}

Dobričić, V., Bubić-Pajić, N., Marković, B., Vladimirov, S., Savić, S.,& Vuleta, G.. (2016). Development and validation of an LC-MS/MS method for the determination of adapalene in pharmaceutical forms for skin application. in Journal of the Serbian Chemical Society
Srpsko hemijsko društvo, Beograd., 81(10), 1171-1181.
https://doi.org/10.2298/JSC160215066D

Dobričić V, Bubić-Pajić N, Marković B, Vladimirov S, Savić S, Vuleta G. Development and validation of an LC-MS/MS method for the determination of adapalene in pharmaceutical forms for skin application. in Journal of the Serbian Chemical Society. 2016;81(10):1171-1181.
doi:10.2298/JSC160215066D .

Dobričić, Vladimir, Bubić-Pajić, Nataša, Marković, Bojan, Vladimirov, Sote, Savić, Snežana, Vuleta, Gordana, "Development and validation of an LC-MS/MS method for the determination of adapalene in pharmaceutical forms for skin application" in Journal of the Serbian Chemical Society, 81, no. 10 (2016):1171-1181,
https://doi.org/10.2298/JSC160215066D . .

TY  - JOUR
AU  - Vučen, Sonja
AU  - Bubić-Pajić, Nataša
AU  - Savić, Snežana
AU  - Vuleta, Gordana
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2273
AB  - The efficiency of(trans)dermal drug delivery has been severely reduced by the inability of most drugs to penetrate the skin at therapeutically useful rates. Recently, the use of micron-scale needles has been shown to increase skin permeability and significantly improve (trans)dermal drug delivery, particularly for macromolecules. Using the tools of the microelectronics industry and different materials, microneedles of various sizes and shapes have been fabricated. Due to their micron size (less than 300 μm in diameter and 50-900 μm in length), these needles do not reach the nerve endings in the dermis, providing a painless application, which is considered as their main advantage over hypodermic needles. Pathways created using microneedles are orders of magnitude bigger than molecular dimensions and, therefore, should readily permit transport of macromolecules, as well as possibly supramolecular complexes and microparticles Recently, in vivo studies have demonstrated a successful delivery of oligonucleotides, insulin, and many other drugs using a microneedles, as well as induction of the immune response from protein and DNA vaccines. Numerous studies conducted in this research field have led to launching the first microneedle-based (trans)dermal drug delivery systems on the market.
AB  - Efikasnost terapijskih sistema za (trans)dermalnu isporuku lijekova je u znatnoj mjeri umanjena zbog otežanog prolaska lijekova u/kroz kožu. Nedavno je pokazano da je upotrebom igala mikronskih veličina moguće povećati permeabilnost kože i znatno poboljšati (trans)dermalnu isporuku, naročito u slučaju makromolekula. Primjenom dostignuća mikroelektronske industrije, od različitih materijala su proizvedene mikroigle različitih veličina i oblika. S obzirom na svoje mikronske veličine (prečnika obično oko 1 μm i dužine 50-900 μm), ovakve igle ne dopiru do nervnih završetaka u dermisu, čime obezbjeđuju bezbolnu primjenu, što se smatra njihovom osnovnom prednošću u odnosu na potkožne igle. Nastale pore u koži su nekoliko puta veće od dimenzija molekula, te je omogućen transport makromolekula, kao i supramolekularnih kompleksa i nano/mikročestica. Dosadašnje in vivo studije su pokazale uspješnu (trans)dermalnu isporuku oligonukleotida, insulina i drugih lijekova primjenom mikroigala, kao i indukciju imunskog odgovora proteinskim i DNK vakcinama. Brojni radovi sprovedeni u ovoj oblasti istraživanja doveli su i do pojave na tržištu prvih sistema za (trans)dermalnu isporuku lijekova zasnovanih na tehnologiji mikroigala.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Microneedles: Physical enhancers for (trans)dermal drug delivery
T1  - Mikroigle - fizički pojačivači (trans)dermalne isporuke lijekova
VL  - 64
IS  - 4
SP  - 295
EP  - 321
DO  - 10.5937/arhfarm1404295V
ER  - 

@article{
author = "Vučen, Sonja and Bubić-Pajić, Nataša and Savić, Snežana and Vuleta, Gordana",
year = "2014",
abstract = "The efficiency of(trans)dermal drug delivery has been severely reduced by the inability of most drugs to penetrate the skin at therapeutically useful rates. Recently, the use of micron-scale needles has been shown to increase skin permeability and significantly improve (trans)dermal drug delivery, particularly for macromolecules. Using the tools of the microelectronics industry and different materials, microneedles of various sizes and shapes have been fabricated. Due to their micron size (less than 300 μm in diameter and 50-900 μm in length), these needles do not reach the nerve endings in the dermis, providing a painless application, which is considered as their main advantage over hypodermic needles. Pathways created using microneedles are orders of magnitude bigger than molecular dimensions and, therefore, should readily permit transport of macromolecules, as well as possibly supramolecular complexes and microparticles Recently, in vivo studies have demonstrated a successful delivery of oligonucleotides, insulin, and many other drugs using a microneedles, as well as induction of the immune response from protein and DNA vaccines. Numerous studies conducted in this research field have led to launching the first microneedle-based (trans)dermal drug delivery systems on the market., Efikasnost terapijskih sistema za (trans)dermalnu isporuku lijekova je u znatnoj mjeri umanjena zbog otežanog prolaska lijekova u/kroz kožu. Nedavno je pokazano da je upotrebom igala mikronskih veličina moguće povećati permeabilnost kože i znatno poboljšati (trans)dermalnu isporuku, naročito u slučaju makromolekula. Primjenom dostignuća mikroelektronske industrije, od različitih materijala su proizvedene mikroigle različitih veličina i oblika. S obzirom na svoje mikronske veličine (prečnika obično oko 1 μm i dužine 50-900 μm), ovakve igle ne dopiru do nervnih završetaka u dermisu, čime obezbjeđuju bezbolnu primjenu, što se smatra njihovom osnovnom prednošću u odnosu na potkožne igle. Nastale pore u koži su nekoliko puta veće od dimenzija molekula, te je omogućen transport makromolekula, kao i supramolekularnih kompleksa i nano/mikročestica. Dosadašnje in vivo studije su pokazale uspješnu (trans)dermalnu isporuku oligonukleotida, insulina i drugih lijekova primjenom mikroigala, kao i indukciju imunskog odgovora proteinskim i DNK vakcinama. Brojni radovi sprovedeni u ovoj oblasti istraživanja doveli su i do pojave na tržištu prvih sistema za (trans)dermalnu isporuku lijekova zasnovanih na tehnologiji mikroigala.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Microneedles: Physical enhancers for (trans)dermal drug delivery, Mikroigle - fizički pojačivači (trans)dermalne isporuke lijekova",
volume = "64",
number = "4",
pages = "295-321",
doi = "10.5937/arhfarm1404295V"
}

Vučen, S., Bubić-Pajić, N., Savić, S.,& Vuleta, G.. (2014). Microneedles: Physical enhancers for (trans)dermal drug delivery. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 64(4), 295-321.
https://doi.org/10.5937/arhfarm1404295V

Vučen S, Bubić-Pajić N, Savić S, Vuleta G. Microneedles: Physical enhancers for (trans)dermal drug delivery. in Arhiv za farmaciju. 2014;64(4):295-321.
doi:10.5937/arhfarm1404295V .

Vučen, Sonja, Bubić-Pajić, Nataša, Savić, Snežana, Vuleta, Gordana, "Microneedles: Physical enhancers for (trans)dermal drug delivery" in Arhiv za farmaciju, 64, no. 4 (2014):295-321,
https://doi.org/10.5937/arhfarm1404295V . .

TY  - JOUR
AU  - Bubić-Pajić, Nataša
AU  - Pantelić, Ivana
AU  - Savić, Snežana
AU  - Vuleta, Gordana
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1777
AB  - Many drugs used for the treatment of babies and children are not available in the market in dosage forms appropriate for this population. Moreover, a considerable number of these drugs are not registered for pediatric use. Since liquid oral dosage forms are considered most acceptable for children, if not available in the market, they can be extemporaneously prepared from available registered drug preparations. Preparation of such liquid oral dosage forms from solid dosage forms demands meticulous consideration of many factors, such as physicochemical characteristics of both active substances and excipients, along with drug-excipient and excipient-excipient compatibility. When deciding on a formulation, the one with literature background concerning stability data, recommended expiry date, expected bioavailability, efficacy and tolerability of the ex tempore prepared drug should preferably be selected. Many regulatory bodies have recognized the importance of these issues, and introduced suitable guidelines such as Regulation of the EU No 1901/2006 that became mandatory on 1.1.2007., with the purpose to make pediatric drugs more available, as well as to ascertain the preparation of drugs of outmost quality, having in mind that extemporaneous drugs are not submitted through preclinical and clinical trails.
AB  - Mnogi lekovi koji se koriste za lečenje beba i dece nisu dostupni na tržištu u farmaceutskom obliku koji je pogodan za primenu kod ove populacije pacijenata. Štaviše, veći broj ovih lekova nije registrovan za upotrebu kod pedijatrijske grupe pacijenata. S obzirom da deca najbolje prihvataju tečne farmaceutske preparate za peroralnu primenu, ukoliko nisu dostupni na tržištu lekova, mogu se pripremati ex tempore za pojedinačnog pacijenta iz dostupnih registrovanih lekova. Izrada tečnih farmaceutskih oblika za peroralnu primenu iz čvrstih farmaceutskih oblika zahteva pažljivo razmatranje mnogih faktora, kao što su fizičkohemijske osobine aktivnih i pomoćnih supstanci i kompatibilnost lekovitih supstanci sa ekscipijensima, ali i kompatibilnost pomoćnih materija međusobno. Kod izbora formulacije, uvek treba da se odabere ona za koju u stručnoj literaturi postoje podaci o stabilnosti preparata, eventualno i roku upotrebe, biološkoj raspoloživosti, efikasnosti i podnošljivosti leka koji je izrađen ex tempore. U ova nastojanja uključila su se i brojna ovlašćena tela donošenjem odgovarajućih dokumenata, poput Uredbe EU broj 1901/2006 koja je stupila na snagu 1.1.2007. godine, sa ciljem da se lekovi za pedijatrijsku populaciju učine dostupnijim, kao i da se osigura izrada lekova najvišeg kvaliteta s obzirom da ex tempore izrađeni lekovi ne prolaze kroz pretkliničke i kliničke studije.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Liquid extemporaneous pharmaceutical preparations for pediatric patients
T1  - Tečni farmaceutski preparati za primenu u pedijatriji izrađeni ex tempore
VL  - 62
IS  - 3
SP  - 252
EP  - 266
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1777
ER  - 

@article{
author = "Bubić-Pajić, Nataša and Pantelić, Ivana and Savić, Snežana and Vuleta, Gordana",
year = "2012",
abstract = "Many drugs used for the treatment of babies and children are not available in the market in dosage forms appropriate for this population. Moreover, a considerable number of these drugs are not registered for pediatric use. Since liquid oral dosage forms are considered most acceptable for children, if not available in the market, they can be extemporaneously prepared from available registered drug preparations. Preparation of such liquid oral dosage forms from solid dosage forms demands meticulous consideration of many factors, such as physicochemical characteristics of both active substances and excipients, along with drug-excipient and excipient-excipient compatibility. When deciding on a formulation, the one with literature background concerning stability data, recommended expiry date, expected bioavailability, efficacy and tolerability of the ex tempore prepared drug should preferably be selected. Many regulatory bodies have recognized the importance of these issues, and introduced suitable guidelines such as Regulation of the EU No 1901/2006 that became mandatory on 1.1.2007., with the purpose to make pediatric drugs more available, as well as to ascertain the preparation of drugs of outmost quality, having in mind that extemporaneous drugs are not submitted through preclinical and clinical trails., Mnogi lekovi koji se koriste za lečenje beba i dece nisu dostupni na tržištu u farmaceutskom obliku koji je pogodan za primenu kod ove populacije pacijenata. Štaviše, veći broj ovih lekova nije registrovan za upotrebu kod pedijatrijske grupe pacijenata. S obzirom da deca najbolje prihvataju tečne farmaceutske preparate za peroralnu primenu, ukoliko nisu dostupni na tržištu lekova, mogu se pripremati ex tempore za pojedinačnog pacijenta iz dostupnih registrovanih lekova. Izrada tečnih farmaceutskih oblika za peroralnu primenu iz čvrstih farmaceutskih oblika zahteva pažljivo razmatranje mnogih faktora, kao što su fizičkohemijske osobine aktivnih i pomoćnih supstanci i kompatibilnost lekovitih supstanci sa ekscipijensima, ali i kompatibilnost pomoćnih materija međusobno. Kod izbora formulacije, uvek treba da se odabere ona za koju u stručnoj literaturi postoje podaci o stabilnosti preparata, eventualno i roku upotrebe, biološkoj raspoloživosti, efikasnosti i podnošljivosti leka koji je izrađen ex tempore. U ova nastojanja uključila su se i brojna ovlašćena tela donošenjem odgovarajućih dokumenata, poput Uredbe EU broj 1901/2006 koja je stupila na snagu 1.1.2007. godine, sa ciljem da se lekovi za pedijatrijsku populaciju učine dostupnijim, kao i da se osigura izrada lekova najvišeg kvaliteta s obzirom da ex tempore izrađeni lekovi ne prolaze kroz pretkliničke i kliničke studije.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Liquid extemporaneous pharmaceutical preparations for pediatric patients, Tečni farmaceutski preparati za primenu u pedijatriji izrađeni ex tempore",
volume = "62",
number = "3",
pages = "252-266",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1777"
}

Bubić-Pajić, N., Pantelić, I., Savić, S.,& Vuleta, G.. (2012). Liquid extemporaneous pharmaceutical preparations for pediatric patients. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 62(3), 252-266.
https://hdl.handle.net/21.15107/rcub_farfar_1777

Bubić-Pajić N, Pantelić I, Savić S, Vuleta G. Liquid extemporaneous pharmaceutical preparations for pediatric patients. in Arhiv za farmaciju. 2012;62(3):252-266.
https://hdl.handle.net/21.15107/rcub_farfar_1777 .

Bubić-Pajić, Nataša, Pantelić, Ivana, Savić, Snežana, Vuleta, Gordana, "Liquid extemporaneous pharmaceutical preparations for pediatric patients" in Arhiv za farmaciju, 62, no. 3 (2012):252-266,
https://hdl.handle.net/21.15107/rcub_farfar_1777 .