Dermalna raspoloživost lekova sa antiinflamatornim delovanjem iz podloga sa šećernim emulgatorom : komparativna primena in vitro / in vivo karakterizacije
Dermal bioavailability of antiinflammatory drugs from sugar emulsifier stabilized bases: comparative application of in vitro / in vivo characterization methods
Аутори
Pantelić, IvanaОстала ауторства
Savić, SnežanaMilić, Jela
Vuleta, Gordana
Daniels, Rolf
Vesić, Sonja
Докторска теза (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Uvod Aktuelna farmakoekonomska situacija ima za posledicu čest nedostataklekova u potrebnim dozama/jačinama, a za neke lekovite supstance nisu odabranipogodni nosači. Značaj primene odgovarajućeg vehikuluma/podloge naročito je izraženu slučaju lekova koji se primenjuju na koži. Ova grupa lekova podložna je i uticajimakoji dolaze iz kozmetičke industrije, a odnose se na zadovoljavajući izgled, teksturu isenzorne karakteristike nosača, što se direktno reflektuje u kojoj meri će se pacijentipridržavati propisanoj terapiji. Nedostatak lekova na tržištu može se prevazići izradomlekova u apoteci čime se, čak i u zemljama sa veoma razvijenom farmaceutskomindustrijom, ponovo potencira značaj znanja i veština farmaceuta u ex tempore izradilekova. Iz tog razloga, prepoznata je potreba za inoviranjem sastava takvih lekova, presvega uvođenjem formulacija sa savremenim farmaceutskim ekscipijensima. S drugestrane, ostaje otvoreno pitanje procene dermalne raspoloživosti ovakvih lekova, sobzirom da re...gulatorno prihvaćene metode nisu univerzalno primenljive (poputograničene primenljivosti vazokonstriktornog testa na lekove iz grupe kortikosteroida)ili se smatraju neracionalnim u fazi razvoja formulacije (podrazumevaju značajnaulaganja i veliki broj ispitanika).Cilj istraživanja Cilj istraživanja ove disertacije bio je razvoj formulacije,fizičkohemijska i biofarmaceutska karakterizacija emulzionih sistema (podloga)stabilizovanih prirodnim mešanim emulgatorom tipa alkil poliglukozida (APG), sastavacetostearil glukozid i cetostearil alkohol, koji je od skora sertificiran kao farmaceutskiekscipijens. Razvijene formulacije poslužile su kao modeli za razvoj i optimizacijuprotokola metode sa adhezivnim trakama (tape stripping metode) kao perspektivne invivo tehnike za ispitivanje penetracije lekova kroz kožu, uz sprovođenje korelacije datihrezultata sa onim dobijenim prihvaćenim in vitro i in vivo metodama kroz nekolikostudija slučaja (ketoprofen, diklofenak dietilamin i hidrokortizon kao model lekovitesupstance sa antiinflamatornim delovanjem, različitih fizičkohemijskih karakteristika)...
Introduction Current pharmacoeconomic situation has resulted in a frequent shortagein certain drug doses/strengths or suitable dosage forms. The importance of theappropriate choice of the vehicle/base is especially emphasized in case of topical drugs.These are prone to influences stemming from the cosmetic industry, relating tosatisfactory appearance, texture and sensorial properties of the carrier, which directlyreflects patient adherence. Such drug deficiencies may be overcome throughcompounding practice in pharmacies which is, even in countries with highly developedpharmaceutical industry, reevaluating the importance of pharmacist’s knowledge andskills in extemporaneous drug preparation. Therefore, there is a need to innovate thecomposition of such drugs, particularly via introduction of formulations based on novelpharmaceutical excipients. On the other hand, the issue of dermal bioavailabilityassessment of these drugs remains, considering the regulatory accepted methods are notuniv...ersally applicable (use of the skin blanching assay is limited to corticosteroid drugs)or their use is irrational in the formulation development phase (require substantial fundsand a large number of volunteers).Aim The aim of this work was the development, physicochemical andbiopharmaceutical characterization of emulsion systems (bases) stabilized with naturaloriginmixed alkyl polyglucoside (APG) emulsifier comprising cetostearyl glucosideand cetostearyl alcohol, recently given a status of pharmaceutical excipient. Theseformulations served as models for development and optimization of the tape strippingmethod protocol that could serve as a prospective in vivo technique for skin penetrationstudies, along with correlation of the obtained results with those provided through theacknowledged in vitro and in vivo methods via several case-studies (ketoprofen,diclofenac diethylamine and hydrocortisone as anti-inflammatory model drugs withdiverse physicochemical characteristics).Methods Experimental work was organized in three phases: 1) With the aim ofassessing physical stability and colloidal structure of the model bases stabilized with thesugar emulsifier, a comprehensive characterization was performed using polarization microscopy, pH and conductivity measurements, saturation concentration of modeldrugs, continual rheology, differential scanning calorimetry, thermogravimetricanalysis, in vitro screening of model drugs liberation profiles, assessing the safetyprofiles of model bases: in vitro – citotoxicity assay and in vivo – non-invasive skinbioengineering techniques...
Кључне речи:
Alkil poliglukozidni emulgatori / Alkyl polyglucoside emulsifiers / lamelarni tečni kristali / podloge za extempore izradu kremova / ketoprofen / diklofenak dietilamin / hidrokortizon / metoda saadhezivnim trakama / vazokonstriktorni test / veštački konstrukti kože / izolovani stratum corneum / lamellar liquid crystals / drugcompounding/extemporaneous drug preparation / ketoprofen / diclofenac diethylamine / hydrocortisone / tape stripping method / skin blanching assay / artificial skin constructs / isolated stratum corneumИзвор:
Универзитет у Београду, 2013Издавач:
- Универзитет у Београду, Фармацеутски факултет
Финансирање / пројекти:
- Развој микро- и наносистема као носача за лекове са антиинфламаторним деловањем и метода за њихову карактеризацију (RS-MESTD-Technological Development (TD or TR)-34031)
URI
http://eteze.bg.ac.rs/application/showtheses?thesesId=1016https://fedorabg.bg.ac.rs/fedora/get/o:7657/bdef:Content/download
http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=45081359
http://nardus.mpn.gov.rs/123456789/3153
https://farfar.pharmacy.bg.ac.rs/handle/123456789/3405
Колекције
Институција/група
PharmacyTY - THES AU - Pantelić, Ivana PY - 2013 UR - http://eteze.bg.ac.rs/application/showtheses?thesesId=1016 UR - https://fedorabg.bg.ac.rs/fedora/get/o:7657/bdef:Content/download UR - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=45081359 UR - http://nardus.mpn.gov.rs/123456789/3153 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3405 AB - Uvod Aktuelna farmakoekonomska situacija ima za posledicu čest nedostataklekova u potrebnim dozama/jačinama, a za neke lekovite supstance nisu odabranipogodni nosači. Značaj primene odgovarajućeg vehikuluma/podloge naročito je izraženu slučaju lekova koji se primenjuju na koži. Ova grupa lekova podložna je i uticajimakoji dolaze iz kozmetičke industrije, a odnose se na zadovoljavajući izgled, teksturu isenzorne karakteristike nosača, što se direktno reflektuje u kojoj meri će se pacijentipridržavati propisanoj terapiji. Nedostatak lekova na tržištu može se prevazići izradomlekova u apoteci čime se, čak i u zemljama sa veoma razvijenom farmaceutskomindustrijom, ponovo potencira značaj znanja i veština farmaceuta u ex tempore izradilekova. Iz tog razloga, prepoznata je potreba za inoviranjem sastava takvih lekova, presvega uvođenjem formulacija sa savremenim farmaceutskim ekscipijensima. S drugestrane, ostaje otvoreno pitanje procene dermalne raspoloživosti ovakvih lekova, sobzirom da regulatorno prihvaćene metode nisu univerzalno primenljive (poputograničene primenljivosti vazokonstriktornog testa na lekove iz grupe kortikosteroida)ili se smatraju neracionalnim u fazi razvoja formulacije (podrazumevaju značajnaulaganja i veliki broj ispitanika).Cilj istraživanja Cilj istraživanja ove disertacije bio je razvoj formulacije,fizičkohemijska i biofarmaceutska karakterizacija emulzionih sistema (podloga)stabilizovanih prirodnim mešanim emulgatorom tipa alkil poliglukozida (APG), sastavacetostearil glukozid i cetostearil alkohol, koji je od skora sertificiran kao farmaceutskiekscipijens. Razvijene formulacije poslužile su kao modeli za razvoj i optimizacijuprotokola metode sa adhezivnim trakama (tape stripping metode) kao perspektivne invivo tehnike za ispitivanje penetracije lekova kroz kožu, uz sprovođenje korelacije datihrezultata sa onim dobijenim prihvaćenim in vitro i in vivo metodama kroz nekolikostudija slučaja (ketoprofen, diklofenak dietilamin i hidrokortizon kao model lekovitesupstance sa antiinflamatornim delovanjem, različitih fizičkohemijskih karakteristika)... AB - Introduction Current pharmacoeconomic situation has resulted in a frequent shortagein certain drug doses/strengths or suitable dosage forms. The importance of theappropriate choice of the vehicle/base is especially emphasized in case of topical drugs.These are prone to influences stemming from the cosmetic industry, relating tosatisfactory appearance, texture and sensorial properties of the carrier, which directlyreflects patient adherence. Such drug deficiencies may be overcome throughcompounding practice in pharmacies which is, even in countries with highly developedpharmaceutical industry, reevaluating the importance of pharmacist’s knowledge andskills in extemporaneous drug preparation. Therefore, there is a need to innovate thecomposition of such drugs, particularly via introduction of formulations based on novelpharmaceutical excipients. On the other hand, the issue of dermal bioavailabilityassessment of these drugs remains, considering the regulatory accepted methods are notuniversally applicable (use of the skin blanching assay is limited to corticosteroid drugs)or their use is irrational in the formulation development phase (require substantial fundsand a large number of volunteers).Aim The aim of this work was the development, physicochemical andbiopharmaceutical characterization of emulsion systems (bases) stabilized with naturaloriginmixed alkyl polyglucoside (APG) emulsifier comprising cetostearyl glucosideand cetostearyl alcohol, recently given a status of pharmaceutical excipient. Theseformulations served as models for development and optimization of the tape strippingmethod protocol that could serve as a prospective in vivo technique for skin penetrationstudies, along with correlation of the obtained results with those provided through theacknowledged in vitro and in vivo methods via several case-studies (ketoprofen,diclofenac diethylamine and hydrocortisone as anti-inflammatory model drugs withdiverse physicochemical characteristics).Methods Experimental work was organized in three phases: 1) With the aim ofassessing physical stability and colloidal structure of the model bases stabilized with thesugar emulsifier, a comprehensive characterization was performed using polarization microscopy, pH and conductivity measurements, saturation concentration of modeldrugs, continual rheology, differential scanning calorimetry, thermogravimetricanalysis, in vitro screening of model drugs liberation profiles, assessing the safetyprofiles of model bases: in vitro – citotoxicity assay and in vivo – non-invasive skinbioengineering techniques... PB - Универзитет у Београду, Фармацеутски факултет T2 - Универзитет у Београду T1 - Dermalna raspoloživost lekova sa antiinflamatornim delovanjem iz podloga sa šećernim emulgatorom : komparativna primena in vitro / in vivo karakterizacije T1 - Dermal bioavailability of antiinflammatory drugs from sugar emulsifier stabilized bases: comparative application of in vitro / in vivo characterization methods UR - https://hdl.handle.net/21.15107/rcub_nardus_3153 ER -
@phdthesis{ author = "Pantelić, Ivana", year = "2013", abstract = "Uvod Aktuelna farmakoekonomska situacija ima za posledicu čest nedostataklekova u potrebnim dozama/jačinama, a za neke lekovite supstance nisu odabranipogodni nosači. Značaj primene odgovarajućeg vehikuluma/podloge naročito je izraženu slučaju lekova koji se primenjuju na koži. Ova grupa lekova podložna je i uticajimakoji dolaze iz kozmetičke industrije, a odnose se na zadovoljavajući izgled, teksturu isenzorne karakteristike nosača, što se direktno reflektuje u kojoj meri će se pacijentipridržavati propisanoj terapiji. Nedostatak lekova na tržištu može se prevazići izradomlekova u apoteci čime se, čak i u zemljama sa veoma razvijenom farmaceutskomindustrijom, ponovo potencira značaj znanja i veština farmaceuta u ex tempore izradilekova. Iz tog razloga, prepoznata je potreba za inoviranjem sastava takvih lekova, presvega uvođenjem formulacija sa savremenim farmaceutskim ekscipijensima. S drugestrane, ostaje otvoreno pitanje procene dermalne raspoloživosti ovakvih lekova, sobzirom da regulatorno prihvaćene metode nisu univerzalno primenljive (poputograničene primenljivosti vazokonstriktornog testa na lekove iz grupe kortikosteroida)ili se smatraju neracionalnim u fazi razvoja formulacije (podrazumevaju značajnaulaganja i veliki broj ispitanika).Cilj istraživanja Cilj istraživanja ove disertacije bio je razvoj formulacije,fizičkohemijska i biofarmaceutska karakterizacija emulzionih sistema (podloga)stabilizovanih prirodnim mešanim emulgatorom tipa alkil poliglukozida (APG), sastavacetostearil glukozid i cetostearil alkohol, koji je od skora sertificiran kao farmaceutskiekscipijens. Razvijene formulacije poslužile su kao modeli za razvoj i optimizacijuprotokola metode sa adhezivnim trakama (tape stripping metode) kao perspektivne invivo tehnike za ispitivanje penetracije lekova kroz kožu, uz sprovođenje korelacije datihrezultata sa onim dobijenim prihvaćenim in vitro i in vivo metodama kroz nekolikostudija slučaja (ketoprofen, diklofenak dietilamin i hidrokortizon kao model lekovitesupstance sa antiinflamatornim delovanjem, različitih fizičkohemijskih karakteristika)..., Introduction Current pharmacoeconomic situation has resulted in a frequent shortagein certain drug doses/strengths or suitable dosage forms. The importance of theappropriate choice of the vehicle/base is especially emphasized in case of topical drugs.These are prone to influences stemming from the cosmetic industry, relating tosatisfactory appearance, texture and sensorial properties of the carrier, which directlyreflects patient adherence. Such drug deficiencies may be overcome throughcompounding practice in pharmacies which is, even in countries with highly developedpharmaceutical industry, reevaluating the importance of pharmacist’s knowledge andskills in extemporaneous drug preparation. Therefore, there is a need to innovate thecomposition of such drugs, particularly via introduction of formulations based on novelpharmaceutical excipients. On the other hand, the issue of dermal bioavailabilityassessment of these drugs remains, considering the regulatory accepted methods are notuniversally applicable (use of the skin blanching assay is limited to corticosteroid drugs)or their use is irrational in the formulation development phase (require substantial fundsand a large number of volunteers).Aim The aim of this work was the development, physicochemical andbiopharmaceutical characterization of emulsion systems (bases) stabilized with naturaloriginmixed alkyl polyglucoside (APG) emulsifier comprising cetostearyl glucosideand cetostearyl alcohol, recently given a status of pharmaceutical excipient. Theseformulations served as models for development and optimization of the tape strippingmethod protocol that could serve as a prospective in vivo technique for skin penetrationstudies, along with correlation of the obtained results with those provided through theacknowledged in vitro and in vivo methods via several case-studies (ketoprofen,diclofenac diethylamine and hydrocortisone as anti-inflammatory model drugs withdiverse physicochemical characteristics).Methods Experimental work was organized in three phases: 1) With the aim ofassessing physical stability and colloidal structure of the model bases stabilized with thesugar emulsifier, a comprehensive characterization was performed using polarization microscopy, pH and conductivity measurements, saturation concentration of modeldrugs, continual rheology, differential scanning calorimetry, thermogravimetricanalysis, in vitro screening of model drugs liberation profiles, assessing the safetyprofiles of model bases: in vitro – citotoxicity assay and in vivo – non-invasive skinbioengineering techniques...", publisher = "Универзитет у Београду, Фармацеутски факултет", journal = "Универзитет у Београду", title = "Dermalna raspoloživost lekova sa antiinflamatornim delovanjem iz podloga sa šećernim emulgatorom : komparativna primena in vitro / in vivo karakterizacije, Dermal bioavailability of antiinflammatory drugs from sugar emulsifier stabilized bases: comparative application of in vitro / in vivo characterization methods", url = "https://hdl.handle.net/21.15107/rcub_nardus_3153" }
Pantelić, I.. (2013). Dermalna raspoloživost lekova sa antiinflamatornim delovanjem iz podloga sa šećernim emulgatorom : komparativna primena in vitro / in vivo karakterizacije. in Универзитет у Београду Универзитет у Београду, Фармацеутски факултет.. https://hdl.handle.net/21.15107/rcub_nardus_3153
Pantelić I. Dermalna raspoloživost lekova sa antiinflamatornim delovanjem iz podloga sa šećernim emulgatorom : komparativna primena in vitro / in vivo karakterizacije. in Универзитет у Београду. 2013;. https://hdl.handle.net/21.15107/rcub_nardus_3153 .
Pantelić, Ivana, "Dermalna raspoloživost lekova sa antiinflamatornim delovanjem iz podloga sa šećernim emulgatorom : komparativna primena in vitro / in vivo karakterizacije" in Универзитет у Београду (2013), https://hdl.handle.net/21.15107/rcub_nardus_3153 .