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Author:Söderman, Josefin
Title:Release of model drugs with different solubilities from polylactone based degradable polymer matrices
Frigöringshastigheten för läkemedel med varierande lösbarhet från nedbrytbara polylaktonbaserade polymermatriser
Publication type:Master's thesis
Publication year:2012
Pages:vii + 90 s. + liitt. 34      Language:   eng
Department/School:Biotekniikan ja kemian tekniikan laitos
Main subject:Polymeeriteknologia   (Kem-100)
Supervisor:Seppälä, Jukka
Instructor:Korhonen, Harri ; Hakala, Risto
OEVS:
Electronic archive copy is available via Aalto Thesis Database.
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Location:P1 Ark Aalto  1498   | Archive
Keywords:controlled drug delivery
polyester anhydride
poly e-caprolactone-co-lactide
kontrollerad läkemedelsfrigöring
polyester anhydrid
poly e-kaprolakton-co-laktid
Abstract (eng): The aim of this thesis was to study the effect on the release profile of E-caprolactone and L-lactide based polymeric drug delivery devices when active agents of different solubility were used.
Both long-acting and short-acting polymeric drug delivery devices for controlled drug delivery were studied.

For the thesis, the release of three different active agents from two different polymer families was studied in aqueous buffer solution at pH 7.4 and temperature 37°C.
Surface eroding poly(ester-anhydride) samples were prepared by crosslinking functionalised poly(E-caprolactone) precursors, while diffusion controlled the poly(ester) samples were synthesized by ring-opening polymerisation of E-caprolactone and L-lactide.
Two different molar ratios were used for the copolymers.
As active agent's propranolol HCI, amlodipine maleate, and itraconazole were used.
All samples had a 10 m-% drug loading.

The release rate of poly(ester anhydride) samples was linearly related to the erosion rate.
The erosion rate for the samples clearly depended on the hydrophilicity of the active agent so that the most hydrophobic active agent had the slowest degradation time.
All samples degraded in 20 to 35 hours.

In the thermoplastic copolymers, a higher amount of lactide in the copolymer led to a higher release rate.
The difference in release rate due to the molar ratio was most prominent when the active agent was highly hydrophilic.
Depending on the polymer and the active agent, 20 to 100 % of the initial active agent was released during 11 weeks.

This work contributed to the understanding of degradable polymers as drug delivery devices.
Further studies are still needed before the studied materials can be applied for clinical usage.
Also the effect of the testing procedure should be further explored.
Abstract (swe): Syftet med detta diplomarbete var att analysera hur läkemedelsfrigöringen från E-kaprolakton och L-laktid baserade polymerer påverkas av lösligheten hos det använda läkemedlet.
För arbetet tillverkades såväl yteroderande poly(ester anhydrider) med kort frigöringstid (1-2 d), som sampolymerer av E-kaprolakton och L-laktid med avsevärt längre frigöringstid (>3 mån).
Poly(ester anhydriderna) tillverkades genom tvärbindning av funktionaliserade stjärnformade makromerer med korta PCL armar.
Sampolymererna med hög molvikt som främst innehöll E-kaprolakton tillverkades genom bulkpolymerisation.
Tre läkemedel av olika löslighet användes i arbetet.
Alla matriser innehöll 10 v-% läkemedel.
Läkemedelsfrigöringen studerades i vattenlösning med pH 7,4 och temperaturen 37°C.

För poly(ester anhydriderna) var frigöringshastigheten linjärt proportionell till erosionshastigheten, som i sin tur påverkades av läkemedlets hydrofilitet så att sampel med ett hydrofilt läkemedel sönderföll avsevärt snabbare än sampel innehållandes ett mer hydrofobt läkemedel.
Även hos termoplasterna frigavs hydrofila läkemedel snabbare än hydrofoba.
Termoplasten med en högre andel laktid hade en högre frigöringshastighet.
Denna skillnad var mest prominent för det hydrofila läkemedlet, medan effekten var i knappt märkbar för det mest hydrofoba läkemedlet.

Det kan konstateras att läkemedlets lösbarhet märkbart påverkar frigöringshastigheten.
Arbetet har bidragit till den allmänna förståelsen om dessa polymerer, men fler studier behövs innan materialen kan tas i kliniskt bruk.
Effekten av den valda forskningsmetoden bör studeras ytterligare, i synnerhet då det gäller hydrofoba läkemedel.
ED:2012-05-23
INSSI record number: 44623
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