Stabilnost kitozanskih i poloksamersko-kitozanskih mikrosfera s melatoninom pripravljenih sušenjem raspršivanjem

master's thesis

• Title (english): Stability of melatonin-loaded chitosan and poloxamer/chitosan microspheres prepared by spray-drying method
• Author: Anja Đakmanec
• Mentor: Anita Hafner (mentor)
• Committee member: Anita Hafner (predsjednik povjerenstva)
• Committee member: Mario Jug (član povjerenstva)
• Committee member: Dubravka Vitali Čepo (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical technology); Zagreb
• Defense date and country: 2017-09-29, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Mikrosfere temeljene na kitozanu intenzivno se istražuju kao mukoadhezivni terapijski sustavi kontroliranog oslobađanja lijeka. Često se pripravljaju tehnikom sušenja raspršivanjem, koja omogućuje pripremu mikročestica željenih fizičko-kemijskih svojstava. Stabilnost mikročestica uvjetovana je svojstvima djelatne i pomoćnih tvari iz kojih su građene, ali i samim procesom formiranja čestica tijekom sušenja raspršivanjem, što je potrebno uzeti u obzir pri razvoju stabilnog produkta.
U ovom radu pripravljene su kitozanske i poloksamersko-kitozanske mikrosfere s melatoninom prethodno optimiranom metodom sušenja raspršivanjem. lavni cilj ovog rada bio je ispitati stabilnost pripravljenih mikrosfera u ovisnosti o njihovom sastavu i uvjetima skladištenja. Mikrosfere su skladištene pri temperaturi od 4-8°C te pri temperaturi od 25°C i relativnoj vlažnosti od 60%. Stabilnost mikrosfera procijenjena je praćenjem srednjeg geometrijskog promjera, raspodjele veličine i površinskog naboja tijekom šestomjesečnog skladištenja, dok je sadržaj uklopljenog lijeka određen nakon šestomjesečnog i dvogodišnjeg skladištenja. Mikrosfere su karakterizirane prosječnom veličinom čestica od 2,5 do 2,8 μm, zeta-potencijalom od 29 do 34 mV, te velikom uspješnošću uklapanja melatonina ( 99,5 %). Pripravljene kitozanske i poloksamersko-kitozanske mikrosfere imale su zadovoljavajući sadržaj melatonina od 33,2 ± 0,2 %, odnosno 29,4 ± 1,2 %. Kitozanske mikrosfere s melatoninom zadržale su fizička svojstva tijekom šestomjesečnog skladištenja pri temperaturi od 4-8°C dok je pri temperaturi od 25°C i relativnoj vlažnosti od 60% uočen blagi pad zeta-potencijala. Poloksamersko-kitozanske mikrosfere s melatoninom zadržale su fizička svojstva tijekom šestomjesečnog skladištenja neovisno o uvjetima skladištenja. Stabilnost mikrosfera s obzirom na sadržaj lijeka ovisila je o sastavu mikrosfera, ali ne i o uvjetima čuvanja. Sadržaj uklopljenog lijeka u poloksamersko-kitozanske mikrosfere ostao je očuvan i nakon šestomjesečnog i nakon dvogodišnjeg skladištenja pri temperaturi od 4-8°C te pri temperaturi od 25°C i relativnoj vlažnosti od 60%, dok je u slučaju kitozanskih mikrosfera zabilježen blagi pad u sadržaju lijeka nakon dvogodišnjeg skladištenja pri istim uvjetima. Rezultati provedenog ispitivanja upućuju na veću stabilnost poloksamersko-kitozanskih mikrosfera s melatoninom u odnosu na kitozanske mikrosfere s istim lijekom.

Abstract (english)

Chitosan-based microspheres have been extensively studied as mucoadhesive and controlled release drug delivery systems. One of the mostly used methods for their preparation is the spray-drying method, which allows for the creation of microparticles of desired physical-chemical properties. The stability of microparticles not only depends on the properties of the active pharmaceutical ingredient and excipients as microparticle constituents, but also on the particle-forming process during the spray drying, which should be taken into consideration when developing a stable product.
In this study, melatonin-loaded chitosan and poloxamer/chitosan microspheres were prepared using the previously optimised spray-drying method. The aim of this study was to test the stability of the prepared microspheres in relation to their composition and storage conditions. Microspheres were stored at the temperature of 4-8°C, and at the temperature of 25°C and relative humidity of 60%. The stability of microspheres was evaluated by monitoring the microsphere mean geometric diameter, size distribution and surface charge over six-month period and determining the content of the drug entrapped after 6-month and 2-year period of storage. Microspheres were characterised by mean diameter ranging between 2.5 and 2.8 μm, zeta-potential ranging between 29 and 34mV and high melatonin entrapment efficiency ( 99.5 %). The drug content in the chitosan and poloxamer/chitosan microspheres prepared was 33.2 ± 0.2% and 29.4 ± 1.2%, respectively. Melatonin-loaded chitosan microspheres preserved their physical properties during the six-month storage at the temperature of 4-8°C, while a mild decrease in zeta-potential was observed at a temperature of 25°C and the relative humidity of 60%. Melatonin-loaded poloxamer/chitosan microspheres preserved their physical properties during the six-month storage regardless of the storage conditions. Microsphere stability in terms of drug content depended on microsphere composition rather than storage conditions. Drug content in poloxamer/chitosan microspheres remained unchanged after 6-months and 2-years of storage at temperature of 4-8°C as well as at temperature of 25°C and relative humidity of 60%, while in case of chitosan microspheres, a slight decrease in drug content was observed after 2 years of storage at the same conditions. The results obtained within this investigation revealed higher stability of melatonin-loaded poloxamer/chitosan microspheres in relation to chitosan microspheres with the same drug entrapped.

• Keywords: kitozan; melatonin; poloksamer; mikrosfere; sušenje raspršivanjem; ispitivanje stabilnosti
• Keywords (english): chitosan; melatonin; poloxamer; microspheres; spray-drying; stability studies
• Language: croatian
• URN:NBN: urn:nbn:hr:163:651818
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-01-25 10:01:54