Mikrosfere temeljene na pektinu i hipromelozi za nazalnu primjenu natrijevog deksametazon fosfata

master's thesis

• Title (english): Pectin and hypromellose based microspheres for nasal delivery of dexamethasone sodium phosphate
• Author: Matea Pačarić
• 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: 2020-02-14, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Nazalna primjena kortikosteroida indicirana je u liječenju akutnih i kroničnih upalnih bolesti sluznice nosa. Nedostatak registriranih pripravaka u obliku kapi ili spreja za nos je kratko zadržavanje na mjestu primjene. Zbog toga se razvijaju novi terapijski sustavi koji osiguravaju dulji kontakt s nosnom sluznicom i kontrolirano oslobađanje lijeka, a jedan od takvih sustava su polimerne mikrosfere s uklopljenim lijekom za nazalnu primjenu. U ovom diplomskom radu metodom sušenja raspršivanjem pripremljene su mikrosfere temeljene na pektinu i hipromelozi s uklopljenim natrijevim deksametazon fosfatom (NDP). Cilj rada bio je ispitati utjecaj masenog omjera pektina i hipromeloze u polimernom matriksu na svojstva dobivenih mikrosfera koja su važna kod nazalne primjene praškastih sustava. Mikrosfere s uklopljenim NDP-om masenog omjera pektina i hipromeloze od 1:0, 1:1, 1:2 i 2:1 uspješno su pripremljene sušenjem raspršivanjem otopine NDP-a koncentracije 0,01% (m/V) i otopina polimera ukupne koncentracije 0,5% (m/V). Iskorištenje procesa sušenja raspršivanjem kretalo se od 46 do 64%. Dobivene mikrosfere karakterizirane su srednjim promjerom od 3,13 ± 0,46 i 3,82 ± 0,32 μm. Kod svih uzoraka mikrosfera uočena je slična raspodjela veličina čestica pri čemu oko 80% ima promjer manji od 5 μm. Sadržaj NDP-a iznosio je između 1,83 i 2,24%. U procesu bubrenja uočeno je da mikrosfere s većim sadržajem pektina u odnosu na hipromelozu pokazuju veći stupanj bubrenja u pročišćenoj vodi, dok uklopljeni lijek nema značajan utjecaj na svojstva bubrenja. Svi uzorci mikrosfera apsorbirali su značajno manji volumen SNF-a po jediničnoj masi u usporedbi s pročišćenom vodom. Utvrđeno je brzo inicijalno oslobađanje lijeka tijekom prvih 60 min (77,0 ± 2,6 - 89,4 ± 5,9 %), nakon čega slijedi sporija faza oslobađanja. Nije uočena značajna razlika u brzini oslobađanja lijeka između različitih uzoraka mikrosfera.

Abstract (english)

Nasal administration of corticosteroids is indicated in the treatment of acute and chronic inflammatory diseases of nasal mucosa. A disadvantage of registered drugs in the form of drops or nasal spray is short retention time on the application site. Therefore, new drug delivery systems with prolonged contact with nasal mucosa and controlled release of the drug at the site of administration are being developed, such as polymeric drug loaded microspheres.
In this diploma thesis, sodium dexamethasone phosphate (SDP) loaded microspheres based on pectin and hypromellose for nasal administration were prepared by spray-drying method. The aim of this study was to investigate the influence of pectin to hypromellose weight ratio in the polymeric matrix on the obtained microspheres' properties which are important for nasal powder systems. SDP loaded microspheres with pectin to hypromellose weight ratio of 1:0, 1:1, 1:2 and 2:1 were successfully prepared by spray-drying of SDP solution at concentration of 0.01% (w/v) and polymer(s) solution at total concentration of 0.5% (w/v). Process yield ranged between 46 and 64%. Obtained microspheres are characterized by mean diameter from 3.13 ± 0.46 to 3.82 ± 0.32 μm. A similar particle sizes distribution is observed in all microspheres samples with about 80% of particles having a diameter smaller than 5 μm. Microspheres were characterized by drug loading from 1.83 to 2.24%. In the swelling process, microspheres with higher pectin content in comparison to hypromellose showed a higher swelling degree, while the incorporated drug had no significant effect on the swelling properties. All microsphere samples absorbed significantly less SNF volume per mass unit in comparison to the purified water. Rapid initial drug release during the first 60 min (77.0 ± 2.6 - 89.4 ± 5.9%) was observed, followed by a slower release phase. No significant difference was observed in the in vitro release rate between different microsphere samples.

• Keywords: natrijev deksametazon fosfat; pektin; hipromeloza; sušenje raspršivanjem; mikrosfere; nazalna primjena lijeka
• Keywords (english): sodium dexamethasone phosphate; pectin; hypromellose; spray drying; microspheres; nasal drug delivery
• Language: croatian
• URN:NBN: urn:nbn:hr:163:525452
• 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: 2021-04-30 15:00:18