Ispitivanje utjecaja laktoze i manitola na svojstva praškastog sustava s natrijevim deksamatazon fosfatom za nazalnu primjenu

master's thesis

• Title (english): Investigation of the effect of lactose and mannitol on nasal powder delivery system of sodium dexamethasone phosphate
• Author: Sara Blažon
• Mentor: Anita Hafner (mentor)
• Committee member: Anita Hafner (predsjednik povjerenstva)
• Committee member: Ivan Pepić (član povjerenstva)
• Committee member: Maja Ortner Hadžiabdić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical technology); Zagreb
• Defense date and country: 2021-06-29, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Nazalna primjena kortikosteroida primaran je način dostave lijeka kod bolesti nosa i sinusa jer omogućava brži početak djelovanja te smanjenu sistemsku apsorpciju. Nedostaci konvencionalnih tekućih oblika doveli su do razvoja praškastih sustava za nazalnu primjenu koji omogućuju veću koncentraciju djelatne tvari na mjestu primjene, bolju stabilnost formulacije te produljeno zadržavanje na mjestu primjene. Jedan od takvih sustava su polimerne mikrosfere s uklopljenom djelatnom tvari.
U ovom su radu mikrosfere pripravljene sušenjem raspršivanjem otopine natrijevog deksametazon fosfata, pektina i hipromeloze u masenom omjeru 1:1:1. Iskorištenje procesa iznosilo je 65,7 ± 8,7 %, a uspješnost uklapanja natrijevog deksametazon fosfata u mikrosfere 94,4 ± 0,4 %. Praškasti sustavi mikrosfera i inertnog nosača (α-laktoza monohidrat ili manitol) pripravljeni su miješanjem u omjerima 1:1, 1:2, 1:4, 1:7 te 1:9 (m/m) uz zadovoljene kriterije homogenosti. Uočeno je poboljšanje reoloških svojstava praškastih sustava s inertnim nosačem u odnosu na same mikrosfere. Praškasti sustavi s ispitivanim inertnim nosačima usporedivih su reoloških svojstava. Svojstva bubrenja mikrosfera u umjetnom nazalnom fluidu bila su umjerenija u odnosu na pročišćenu vodu. Dodatak inertnog nosača povećao je volumen apsorbiranog medija u donorskom odjeljku po miligramu mikrosfera, proporcionalno udjelu nosača. Provedenom karakterizacijom praškastih sustava utvrđena je prikladnost laktoze monohidrata i manitola kao nosača mikrosfera za nazalnu primjenu. Sustavi masenog omjera mikrosfera i inertnog nosača od 1:9 pokazali su se najprikladnijima za dodatna in vitro te in vivo ispitivanja.

Abstract (english)

Nasal administration of corticosteroids is the primary method of drug delivery for sinonasal disease treatment since it enables a rapid onset of action and reduced systematic absorption. Disadvantages of conventional liquid formulations led to the development of powder formulations that assure higher local drug concentration, increased stability of the formulation, as well as prolonged drug retention at the nasal mucosa. One type of those systems encompasses polymer-based, drug-loaded microspheres.
In this study microspheres were prepared by spray-drying of solution containing sodium dexamethasone phosphate, pectin and hypromellose in 1:1:1 (w/w/w) ratio. Process yield was 65.7 ± 8.7 %, whilst sodium dexamethasone phosphate entrapment efficiency was 94.4 ± 0.4 %. Powder systems containing microspheres and inert carrier (α-lactose monohydrate or mannitol) were prepared by mixing components in 1:1, 1:2, 1:4, 1:7 and 1:9 (w/w) ratios, assuring the homogeneity of the mixtures. Powders containing inert carrier demonstrated improvement of reological properties in comparison with microspheres alone. Powder systems with α-lactose monohydrate had comparable rheological properties to powder systems with mannitol. Swelling properties of the microspheres in simulated nasal fluid were moderate compared to purified water. Addition of an inert carrier increased volume of absorbed medium per milligram of microspheres in the donor compartment, proportionally to the mass fraction of inert carrier. Characterisation of powder systems demonstrated suitability of lactose monohydrate and mannitol as carriers of microspheres for nasal delivery. Systems containing microsperes and inert carrier in weight ratio of 1:9 have proven to be the most suitable for additional in vitro and in vivo tests.

• Keywords: nazalna primjena; natrijev deksametazon fosfat; mikrosfere; pektin; hipromeloza; inertni nosači
• Keywords (english): nasal delivery; sodium dexamethasone phosphate; microspheres; pectin; hypromellose; inert carrier
• Language: croatian
• URN:NBN: urn:nbn:hr:163:208315
• 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: 2022-02-02 12:13:37