Principima zelene kemije do lijeka poboljšanih svojstava

master's thesis

• Title (english): By the principles of green chemistry to a drug with improved properties
• Author: Valentina Keleković
• Mentor: Krunoslav Žižek (mentor)
• Committee member: Krunoslav Žižek (predsjednik povjerenstva)
• Committee member: Irena Škorić (član povjerenstva)
• Committee member: Katarina Mužina (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2023-07-14, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering

Abstract

Jedan od izazova s kojim se danas susreće farmaceutska industrija je slaba topljivost većine novo-sintetiziranih djelatnih tvari u intestinalnim fluidima, što rezultira i niskom bioraspoloživosti i slabim farmakoterapijskim učinkom lijeka. U ovom istraživanju, nastoji se poboljšati otapanje modelne djelatne tvari X pristupom koji poštuje načela zelene kemije. Mehanokemijski su pripravljene disperzije čvrste djelatne tvari X u matrici hidrofilnog polimera poli(vinil-pirolidona) (PVP) u planetarnom kugličnom mlinu. Dobivene disperzije karakterizirane su diferencijalnom pretražnom kalorimetrijom, rendgenskom difrakcijskom analizom praha i infracrvenom spektroskopijom. Pripravljene su tablete čiste netretirane djelatne tvari, mehanokemijski tretirane djelatne tvari, te tablete s čvrstim disperzijama i fizikalne mješavine djelatne tvari i polimera. U pripravi tableta promjera 8 mm korištene su pomoćne tvari poli(etilen-glikol), natrijeva kroskarmeloza, i manitol te postupak granuliranja taljenjem u fluidiziranom sloju. Karakterizacija tableta uključivala je ispitivanje ujednačenosti masa te testiranje njihove tvrdoće i raspadljivosti. Testovi otapanja i profili oslobađanja ukazuju da mehanokemijski tretman pogoduje većoj količini oslobođene djelatne tvari.
Brže oslobađanje djelatne tvari pokazuju tablete bez polimernog nosača. Tablete koje sadrže polimer poli(vinil-pirolidon) pokazuju sporije, ali kontinuirano oslobađanje djelatne tvari. Mehanokemijski pripravljene čvrste disperzije (SD) pokazuju kontinuirano oslobođanje veće količine djelatne tvari u odnosu na one koje sadrže čistu netretiranu djelatnu tvar X.
Testirana je primjenjivost modela u opisu profila oslobađanja djelatne tvari X.

Abstract (english)

One of the challenges faced by the pharmaceutical industry is the low intestinal solubility of most newly synthesised drugs, resulting in low bioavailability and poor pharmacotherapeutic efficacy of the drug. In this research, an attempt is made to improve the dissolution of drug X through an approach that follows the principles of green chemistry. Dispersions of solid drug X in a matrix of hydrophilic polymer, poly(vinyl pyrrolidone) (PVP) were prepared mechanochemically in a planetary ball mill The prepared solid dispersions were characterized by differential scanning calorimetry, X-ray powder diffraction and infrared spectroscopy. Tablets were prepared with pure untreated drug, with mechanochemically treated drug, and with solid dispersions and physical mixtures of drug and polymer. Excipients like polyethylene glycol, croscarmellose sodium, mannitol, and fluidized bed melt granulation were used to prepare tablets with a diameter of 8 mm. Characterization of the tablets included studying the mass uniformity, and testing its hardness and disintegration. Dissolution tests and release profiles indicate that mechanochemical treatment favors greater amount of drug released. Tablets without polymeric carrier show faster drug release. Tablets that contain polymer poly(vinyl pyrrolidone) show slower and continuous drug release. Mechanochemically prepared solid dispersions (SD) indicate continuous release of higher amount of drug in comparision to those containing pure untreated drug X.
The applicability of mathematical models was tested to describe release profiles of drug X.

• Keywords: zelena kemija; poboljšanje otapanje lijeka; djelatna tvar X; čvrsta disperzija; mehanokemijska aktivacija; tableta; oslobađanje djelatne tvari
• Keywords (english): green chemistry; drug dissolution improvement; drug X; solid dispersion; mechanochemical activation; tablet; drug release
• Language: croatian
• URN:NBN: urn:nbn:hr:149:724520
• Study programme: Title: Chemical Engineering - Graduate study; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka kemijskog inženjerstva (magistar/magistra inženjer/inženjerka kemijskog inženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2023-07-14
• Created on: 2023-07-27 13:08:09