Uloga čvrstih disperzija u povećanju topljivosti i brzine oslobađanja djelatne tvari

master's thesis

• Title (english): The role of solid dispersions for improving solubility and release rate of drug
• Author: Katarina Sokač
• Mentor: Krunoslav Žižek (mentor)
• Committee member: Krunoslav Žižek (predsjednik povjerenstva)
• Committee member: Vesna Tomašić (član povjerenstva)
• Committee member: Irena Škorić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2021-09-17, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering

Abstract

Lurasidon-hidroklorid je antipsihotik novije generacije koji pokazuje svojstvo izrazito male topljivosti u vodenom mediju. Navedeno rezultira usporenim farmakološkim djelovanjem i nedovoljnom efikasnošću pri liječenju psihičkih bolesti. S ciljem povećanja njegove topljivosti pripravljene su čvrste disperzije djelatne tvari u matrici hidrofilnog polimera, poli(etilen-glikola), metodom isparavanja otapala. Dobivene čvrste disperzije karakterizirane su rendgenskom difrakcijom na praškastom uzorku, infracrvenom spektroskopijom s Fourierovom transformacijom te diferencijalnom pretražnom kalorimetrijom. Pripravljene čvrste disperzije korištene su u pripravi raspadljivih tableta za usta. Kao pomoćne tvari korišteni su manitol, mikrokristalna celuloza, natrijeva kroskarmeloza, poli(etilen-glikol) i magnezijev stearat. Karakterizacija raspadljivih tableta podrazumijevala je ispitivanje njihove tvrdoće, raspadljivosti te sadržaja lurasidon-hidroklorida. In vitro ispitivanjima određena je topljivost djelatne tvari te profili njezina oslobađanja iz raspadljivih tableta. Dobivene tablete posjeduju zadovoljavajuća svojstva jer imaju tvrdoću i raspadljivost u skladu s preporukama Europske farmakopeje te se mogu klasificirati kao raspadljive tablete za oralnu primjenu. Profili oslobađanja u laboratorijskom okruženju i prisutnosti McIlvaineovog pufera (pH = 3,8) ukazuju na značajno poboljšanje topljivosti i brzine oslobađanja djelatne tvari iz raspadljivih tableta pripravljenih iz čvrstih disperzija u odnosu na one koje sadrže čisti LRS HCl i fizikalnu mješavinu djelatne tvari i polimera. Testirana je primjenjivost matematičkih modela u opisu profila oslobađanja lurasidon-hidroklorida.

Abstract (english)

Lurasidone hydrochloride is an antipsychotic of a newer generation that shows the property of extremely low solubility in an aqueous medium. This results in a delayed pharmacological effect and insufficient efficacy in the treatment of mental illnesses. In order to increase its solubility, solid dispersions of drug were prepared in a matrix of hydrophilic polymer, poly(ethylene glycol), by the solvent evaporation method. The obtained solid dispersions were characterized by X-ray powder diffraction, Fourier-transform infrared spectroscopy and differential scanning calorimetry. Prepared solid dispersions were used in the preparation of orally disintegrating tablets. Mannitol, microcrystalline cellulose, croscarmellose sodium, poly(ethylene glycol) and magnesium stearate were used as excipients. Characterization of disintegrating tablets involved testing their hardness, disintegration and the content of lurasidone hydrochloride. Drug solubility and its release profiles from disintegrating tablets were detected as well using in vitro dissolution tests. The obtained tablets have satisfactory properties because they have hardness and disintegration in accordance with the recommendations of the European Pharmacopoeia and can be classified as disintegrating tablets for oral administration. In vitro release profiles in the presence of McIlvaine buffer (pH = 3.8) indicate a significant improvement in the solubility and release rate of drug from disintegrating tablets prepared from solid dispersions in comparison to those containing pure LRS HCl and physical mixtures of drug and polymer. The applicability of mathematical models was tested to describe release profiles for lurasidone hydrochloride.

• Keywords: lurasidon-hidroklorid; poboljšanje topljivosti lijeka; čvrsta disperzija; metoda isparavanja otapala; raspadljiva tableta za usta; oslobađanje djelatne tvari
• Keywords (english): lurasidone hydrochloride; drug solubility improvement; solid dispersion; solvent evaporation method; orally disintegrating tablet; drug release
• Language: croatian
• URN:NBN: urn:nbn:hr:149:742761
• Study programme: Title: Materials Science and 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: 2021-09-17
• Created on: 2023-04-14 09:59:10