Literaturni pregled in analiza trdnih disperzij slabo vodotopnih zdravilnih učinkovin, izdelanih z iztiskanjem talin

Šenica, Leja (author), German Ilić, Ilija (mentor), Jakasanovski, Ognen (comentor)

Na trgu je vedno več zdravilnih učinkovin, ki so težko vodotopne in imajo posledično slabšo absorpcijo in biološko uporabnost. Eden izmed največjih izzivov farmacevtske industrije je povečanje biološke uporabnosti takšnih učinkovin. Izdelava trdnih disperzij z iztiskanjem talin kot napredna in kontinuirana tehnologija tako postaja vedno bolj aktualna strategija za povečanje hitrosti raztapljanja učinkovine. Namen magistrske naloge je bil literaturni pregled in analiza znanstvenih člankov na temo izdelave trdnih disperzij z iztiskanjem talin, katerih namen je bil povečati hitrost raztapljanja težko vodotopnih učinkovin. S pomočjo dveh podatkovnih baz smo pridobili 53 člankov, ki so ustrezali našim kriterijem. Po pregledu člankov smo ugotovili, da so raziskovalci večinoma uporabili učinkovine iz terapevtske skupine za bolezni srca in ožilja (32 %), ki predstavljajo eno najpogosteje predpisanih skupin zdravil, ki se največkrat uporabljajo v vsakdanjem življenju. Za izdelavo trdnih disperzij so uporabili različne nosilce. Najpogosteje uporabljeni so bili hidrofilni polimeri, kot sta KollidonVA64 ter Soluplus, ki se pojavita v 26 % in 22 % formulacijah. Opazili pa smo tudi uporabo polimerov, ki se običajno uporabljajo za druge namene, kot so npr. gastrorezistentni polimeri ali surfaktanti. Zanimalo nas je tudi, kako uspešni so bili raziskovalci pri izboljšanju hitrosti raztapljanja trdnih disperzij v primerjavi s čisto učinkovino. Zelo malo raziskav pa je nastalo trdno disperzijo nadalje obdelalo v končno farmacevtsko obliko, saj so se raziskovalci za izdelavo končne farmacevtske oblike odločili le pri 36 % formulacijah. Kljub večanju števila člankov pa nismo našli članka, ki bi spremljal vse vidike, ki so pomembni pri razvoju trdnih disperzij z iztiskanjem talin (formulacija trdnih disperzij, procesni pogoji za izdelavo, nadaljnja obdelava, končna farmacevtska oblika).

• Language: Slovenian
• Keywords: iztiskanje talin, literaturni pregled, polimer, povečanje hitrosti raztapljanja, trdne disperzije
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2022
• PID: 20.500.12556/RUL-141138
• Publication date in RUL: 23.09.2022

Secondary language

• Language: English
• Title: Literature review and analysis on solid dispersions of poorly water-soluble drugs produced with hot-melt extrusion

Abstract

The number of drug substances with poor aqueous solubility and consequently poor absorption and bioavailability is increasing on the market. One of the biggest challenges for the pharmaceutical industry is increasing the bioavailability of such drug substances. The production of solid dispersions by hot-melt extrusion as an advanced and continuous technique is becoming an increasingly relevant strategy for the enhancement of solubility of poorly soluble drugs. The purpose of this Master's Thesis was to prepare a literature review and analysis of scientific articles which involve preparation of solid dispersions by hot-melt extrusion with aim of enhancing the solubility of poorly water-soluble drug substances. With the use of two databases, we obtained 53 articles that met our criteria. After reviewing them we found out that researchers mostly used drugs from the therapeutic group of cardiovascular diseases (32 %), which are one of the most commonly prescribed drugs. Various carries have been used to produce solid dispersions. Hydrophilic polymers such as KollidonVA64 (26 %) and Soluplus (22 %) were most commonly used. We also observed the use of polymers of polymers (gastroresistant polymers and surfactants) that are commonly used for other purposes. We were also interested in how successful the researchers were in improving the dissolution of solid dispersion compared to pure drug. Only a few research articles included downstream processing of the obtained solid dispersions into final dosage form. Only 36% of researchers decided to make the final dosage form. Despite the increase in the number of articles, we did not find the article that would cover all aspects that are important in the development of solid dispersion by hot-melt extrusion (solid dispersion formulation, process conditions for production, downstreaming, final dosage form).

• Keywords: hot-melt extrusion, improved solubility, literature review, polymer, solid dispersions