Literaturni pregled in analiza trdnih disperzij slabo vodotopnih zdravilnih učinkovin, izdelanih s sušenjem z razprševanjem

Bernhard, Ana Maja (author), German Ilić, Ilija (mentor)

V zadnjih letih prihaja na trg vedno več zdravilnih učinkovin s slabo vodotopnostjo in posledično slabo biološko uporabnostjo pri peroralni aplikaciji. Eden izmed načinov povečevanja topnosti in hitrosti raztapljanja zdravilnih učinkovin je izdelava trdnih disperzij s sušenjem z razprševanjem z uporabo različnih topil in nosilcev. Namen magistrske naloge je bil literaturni pregled raziskav, v katerih so raziskovalci z namenom povečevanja topnosti in hitrosti raztapljanja slabo vodotopnih zdravilnih učinkovin izdelali trdne disperzije z metodo sušenja z razprševanjem z uporabo različnih nosilcev in topil. S sistematičnim literaturnim pregledom smo iz dveh velikih podatkovnih baz pridobili 60 raziskav, ki so ustrezale namenu našega dela. Ugotovili smo, da so raziskovalci v svoje raziskave vključili veliko različnih zdravilnih učinkovin, ki sodijo v različne terapevtske skupine. Največ zdravilnih učinkovin je sodilo v skupino zdravil za bolezni srca in ožilja, ki se tudi v vsakdanjem življenju pogosto uporabljajo. Da so dosegli ustrezno raztapljanje zdravilne učinkovine in nosilca, so uporabili različna topila, največkrat organska. Trdne disperzije so izdelali z uporabo različnih nosilcev, med katerimi so najpogosteje uporabili hidrofilne polimerne nosilce, med njimi največkrat PVP in HPMC, med tem ko so bili mezoporozni nosilci uporabljeni najmanjkrat, kar nas je glede na njihove dobre lastnosti nekoliko presenetilo. V raziskavah so izdelane trdne disperzije tudi vrednotili. Velikost delcev je sicer vrednotilo zelo malo raziskav, so pa v večini teh izdelali manjše delce kot so bili delci uporabljene zdravilne učinkovine. V večini raziskav so dosegli tudi popolno amorfizacijo zdravilne učinkovine v trdni disperziji, ki je v večini raziskav tudi ostala stabilna skozi določeno časovno obdobje pri uporabljenih pogojih testiranja. Izkoristki procesa so bili slabi, so pa raziskovalci dosegli visoke deleže vgrajene zdravilne učinkovine v trdno disperzijo. Skoraj v vseh raziskavah so z izdelavo trdnih disperzij slabo vodotopnih zdravilnih učinkovin dosegli izboljšanje hitrosti raztapljanja v primerjavi s čisto obliko zdravilne učinkovine ali fizikalno zmesjo. Zelo malo raziskav se je ukvarjalo z vgradnjo trdne disperzije v končno farmacevtsko obliko. Raziskav z izdelavo trdnih disperzij, izdelanih s sušenjem z razprševanjem je sicer veliko, vendar med njimi zelo malo z mezoporoznimi nosilci, zato bi bilo v prihodnosti smiselno načrtovati več raziskav z njihovo uporabo. Čeprav so trdne disperzije zelo proučevano področje, je število formulacij na trgu še vedno majhno, zato bi bilo v prihodnje smiselno raziskovati tudi v tej smeri.

• Language: Slovenian
• Keywords: trdne disperzije, sušenje z razprševanjem, hidrofilni polimeri, mezoporozni nosilci, literaturni pregled, izboljšanje topnosti in hitrosti raztapljanja
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2021
• PID: 20.500.12556/RUL-133203
• Publication date in RUL: 17.11.2021

Secondary language

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

Abstract

In recent years, more and more active ingredients have come onto the market that are poorly soluble in water and consequently have low oral bioavailability. One way to increase the solubility and dissolution rate of active ingredients is to prepare solid dispersions by spray drying using different solvents and carriers. The aim of this Master Thesis was to review the literature on studies in which researchers have prepared solid dispersions by spray drying using different carriers and solvents to increase the solubility and dissolution rate of poorly water soluble active pharmaceutical ingredients. Our systematic literature search identified 60 studies from two major databases that were relevant for the purposes of our work. We found that researchers included many different active ingredients in their studies, belonging to different therapeutic groups. Most of the agents belonged to the group of cardiovascular drugs, which are also widely used in daily life. Different solvents, mostly organic, were used to achieve proper dissolution of the drug and carrier. Solid dispersions were prepared using a variety of carriers, with hydrophilic polymeric carriers being the most commonly used, especially PVP and HPMC. Mesoporous carriers were the least used, which was somewhat surprising given their good properties. The surveys also evaluated the solid dispersions prepared. Although very few studies evaluated particle size, most of them produced particles smaller than those of the active ingredient used. Most of the studies also achieved complete amorphization of the active ingredient in the solid dispersion, which remained stable for a period of time under the test conditions used. The process yields were low, but the researchers achieved high percentages of the active ingredient incorporated into the solid dispersion. In almost all the studies, preparation of solid dispersions of poorly water soluble active pharmaceutical ingredients resulted in improvement in dissolution rate as compared to pure form of active pharmaceutical ingredient or physical mixture. Very few articles dealt with the incorporation of solid dispersions into the final dosage form. While there has been a lot of research on the preparation of spray-dried solid dispersions, very little of it has been done with mesoporous carriers, and it would be worthwhile to do more research with them in the future. Although solid dispersions are well researched, the number of formulations on the market is still small, so it would be useful to research them further in the future.

• Keywords: solid dispersions, spray-drying, hydrophilic polymers, mesoporous carriers, literature review, solubility and dissolution rate improvement