Proučevanje lastnosti trdnih disperzij fenofibrata z mezoporoznim SiO2, izdelanih s pomočjo različnih organskih topil

Sluga, Selestina (author), Planinšek, Odon (mentor)

Nekatere farmacevtske učinkovine imajo kljub želenim terapevtskim učinkom lastnosti, ki otežujejo njihovo uporabo in proizvodnjo farmacevtskih oblik. Mednje sodi učinkovina fenofibrat, ki izkazuje slabo topnost. Eden izmed pristopov za izboljšanje topnosti je izdelava trdnih disperzij. Izdelujemo jih iz učinkovine in pomožnih snovi, pri čemer pogosto uporabljamo mezoporozne materiale, katerim specifična struktura in velika površina omogoča nalaganje zdravilne učinkovine v pore nosilca. Učinkovitost izdelanega dostavnega sistema lahko preverjamo s farmakopejskim testom sproščanja, ki daje podatek o deležu učinkovine, ki se je sprostila in raztopila v mediju v določeni časovni točki. Izdelali smo formulacije, z učinkovino in mezoporozno pomožno snovjo Syloid® 244 FP, v petih različnih koncentracijah, v korakih po 10%. Želeli smo ugotoviti kako delež učinkovine v disperziji vpliva na sproščanje v ustreznem diskriminatornem mediju. Trdne disperzije smo izdelovali pri različnih pogojih (organsko topilo, temperatura, tlak), pri čemer smo želeli, prav tako ugotoviti, kako ti vplivajo na delež sproščene učinkovine. S pomočjo testa sproščanja, ki smo ga izvedli pri pH=1,2, smo izbrali najbolj optimalno trdno disperzijo in jo uporabili za izdelavo tablet. Izdelanim tabletam smo izmerili trdnost, razpadni čas in izvedli test sproščanja. Ugotovili smo, da izdelava trdnih disperzij bistveno izboljša topnost učinkovine v primerjavi s fizikalnimi zmesmi ali s čisto učinkovino. Rezultati so povezani z amorfnostjo učinkovine v trdnih disperzijah, kar smo dokazali z odsotnostjo tališča pri segrevanju vzorcev in veliko specifično površino s katere se učinkovina raztaplja. Ugotovili smo, da je učinkovitost izboljšanja raztapljanja odvisna tudi od uporabe organskega topila, saj je učinkovina bolje topna v acetonu v primerjavi z izopropanolom. Posledično je bila večja učinkovitost vgrajevanja učinkovine v pore Syloida in večji delež raztopljene učinkovine v primeru uporabe acetona za izdelavo trdne disperzije. Na koncu smo izdelali orodisperzibilne tablete z vsebnostjo učinkovine 20%, ki so razpadle v manj kot 30 sekundah in se je iz njih sprostilo 90% učinkovine v 120 minutah.

• Language: Slovenian
• Keywords: slabo topne učinkovine, fenofibrat, trdne disperzije, test sproščanja
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2023
• PID: 20.500.12556/RUL-145881
• Publication date in RUL: 17.05.2023

Secondary language

• Language: English
• Title: Studying the properties of fenofibrate solid dispersions with mesoporous SiO2 produced by using different organic solvents

Abstract

Some active pharmaceutical ingredients, despite their desired therapeutic effects, have properties that make their use and the production of pharmaceutical dosage forms difficult. These include the active substance fenofibrate, which has poor solubility. One approach to improve solubility is to produce solid dispersions. These are made from the active substance and excipients, often using mesoporous materials whose specific structure and large surface area allow the active substance to be loaded into the pores. The efficacy of the constructed delivery system can be verified by a pharmacopoeial release test, which gives an indication of the proportion of the active substance that has been released and dissolved in the medium. We have produced formulations with the active substance and the mesoporous excipient Syloid®244 FP in five different concentrations, in 10% increments. We wanted to determine how the proportion of the active ingredient in the dispersion affects the release in a suitable discriminatory medium. Solid dispersions were made under different conditions (organic solvent, temperature, pressure) and we also wanted to find out how these affect the proportion of active substance released. The best solid dispersion was selected and used for the production of tablets by means of a release test carried out at pH=1.2. The tablets were measured for strength, disintegration time and release test. We found that the production of solid dispersions significantly improved the solubility of the active substance compared to physical mixtures or to the pure active substance. The results are related to the amorphous nature of the active substance in the solid dispersions, which was demonstrated by the absence of melting point when the samples were heated and the large specific surface area from which the active substance dissolves. We found that the efficiency of the dissolution enhancement also depends on the use of an organic solvent, as the active substance is more soluble in acetone compared to isopropanol. As a result, there was a higher efficiency of incorporation of the active substance into the pores of the Syloid and a higher percentage of the active substance dissolved in the case of using acetone to produce a solid dispersion. Finally, orodispersible tablets with an active ingredient content of 20% were produced, which disintegrated in less than 30 seconds and released 90% of the active ingredient in 120 minutes.

• Keywords: poorly soluble active ingredients, fenofibrate, solid dispersions, release