Primerjava lastnosti trdnih disperzij karvedilola s tremi mezoporoznimi nosilci, izdelanimi s sušenjem z razprševanjem

Orlač, Anja (author), German Ilić, Ilija (mentor)

Zdravilne učinkovine, ki jih v zadnjih letih razvijajo ali pridejo na trg, po večini izkazujejo slabo vodotopnost in posledično prenizko biološko uporabnost za doseganje zadovoljivih terapevtskih učinkov pri peroralni aplikaciji zdravil. S ciljem povečanja biološke uporabnosti slabo vodotopne zdravilne učinkovine, smo z metodo sušenja z razprševanjem, izdelali trdne disperzije. Namen je bil vgraditi karvedilol v pore mezoporoznih nosilcev, ob uporabi hlapnega organskega topila, in izdelati amorfno obliko zdravilne učinkovine z izboljšano vodotopnostjo. Uporabili smo tri mezoporozne nosilce (Syloid 244 FP, Aeroperl 300 in Syloid XDP 3150) in zdravilno učinkovino karvedilol, ki smo ju pred procesom sušenja z razprševanjem dispergirali v 100 ml acetona. Spreminjali smo razmerje med učinkovino in nosilcem (1 : 5, 1 : 3, 1 : 2, 1 : 1 in 1,5 : 1) ter na trdnih disperzijah opravili različne analize. Z diferenčno dinamično kalorimetrijo smo vrednotili kristaliničnost oz. amorfnost učinkovine, z UV-VIS spektroskopijo njeno vsebnost in z lasersko difraktometrijo velikost delcev. Določili smo tudi prave gostote, pretočne lastnosti ter izvedli poskuse sproščanja. V vseh primerih smo dosegli popolno amorfnost karvedilola, a rezultati so pokazali, da je bilo največje izboljšanje hitrosti raztapljanja doseženo ob uporabi Syloida 244 FP, kar je koreliralo z majhno velikostjo delcev nosilca. Izdelava trdnih disperzij ni bistveno spremenila velikosti delcev, saj so trdne disperzije podobne velikosti kot uporabljen nosilec. Slaba pretočnost Syloida je pripomogla k slabšim pretočnim lastnostim trdnih disperzij izdelanih s tem nosilcem. Rezultati sproščanja so pokazali, da se zdravilna učinkovina iz trdnih disperzij sprošča 2–3x hitreje v primerjavi s fizikalno zmesjo in samo zdravilno učinkovino. Na podlagi vseh analiz smo zaključili, da je uspešnost vgradnje učinkovine v pore močno odvisna od velikosti delcev nosilca. Z manjšanjem velikosti nosilca je proces uspešnejši, boljše rezultate sproščanja pa dajejo razmerja z manjšim deležem učinkovine. Z izdelavo trdne disperzije v razmerju karvedilol : Syloid 244 FP = 1 : 2, ki je dala najboljše rezultate, smo pokazali, da trdne disperzije kažejo velik potencial za izboljšanje topnosti in hitrosti raztapljanja slabo vodotopnih učinkovin. Glede na dosedanje raziskave lahko rečemo, da trdne disperzije v prihodnosti še veliko obetajo.

• Language: Slovenian
• Keywords: trdna disperzija, amorf, sušenje z razprševanjem, karvedilol, mezoporozni nosilec
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2022
• PID: 20.500.12556/RUL-143402
• Publication date in RUL: 20.12.2022

Secondary language

• Language: English
• Title: Property comparison of carvedilol solid dispersions containing three mesoporous carriers, prepared using spray drying

Abstract

The active substances developed or marketed in recent years generally exhibit poor water solubility and consequently too low bioavailability to achieve satisfactory therapeutic effects when administered orally. In order to increase the bioavailability of the poorly water-soluble active substance, solid dispersions were produced by spray-drying. The aim was to incorporate carvedilol into the pores of mesoporous carriers, using a volatile organic solvent, and to produce an amorphous form of the active substance with improved water solubility. Three mesoporous carriers (Syloid 244 FP, Aeroperl 300 and Syloid XDP 3150) and the active substance carvedilol were used and dispersed in 100 ml of acetone prior to the spray-drying process. We varied the ratio of active substance to carrier (1 : 5, 1 : 3, 1 : 2, 1 : 1 and 1. 5 : 1) and performed various analyses on the produced solid dispersions. The crystalline/amorphous nature of the active substance was evaluated by differential dynamic scanning calorimetry, its content by UV-VIS spectroscopy and particle size by laser diffractometry. We have also determined the true densities, flow properties and conducted dissolution experiments. In all cases, carvedilol was completely amorphous, but the results showed that the greatest dissolution improvement was achieved using Syloid 244 FP, which correlated with the small particle size of the carrier. The production of solid dispersions did not significantly change the particle size, as the solid dispersions are of a similar size to the used carrier. The poor flowability of Syloid has contributed to the poorer flow properties of solid dispersions produced with this carrier. The dissolution results showed that the active substance was released 2–3 times faster from solid dispersions compared to the physical mixture and the active substance alone. Based on all the analyses, we conclude that the success of the incorporation of the active substance into the pores is strongly dependent on the particle size of the carrier. Reducing the carrier size makes the process more efficient, while ratios with a lower proportion of the active substance give faster release. By producing a solid dispersion with the ratio of carvedilol : Syloid 244 FP = 1 : 2, which gave the best results, we have shown that solid dispersions show great potential for improving the solubility and dissolution rate of poorly water-soluble active substances. Based on the research so far, solid dispersions hold great promise for the future.

• Keywords: solid dispersion, amorphous, spray – drying, carvedilol, mesoporous carrier