[diplomska naloga]
Maruša Cvek (Author), Odon Planinšek (Mentor)

Abstract

Vgrajevanje učinkovin v trdne disperzije z uporabo poroznih pomožnih snovi lahko predstavlja obetaven način za izboljšanje topnosti v vodi slabo topnih zdravilnih učinkovin. Cilj diplomske naloge je bil izdelava multiplih trdnih disperzij, kjer smo učinkovino karvedilol najprej raztopili v izbrani tekoči pomožni snovi oziroma talini, nato pa s to raztopino impregnirali porozni silicijev dioksid. Metoda, ki smo jo uporabili za izdelavo je najbolj podobna metodi granuliranja s talinami. Kot pomožne snovi smo uporabili dva polietilenglikola z različnima molekulskima masama (PEG 400, PEG 4000) neionsko površinsko aktivno snov polioksietilen (20) sorbitan monooleat (Tween 80), in porozni silicijev dioksid (Syloid 244 FP). Vse izbrane pomožne snovi razen silicijevega dioksida izkazujejo dobro topnost v vodnih medijih. Ocenili smo, da se karvedilol najbolje raztaplja v PEG 400, najmanj pa v Tween 80. Z merjenjem viskoznosti smo ugotovili, da je najbolj viskozna pomožna snov staljeni PEG 4000, sledi ji Tween 80, najmanj viskozen pa je PEG 400. Raztopine karvedilola v pomožnih snoveh imajo višjo viskoznost od čistih pomožnih snovi. Raztapljanje same učinkovine, iz raztopine učinkovine v pomožni snovi ter iz multiple trdne disperzije smo vrednotili s preizkusom raztapljanja po Ph. Eur. 7th Ed.. Lastnosti multiple trdne disperzije smo vrednotili s termično analizo (DSC) ter merjenjem specifične površine (BET), morfologijo delcev pa z vrstičnim elektronskim mikroskopom (SEM). Ugotovili smo, da se učinkovina iz trdne disperzije hitreje in bolje sprošča kot njena kristalna oblika, hkrati pa je bilo sproščanje učinkovine iz trdne disperzije primerljivo s sproščanjem iz raztopine učinkovine v pomožni snovi. S termično analizo smo ugotovili, da se učinkovina v multipli trdni disperziji ter v raztopini učinkovine v izbrani pomožni snovi nahaja v amorfni obliki in je v porah najverjetneje raztopljena v pomožni snovi S pomočjo elektronskega mikroskopa (SEM) ter merjenjem specifične površine (BET) smo potrdili, da se je raztopina karvedilola v izbrani pomožni snovi porazdelila pretežno v pore Syloida 244 FP. Glede na meritve specifične površine je najboljše rezultate dala multipla trdna disperzija s Tween 80 kot pomožno snovjo. Zaradi svoje visoke viskoznosti ter visoke temperature tališča pa PEG 4000 predstavlja pomožno snov, ki najtežje prodira v pore Syloida 244. Posledično je bilo sproščanje učinkovine iz te multiple trdne disperzije najmanj izboljšano.

Keywords

trdne disperzije;izdelava trdnih disperzij;modelna učinkovina;pomožne snovi;farmacevtska tehnologija;multiple trdne disperzije;vgrajevanje učinkovin;

Data

Language: Slovenian
Year of publishing:
Source: Ljubljana
Typology: 2.11 - Undergraduate Thesis
Organization: UL FFA - Faculty of Pharmacy
Publisher: [M. Cvek]
UDC: 66.061+66.095+661.12(043.2)
COBISS: 3396977 Link will open in a new window
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Other data

Secondary language: English
Secondary title: Formulation of multiple solid dispersions with carvedilol at elevated temperature
Secondary abstract: Formulation of solid dispersions by using porous carriers can reperesent a promissing method of solubility improvement for poorly water soluble drugs. The aim of our study was to formulate multiple solid dispersions. Hence we firstly dissolved our drug carvedilol in a selected liquid excipient or melt and then impregnated the porous silicon dioxide with this solution. The method used for this formulation is the most similar to melt agglomeration method. We used two polyethylene glycols with different molecular masses (PEG 400 and PEG 4000), nonionic surfactant polyoxyethylene (20) sorbitan monooleate (Tween 80) and porous silicon dioxide (Syloid 244 FP) as our excipients. With the exception of silicon dioxide all selected excipients show a good water-solubility. After our evaluation we conculded that carvedilol shows the best solubility in PEG 400 and the worst in Tween 80. Viscosity measures proved melted PEG 4000 to be the most viscid excipient followed by Tween 80. PEG 400 showed the lowest viscosity. Carvedilol solutions exhibit higher viscosity than excipients alone. We evaluated dissolution of the drug from the drug-excipient solution and from multiple solid dispersions with a dissolution test according to Ph. Eur. 7th Ed.. We also evaluated the properties of multiple solid dispersions by using thermal analysis (DSC) and specific surface area measurements (BET). The morphology of the particles was evaluated using the scanning electron microscope (SEM). It was evident during our study that the drug release from solid dispersion is faster and better than from its crystalline form. The drug release from solid dispersion was at the same time comparable with its release from drug-excipient solution. Our results made by using thermal analysis method show that in multiple solid dispersions and in drug-excipient solutions carvedilol is in amorphous form and that it is probably incorporated into pores as a drug-excipient solution. With the help of the electronic microscop (SEM) and specific surface area measurements (BET) we were able to confirm that the carvedilol solution in a selected excipient distributed itself mainly in the Syloid 244 FP pores. The best results regarding specific surface area measurements gave multiple solid dispersion with Tween 80 as an exscipient. PEG 4000 however classifies as an excipient which penetrates Syloid 244 FP pores most difficultly due to its high viscosity and high melting temperature. The drug release from this multiple solid dispersion was consequently least improved.
Type (COBISS): Undergraduate thesis
Thesis comment: Univ. v Ljubljani, Fakulteta za farmacijo
Pages: VII, 55 f.
ID: 12053296