Literaturni pregled trdnih disperzij težko vodotopnih zdravilnih učinkovin z različnimi komercialno dostopnimi mezoporoznimi delci silicijevega dioksida za peroralno uporabo

Baumgartner, Ana (avtor), Planinšek, Odon (mentor)

V zadnjem času se v farmacevtskem razvoju pogosto srečujemo s težko vodotopnimi zdravilnimi učinkovinami, kar lahko predstavlja velik izziv pri razvoju peroralne farmacevtske oblike. Eden izmed načinov za izboljševanje topnosti in hitrosti raztapljanja zdravilne učinkovine je izdelava trdne disperzije, pri kateri pomožno snov predstavlja mezoporozni silicijev dioksid. Namen magistrske naloge je bil eksperimentalno določiti nekatere pomembne fizikalno-kemijske lastnosti različnih komercialno dostopnih mezoporoznih delcev silicijevega dioksida, ki lahko raziskovalcem pomagajo pri izbiri ustrezne pomožne snovi za izdelavo trdne disperzije, ter nadalje narediti literaturni pregled že obstoječih raziskav, v katerih so raziskovalci te snovi že uporabljali pri izdelavi trdnih disperzij težko vodotopnih učinkovin. Šestim različnim vrstam komercialno dostopnih delcev SiO2 (Aeroperl 200, Parteck SLC 500, Syloid XDP 3050, Syloid XDP 3150, Syloid 244 FP, Syloid AL-1 FP) smo določili morfologijo in velikost delcev, specifično površino, velikost in volumen por, pretočne lastnosti in vsebnost ter afiniteto do vlage. Ugotovili smo, da se delci po omenjenih lastnostih med seboj precej razlikujejo, katera vrsta pa je za izdelavo trdne disperzije najbolj optimalna, pa je precej odvisno od ciljev raziskave in razvoja formulacije. S sistematičnim literaturnim pregledom dveh različnih podatkovnih baz smo našli 60 člankov, ki so ustrezali namenu našega dela. Ugotovili smo, da raziskovalci pri delu uporabljajo precej različne učinkovine iz številnih terapevtskih skupin, kot pomožno snov pa so najpogosteje uporabili vrste SiO2 z majhnimi delci in večjimi porami, npr. Sylysio 350 in Syloid 244 FP. Za izdelavo trdnih disperzij so uporabili več različnih metod, med katerimi prednjačijo metode z odparevanjem organskega topila. V večini raziskav so dobili popolnoma oz. večinoma amorfno učinkovino, prav tako je bila večina formulacij stabilnih pri uporabljenih pogojih testiranja. Skoraj v vseh raziskavah so z vgradnjo težko vodotopne učinkovine v trdno disperzijo dosegli izboljšanje raztapljanja; včasih zgolj hitrost raztapljanja, velikokrat pa tudi delež raztopljenega odmerka. Precej malo raziskav se je ukvarjalo tudi z izdelavo končne farmacevtske oblike ter potrjevanjem testiranj in vitro z rezultati in vivo. V končnih farmacevtskih oblikah, ki so bile po navadi tablete, je bil delež učinkovine pogosto precej nizek zaradi slabih tabletirnih lastnosti čiste trdne disperzije. Pri testiranjih in vivo so ugotavljali izboljšanje farmakokinetičnih lastnosti z vgradnjo učinkovine v trdno disperzijo. V prihodnje bi bilo verjetno smiselno načrtovati več raziskav, kjer bi bil cilj izdelava takšne formulacije, ki bi imela v končni fazi lahko tudi prostor na trgu.

• Jezik: Slovenski jezik
• Ključne besede: trdne disperzije, mezoporozni silicijev dioksid, literaturni pregled, izboljšanje topnosti in hitrosti raztapljanja
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2020
• PID: 20.500.12556/RUL-118616
• Datum objave v RUL: 28.08.2020

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Literature review of solid dispersions containing poorly water-soluble drugs and various commercially available mesoporous silica materials intended for oral use

Izvleček

Nowadays, more and more active pharmaceutical ingredients have poor water solubility, which represents an important challenge in drug discovery and development of oral dosage forms. One of the approaches to enhance water solubility and dissolution rate is to make a solid dispersion, in which a drug is incorporated into mesoporous silica material. The aims of this Master thesis was to experimentally evaluate some of the important physio-chemical characteristics of different commercially available mesoporous silica materials, which could help the researchers to decide about the most appropriate excipient to formulate a solid dispersion, and to make a literature review of already published articles, in which these excipients were used to formulate solid dispersions of poorly water-soluble drug. Six different kinds of commercially available SiO2 particles (Aeroperl 200, Parteck SLC 500, Syloid XDP 3050, Syloid XDP 3150, Syloid 244 FP, Syloid AL-1 FP) were evaluated in terms of particle morphology and size, specific surface area, pore volume and size, flowability and water content and affinity. It was seen that these properties vary among different kinds of particles, but the optimal kind to use in solid dispersion is mostly dependant on the purpose of the study and formulation design. Our systematic literature review of two different databases yielded 60 articles which complied with the purpose of our study. It was seen that scientists use many different active pharmaceutical ingredients belonging to various therapeutic groups, which are most often incorporated into SiO2 types with small particles and bigger pores, such as Sylysia 350 and Syloid 244 FP. Furthermore, a lot of different methods are used to produce solid dispersions, with the most common being solvent evaporation methods. In most of the articles, the acquired solid dispersions were in completely or mostly amorphous form, which mostly remained stable at the specific test conditions. Almost every research also reported on improved solubility by formulating a solid dispersion; in some cases, only dissolution rate was enhanced, but many times, the percentage of the dissolved drug was also increased. There were only a few articles dealing with producing a finished dosage form and confirming in vitro measurements with in vivo results. In finished dosage forms, which were most commonly tablets, the drug content was mostly very low due to the poor tabletting properties of pure solid dispersions. In in vivo testing, solid dispersions contributed to improved pharmacokinetic properties of the drug. In future, it would probably be reasonable to conduct more research, where the aim would be to develop a formulation that could someday also find its place in the market.

• Ključne besede: solid dispersions, mesoporous silica materials, literature review, solubility and dissolution rate enhancement