Migracija vode v zmesi farmacevtske učinkovine in pomožnih snovi

diplomsko delo visokošolskega strokovnega študijskega programa I. stopnje

Maša Krakar (Avtor), Zoran Novak (Mentor), Gabrijela Tkalec (Komentor), Boštjan Jerman (Komentor)

Povzetek

V diplomski nalogi smo raziskovali migracijo vode v zmeseh farmacevtske učinkovine (XN) in pomožnih snovi (PS). Uporabili smo XN in pet pomožnih snovi (škrob koruzni sušen, mikrokristalinično celulozo, brezvodno laktozo, laktozo monohidrat in manitol), katere smo izbrali po principu higroskopnih lastnosti in različnih energij vezave vode. Da bi razumeli vpliv vsebnosti vode in vodne aktivnosti na strukturo snovi, smo na začetku posamezne pomožne snovi in zmesi analizirali s tehnikami DSC, TGA, vodna aktivnost (aw) in dinamična sorpcija vode (DVS). Razen XN, ki je kazala fizikalno nestabilnost pri visokih stopnjah relativne vlažnosti (RV) in je prešla v novo kristalno (hidratno) obliko, so bile ostale snovi fizikalno stabilne. Potem smo pripravili fizikalne zmesi 1:1, XN : pomožna snov, jih za dva tedna zaprli v neprodušno zaprto vialo, da je potekal prenos vode med snovmi do ravnotežnih vrednosti in nato zmesi analizirali z aw, DSC in TGA. Pri zmeseh, kjer smo detektirali strukturno spremembo, smo posneli še Raman in Rentgensko praškovno analizo. Tekom eksperimenta smo oblikovali komoro za izmenjavo vode preko parne faze med fizično ločenimi komponentami. Uporabili smo velike steklene tehtiče, v katere smo vstavili dve aluminijasti ladjici, v prvo smo zatehtali XN in v drugo pomožno snov (1:1 w/w). Steklene tehtiče smo nato zaprli s steklenim pokrovom, katerim smo obrus dodatno zatesnili s silikonsko mastjo. Tak zaprt sistem je pri sobnih pogojih omogočal prehajanje vode le med obema vzorcema v tehtiču preko parne faze, na nekontakten način. Po 2 tednih smo analizirali vsebnost vode in vodno aktivnost v obeh eksperimentih. Z meritvijo vodne aktivnosti smo pri 1:1 in 1:3 (W/W) kontaktnih in nekontaktnih zmeseh preučili smer in obseg migracije vode. Pri kontaktnih zmeseh smo dokazali eno od hipotez naloge, in sicer da voda migrira iz snovi z višjo vodno aktivnostjo v snov z nižjo vodno aktivnostjo. V primeru mešanic navlaženih PS (škrob, MCC in XN), ki so vsebovale povečano vsebnost nevezane in šibko vezane vode, smo ugotovili, da je bila količina izmenjane vode med PS in XN v smeri XN tako velika, da je prišlo do vgradnje vode v kristalno strukturo XN in nastanka nove pojavne oblike XN, hidratne oblike, natančneje hemihidrata, kar smo potrdili z naborom komplementarnih analiznih tehnik (DSC, TGA, XRPD, Raman). Skupaj s posnetimi sorpcijskimi izotermami smo lahko napovedali smer migracije in količino migrirane vode za vsako posamezno komponento. Na podlagi ugotovljenih rezultatov smo tako lahko razvili delni protokol za izbor PS, ki jih dodamo farmacevtski učinkovini, ki kaže tendenco prehajanja v hidratne oblike ob prisotnosti povečane vsebnosti nevezane ali šibko vezane vode. Protokola se bomo posluževali pri razvoju novih izdelkov, v katere bomo vgrajevali učinkovine, ki imajo podobne lastnosti kot XN.

Ključne besede

farmacevtske učinkovine;sorpcija;migracija vode;vsebnost vode;vodna aktivnost;fizikalna stabilnost;hidrati;diplomske naloge;

Podatki

Jezik:	Slovenski jezik
Leto izida:	2023
Tipologija:	2.11 - Diplomsko delo
Organizacija:	UM FKKT - Fakulteta za kemijo in kemijsko tehnologijo
Založnik:	[M. Krakar]
UDK:	615.011:66.093.4(043.2)
COBISS:	148475395
Št. ogledov:	49
Št. prenosov:	6
Ocena:	0 (0 glasov)
Metapodatki:

Ostali podatki

Sekundarni jezik:	Angleški jezik
Sekundarni naslov:	Water migration in a mixture of active pharmaceutical substance and excipients water migration in a mixture of active pharmaceutical substance and excipients
Sekundarni povzetek:	In the presented diploma thesis, we investigated water migration in mixtures of the active pharmaceutical ingredient (XN) and its excipients (PS). We used XN and five excipients (dried corn starch, microcrystalline cellulose, anhydrous lactose, crystalline lactose, and mannitol), which were chosen based on the principle of hygroscopic properties and different water binding energies. To understand the influence of water content and water activity on the substance's structure, we first characterized individual excipients and mixtures using DSC, TGA, water activity (aw), and dynamic water sorption (DVS) techniques. Except for XN, which showed physical instability at high relative humidity levels (RV) and changed to a new crystalline (hydrate) form, the other substances were physically stable. Then we prepared physical mixtures 1:1, XN: excipient, and closed them in an airtight sealed vial for two weeks so that the transfer of water between the substances took place to equilibrium values, and then the mixtures were analyzed by aw, DSC, and TGA. In the case of mixtures where a structural change was detected, Raman and X-ray powder analysis were also recorded. During the experiment, we designed a chamber for water exchange through the vapor phase between physically separated components. We used a large glass crucible / weighing bottle into which we inserted two aluminum vessels. We weighed XN in the first vessel and the excipient (1:1 w/w) in the second one. We then closed the glass scales with a glass cover that was additionally sealed with silicone grease. Under room conditions, this exact closed system allowed water to pass only between the two samples in the crucible through the vapor phase in a non-contact manner. After 2 weeks, we analyzed the water content and water activity in both experiments. By measuring the water activity, we examined the direction and extent of water migration in 1:1 and 1:3 (W/W) contact and non-contact mixtures. In the case of contact mixtures, we proved one of the hypotheses of the thesis - the water migrates from substances with higher water activity to a substance with lower water activity. In the case of mixtures with moistened PS (starch, MCC, and XN) that contained an increased content of unbound and weakly bound water, we found that the amount of water exchanged between PS and XN in the XN direction was so large that it resulted in the incorporation of water in the crystal structure of XN, and also the formation of a new form of XN. This was a hydrate form, more precisely, the hemihydrate, confirmed by a set of complementary analytical techniques (DSC, TGA, XRPD, Raman). Along with the obtained sorption isotherms, we were able to predict the direction of migration and the amount of migrated water for each component. Based on the established results, we were able to develop a protocol for the selection of PS, added to XN, which shows a tendency to transition into hydrate forms in the presence of an increased unbound or weakly bound water We will use the protocol in the development of new products with active ingredients that have similar properties to XN.
Sekundarne ključne besede:	active pharmaceutical ingredient;water sorption;water migration;water content;water activity;physical stability;hydrate forms;
Vrsta dela (COBISS):	Diplomsko delo/naloga
Komentar na gradivo:	Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo
Strani:	1 spletni vir (1 datoteka PDF (X, 45 f.))
ID:	18204034