Razvoj bukalnih polimernih filmov za sistemsko dostavo zdravilnih učinkovin in diskriminatorne in vitro metode sproščanja

Grilc, Blaž (avtor), Planinšek, Odon (mentor)

Nenehen razvoj zdravil je ključen pri spopadanju z boleznimi sodobnega sveta. Majhen košček k temu razvoju predstavlja tudi doktorsko delo, v katerem smo sistematično predstavili področje bukalnih filmov in se poglobili v njihovo formuliranje. Filmi za bukalno aplikacijo so mukoadhezivne farmacevtske oblike, ki so namenjene sistemski ali lokalni dostavi ZU. Njihova lastnost je, da se oprimejo sluznice v ustih in tam sprostijo zdravilno učinkovino (ZU). Izdelava takšnih formulacij zahteva dodatna znanja, ki smo jih pridobili med razvojem bukalnih filmov. Razvoja filmov smo se lotili večplastno. Sprva smo poiskali primerne ZU za bukalno dostavo. Osredotočili smo se na ZU z nizko biološko uporabnostjo in z nizkimi odmerki. Določili smo prednosti filmov s temi ZU pred konvencionalnimi zdravili. Filme smo razvijali sistematično s pomočjo statističnih metod. Z namenom, da bi določili najbolj primerne procesne parametre in optimalno kvantitativno sestavo filma, smo si pomagali s pristopi načrtovanja eksperimentov. Predstavili in preizkusili smo različne metode za vrednotenje tankoslojnih filmov in potrdili skladna opažanja z drugimi raziskovalci o specifičnosti tovrstnih farmacevtskih oblik. Za njihovo vrednotenje je na voljo malo metod, ki bi dajale aplikativne rezultate. Naslovili smo izziv sproščanja ZU iz bukalnih filmov z razvojem lastne metode sproščanja ICRF (Innovative cell for release of films). To metodo smo podrobno ovrednotili in jo primerjali z drugimi sistemi, ki jih najpogosteje zasledimo v literaturi. Potrdili smo, da je dvostransko vrednotenje sproščanja ZU iz filmov primernejše od enostranskega, saj je bolj primerljivo z in vivo pogoji. Posvetili smo se formuliranju filmov z valasartanom in metoklopramidom. Filme smo pripravili z ZU v amorfni in kristalni obliki ter vrednotili njihove lastnosti. Med razvojem formulacij smo prepoznali pomembnost opazovanja videza filmov, saj ta vsebuje veliko informacij o njihovi kakovosti. Poseben izziv predstavlja vrednotenje abstraktnih pojavov, kot so pokanje filma med sušenjem, pojav kristalizacije ZU in ocena homogenosti filma. Vrednotenje teh lastnosti, smo preučevali z uporabo strojne analize slik z nevronsko mrežo. To je odprlo nove možnosti za preučevanje in kvantitativno vrednotenje bukalnih filmov. Področje bukalnih filmov je zaradi ozkega nabora primernih ZU med bolj zapostavljenimi raziskovalnimi področji. Zaradi številnih prednosti tega dostavnega sistema njihov razvoj še vedno vzbuja zanimanje med raziskovalci.

• Jezik: Slovenski jezik
• Ključne besede: bukalni filmi, sproščanje zdravilnih učinkovin, kristalizacija, slikovna anliza, pretočna celica
• Vrsta gradiva: Doktorsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2024
• PID: 20.500.12556/RUL-161089
• Datum objave v RUL: 07.09.2024

GRILC, Blaž, 2024, Razvoj bukalnih polimernih filmov za sistemsko dostavo zdravilnih učinkovin in diskriminatorne in vitro metode sproščanja [na spletu]. Doktorska disertacija. [Dostopano 7 april 2025]. Pridobljeno s: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=slv&id=161089

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Development of polymer buccal films for systemic administration of active pharmaceutical ingredients and discriminatory in vitro release method

Izvleček

Continuous development is the key to managing disease in the modern lifestyle. This doctoral thesis, in which we have systematically presented the field of buccal films and dealt with their formulation, also represents a small piece of this development. Buccal films are mucoadhesive pharmaceutical forms intended for systemic or local drug delivery. They are characterized by the fact that they adhere to the mucous membranes in the mouth and release the active ingredient there. The production of such formulations requires additional knowledge acquired in the development of buccal films. We approached the development of the films in different ways. First, we searched for suitable drugs for buccal administration. We focused on drugs with low bioavailability and low dosage. We determined the advantages of films containing these drugs over conventional drugs. We systematically developed the films using statistical methods. We used experimental design approaches to determine the most suitable process parameters and the optimal quantitative composition of the film. We presented and tested different methods for the evaluation of thin films, confirming consistent observations with other researchers about the specificity of such dosage forms. There are few methods for their evaluation that would provide applicable results. We have addressed the challenge of drug release from buccal films by developing our own innovative cell for release of films (ICRF) release method. We evaluated this method in detail and compared it with other systems. We confirmed that two-sided release of films is more suitable than one-sided release as it is more comparable to in vivo conditions. We addressed the formulation of films with valasartan and metoclopramide. We prepared films with the drug in amorphous and crystalline form and evaluated their properties. During the development of the formulations, we realized how important it is to observe the appearance of the films, as this contains a lot of information about their quality. A particular challenge is the evaluation of abstract phenomena such as the cracking of the film during drying, the phenomenon of drug crystallization and the evaluation of the homogeneity of the film. The evaluation of these properties was approached using machine image analysis with a neural network. This opened up new possibilities for the examination and quantitative evaluation of buccal films. The field of buccal films is one of the neglected areas of research, as the selection of suitable drugs is limited. Nevertheless, this direction of pharmaceutical development continues to attract the interest of researchers due to the many advantages of this delivery system.

• Ključne besede: buccal films, drug release, crystallization, image analytics, flow cell