Razvoj formulacije in vrednotenje sproščanja valsartana iz bukalnih filmov

Končan, Vesna (author), Planinšek, Odon (mentor), Grilc, Blaž (co-mentor)

Valsartan se po peroralni aplikaciji obsežno metabolizira pri prehodu skozi jetra. Učinkovino s takšnimi lastnostmi lahko vgradimo v bukalne filme, ki so alternativa klasičnim peroralnim farmacevtskim oblikam zaradi dobre absorpcije skozi bukalno sluznico. Pri razvoju bukalnih filmov smo za pomožne snovi uporabili mukoadhezivni nosilni polimer natrijev alginat in različna mehčala, ki izboljšajo mehanske lastnosti ter zmanjšujejo njihovo krhkost. Zaradi slabše topnosti valsartana smo zdravilno učinkovino med izdelavo filmov pretvorili v natrijevo sol in uporabili sotopilo etanol. Bukalne filme smo izdelali z metodo nanašanja filmske mase na trdno podlago, njihovo debelino smo nastavili z ustreznim aplikatorjem. Med vsemi formulacijami smo izbrali štiri, ki so izkazovale najboljše mehanske lastnosti, in jih podrobneje ovrednotili. Vsebnost učinkovine v posameznem filmu je znašala 8-10 mg. Dodatno smo pripravili tudi dva filma z višjo vsebnostjo valsartana (12-15 mg). Za izdelane formulacije smo izvedli teste sproščanja na napravi s košarico (USP I), veslom (USP II) in modificirani pretočni celici (USP IV). Rezultate sproščanj smo primerjali s profili nove inovativne pretočne celice za sproščanje (IPCS), ki je bila razvita na Katedri za farmacevtsko tehnologijo. Prepoznali smo zmožnosti posamezne metode za vrednotenje sproščanja zdravilne učinkovine iz bukalnih filmov. Za vrednotenje polimorfne oblike vgrajene ZU smo uporabili diferenčno dinamično kalorimetrijo in infrardečo spektroskopijo s Fourierjevo transformacijo. Slike bukalnih filmov smo zajeli s presevnim in stereo-mikroskopom in jih ovrednotili s slikovno analizo. Z nevronsko mrežo Inception v3 smo pretvorili slike v številski format in razporedili filme v kakovostne razrede. Zaradi krušljivega roba in beline je najbolj izstopala formulacija z manitolom. Izstopala je tudi formulacija z višjim deležem valsartana, ki smo ga namensko pripravili v kristalni obliki in je bila že na pogled drugačna od ostalih. Z rezultati smo potrdili primernost metode za objektivno vrednotenje vizualne kakovosti bukalnih filmov.

• Language: Slovenian
• Keywords: bukalni filmi, valsartan, sproščanje, polioli, slikovna analiza
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2021
• PID: 20.500.12556/RUL-132050
• Publication date in RUL: 10.10.2021

Secondary language

• Language: English
• Title: Formulation development and valsartan release evaluation from buccal films

Abstract

Valsartan is extensively metabolized by passage through the liver after oral administration. Buccal films are emerging as an alternative to conventional oral dosage forms due to their good absorption through the buccal mucosa. The mucoadhesive carrier polymer sodium alginate, the active ingredient valsartan, and various plasticizers have been used as excipients in buccal films to improve the mechanical properties and reduce the brittleness of the films. Due to the lower solubility of valsartan, the active pharmaceutical ingredient was converted to a sodium salt in the preparation of the films, and ethanol was used as a co-solvent to homogenize the particle size and improve the solubility of the active pharmaceutical ingredient. The buccal films were prepared by the solvent casting method and their thickness was adjusted with an applicator. From all formulations, the four that showed the best mechanical properties were selected and studied in more detail. The content of active ingredient in each film was 8-10 mg. Additionally, two films with a higher valsartan content (12-15 mg) were prepared. We also prepared two films with a higher valsartan content. These two contained a higher proportion and different polymorphic forms of the active pharmaceutical ingredient (API). The prepared formulations were subjected to release tests on a basket (USP I), paddle (USP II), and modified flow cell device (USP IV). The release results were compared with the profiles of the new Innovative Release Flow Cell developed in the Pharmaceutical Technology department. We identified the potential of each method to evaluate the release of API from buccal films. Differential scanning dynamic calorimetry and infrared spectroscopy were used to evaluate the polymorphic form of the incorporated API. Images of buccal films were acquired using transmission microscope and stereo microscope and evaluated by image analysis. We converted the images to a numerical format using the Inception v3 neural network and classified the films into quality classes. Due to the crunchy edge and whiteness, the mannitol formulation stood out the most. The formulation with a higher proportion of valsartan also stood out, which was purposely prepared in crystalline form and was already different from the others. The results confirmed the suitability of the method for objective evaluation of the visual quality of buccal films.

• Keywords: buccal films, valsartan, release, polyols, image analysis