Vrednotenje sproščanja metoklopramida iz večplastnih bukalnih filmov

Maležič, Gregor (author), Planinšek, Odon (mentor), Grilc, Blaž (comentor)

Metoklopramid je zdravilna učinkovina, ki ima po peroralni aplikaciji zelo spremenljivo biološko uporabnost. Bukalni filmi so novejša farmacevtska oblika, ki ima določene prednosti v primerjavi s peroralnimi oblikami. Z njimi lahko izboljšamo biološko uporabnost in zmanjšamo njeno variabilnost. Bukalne filme smo izdelali z metodo nanašanja filmske mase ob pomoči aplikatorja. Z njim smo uravnavali debelino in enakomeren nanos. Natrijev alginat je imel vlogo nosilnega polimera, ksilitol pa je deloval kot mehčalo. Z metodo načrtovanja eksperimentov smo izdelali 11 različnih formulacij. Spreminjali smo različne deleže sestave in pH. Izdelali smo tudi dvoslojne filme, da bi primerjali vpliv dodatnega usmerjevalnega sloja na profile sproščanja. Dodatni sloj je bil sestavljen iz hidroksipropil celuloze. Za vrednotenje sproščanja smo uporabili dve različni metodi. Prva je bila standardna naprava s košaricami in druga lastna inovativna metoda, ki temelji na pretočni celici. Slednja omogoča boljše razlikovanje med profili sproščanja. Ugotovili smo, da je najpomembnejši dejavnik, ki vpliva na hitrost sproščanja, delež natrijevega alginata. Pri dvoslojnih bukalnih filmih smo opazili precejšnje zmanjšanje hitrosti sproščanja in variabilnosti njihovih profilov. Izdelali smo tudi različne debeline določene formulacije in ugotovili, da z debelejšim usmerjevalnim slojem še dodatno upočasnimo sproščanje in zmanjšamo standardno deviacijo znotraj le teh. Merili smo tudi stične kote vodne kapljice na površini filmov in ugotovili, da nam lahko služijo kot groba ocena sproščanja zdravilne učinkovine. Ugotovili smo, da viskoznost nima vpliva na pojav kristalizacije v filmu in da ima največji vpliv delež ksilitola. Višji delež le tega namreč zavira kristalizacijo zdravilne učinkovine. Nastanek kristalov smo potrdili tudi z ramansko mikroskopijo. Z dodatnim usmerjevalnim slojem pa se kristali zopet raztopijo in filmi postanejo prosojni.

• Language: Slovenian
• Keywords: bukalni filmi, metoklopramid, sproščanje, kristalizacija, načrtovanje eksperimentov.
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2024
• PID: 20.500.12556/RUL-161005
• Publication date in RUL: 06.09.2024

MALEŽIČ, Gregor, 2024, Vrednotenje sproščanja metoklopramida iz večplastnih bukalnih filmov [online]. Master’s thesis. [Accessed 10 April 2025]. Retrieved from: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=eng&id=161005

Secondary language

• Language: English
• Title: Evaluation of metoclopramide release from multilayer buccal films

Abstract

Metoclopramide is an active pharmaceutical ingredient with very variable bioavailability when orally administered. Buccal films are a newer dosage form that offers certain advantages over oral forms. They can improve bioavailability and reduce its variability. We have prepared buccal films using the solvent casting method with help of an applicator. This allowed us to control the thickness and ensure even application. Sodium alginate was used as the carrier polymer, and xylitol acted as a plasticizer. Using the design of experiments (DoE) method, we created 11 different formulations, we varied the proportions of the composition and pH. We also made bilayer films to compare the effect of an additional directing layer on the release profiles. The additional layer consisted of hydroxypropyl cellulose. For the evaluation of release, we used two methods, the first was the standard basket apparatus, and the second was our own innovative method based on a flow cell. The second one allows for better differentiation between release profiles. We found that the most important factor affecting the release rate is the proportion of sodium alginate. In bilayer buccal films, we observed a significant reduction in release rate and the variability of their profiles. We also made different thicknesses of certain formulations and found that a thicker directing layer further slows the release and reduces the standard deviation within them. We also measured contact angles and found that they can serve as a rough estimate of their properties. We found that viscosity does not affect the formation of crystallization and that the proportion of xylitol has the most significant impact. A higher proportion of xylitol results in less crystallization. The formation of crystals was also confirmed by Raman microscopy. With the additional directing layer, the crystals dissolve again, and the films become transparent.

• Keywords: buccal films, metoclopramide, release, crystallization, experimental design.