Vrednotenje vpliva učinkovin na lastnosti hidrofilnih polimernih filmov

Femc, Tjaša (author), Kocbek, Petra (mentor), Dragar, Črt (comentor)

Polimerni filmi, izdelani iz hidrofilnih polimerov, se pogosto uporabljajo kot orodisperzibilni filmi, ki predstavljajo bolniku prijazno farmacevtsko obliko. Aplicirajo se na sluznico ustne votline in se ob stiku s slino dispergirajo, zdravilna učinkovina pa se hitro sprosti in deluje lokalno ali se absorbira v sistemski krvni obtok. V polimerne filme lahko vgradimo zdravilne učinkovine, ki imajo različne fizikalno-kemijske lastnosti, kar lahko pomembno vpliva na lastnosti polimernih filmov. Namen magistrske naloge je bil ovrednotiti vpliv štirih različnih zdravilnih učinkovin (ibuprofena, karvedilola, paracetamola in metforminijevega klorida) na lastnosti hidrofilnih polimernih filmov. Polimerne filme z 20 % (m/m) zdravilne učinkovine smo pripravili z metodo izhlapevanja topila iz etanolne raztopine zmesi polietilenoksida in poloksamera 188 v masnem razmerju 1 : 1. Ugotovili smo, da je dinamična viskoznost polimerne raztopine z zdravilno učinkovino nižja kot dinamična viskoznost polimerne raztopine brez zdravilne učinkovine. Pri vseh polimernih raztopinah smo izmerili višje vrednosti plastičnega modula od vrednosti elastičnega modula in nizko električno prevodnost. Izjema je bila polimerna raztopina z metforminijevim kloridom, ki je imela visoko električno prevodnost. Ugotovili smo, da dodatek zdravilne učinkovine v polimerne filme pomembno vpliva na morfologijo površine polimernih filmov, saj lahko vodi do nagubanosti in nastanka razpok v površini polimernih filmov. Ugotovili smo tudi, da med komponentami polimernih filmov ne prihaja do kemijskih interakcij. Vsebnost vlage v vseh izdelanih polimernih filmih je bila po 24 h pri sobni temperaturi in pri relativni vlažnosti 46 % < 1 % (m/m), s čimer smo potrdili, da vgrajene zdravilne učinkovine ne vplivajo pomembno na higroskopnost izdelanih polimernih filmov. Dokazali smo, da hidrofobne zdravilne učinkovine (ibuprofen, karvedilol) zmanjšajo hidrofilnost površine, medtem ko vpliv hidrofilnih zdravilnih učinkovin (paracetamol, metforminijev klorid) ni predvidljiv. Vgrajene zdravilne učinkovine niso pomembno vplivale na čas dispergiranja polimernih filmov v fosfatnem pufru z 0,1 % (m/V) Tween® 80 ali v vodi, pomembno pa so podaljšale čas dispergiranja polimernih filmov v etanolu. Z vgradnjo karvedilola v polimerni film smo dosegli hitrejše sproščanje karvedilola v primerjavi z njegovim raztapljanjem iz fizikalne zmesi. Hitrost sproščanja ostalih proučevanih zdravilnih učinkovin (ibuprofen, paracetamol, metforminijev klorid) iz polimernih filmov je bila primerljiva s hitrostjo raztapljanja teh zdravilnih učinkovin iz fizikalne zmesi.

• Language: Slovenian
• Keywords: Dispergiranje, hidrofilni polimerni filmi, površinske lastnosti, sproščanje zdravilne učinkovine, vsebnost zdravilne učinkovine.
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2023
• PID: 20.500.12556/RUL-151952
• Publication date in RUL: 26.10.2023

Secondary language

• Language: English
• Title: Evaluation of drug impact on the properties of hydrophilic polymer films

Abstract

Polymer films made from hydrophilic polymers are often used as orodispersible films, which represent a patient-friendly pharmaceutical form. They are applied to the mucous membrane of the oral cavity and disperse after their contact with saliva, leading to a quick drug release and its absorption into the systemic bloodstream. Drugs with different physicochemical properties can be incorporated into polymer films and this can have a significant impact on the properties of the polymer films. The aim of the master's thesis was to evaluate the impact of four different drugs (ibuprofen, carvedilol, paracetamol, and metformin hydrochloride) on the properties of hydrophilic polymer films. Polymer films with 20% (w/w) drug content were prepared by the solvent evaporation method from an ethanol solution of a mixture of polyethylene oxide and poloxamer 188 in a mass ratio of 1:1. We found that dynamic viscosity of the polymer solutions with drug is lower than dynamic viscosity of the polymer solutions without drug. For all polymer solutions, we measured higher values of the plastic modulus than the value of the elastic modulus and low electrical conductivity. The exception was the polymer solution with metformin hydrochloride, which had high electrical conductivity. We found that the incorporation of the drug into polymer films significantly affects their surface morphology, as it can lead to wrinkling and the formation of cracks on the surface of the polymer film. No chemical interactions between the components of the polymer films were found. The moisture content in the produced polymer films after 24 hours at room temperature and 46% relative humidity was < 1% (m/m), which confirmed that the incorporated drugs do not affect the hygroscopicity of the polymer films. We proved that hydrophobic drugs (ibuprofen, carvedilol) decrease the hydrophilicity of the surface, while the effect of hydrophilic drugs (paracetamol, metformin hydrochloride) is unclear. The incorporated drugs did not affect the dispersibility of polymer films in phosphate buffer with 0,1% (m/V) Tween® 80 or in the water, while the dispersion time of polymer films in ethanol was significantly prolonged. By incorporating carvedilol into the polymer film, a faster release rate of carvedilol was achieved compared to dissolution of carvedilol from a physical mixture. The release rate of other drugs (ibuprofen, paracetamol, metformin hydrochloride) from the polymer films was similar to the dissolution rate of these drugs from the physical mixture.

• Keywords: Dispersing, drug content, drug release, hydrophilic polymer films, surface properties.