Razvoj in vrednotenje liotropnih tekočih kristalov na osnovi glicerol monolinoleata za subkutano aplikacijo

Janežič, Nina (avtor), Zvonar Pobirk, Alenka (mentor), Vitek, Mercedes (komentor)

Tekoči kristali so snovi, ki imajo lastnosti trdne snovi in tekočine. Liotropni tekoči kristali lahko izkazujejo različne mezofaze, ki se med seboj razlikujejo po urejenosti molekul. Glede na to ločimo lamelarne, heksagonalne in kubične mezofaze. Heksagonalne in kubične mezofaze zaradi specifične mikrostrukture raziskujejo predvsem za namen subkutane aplikacije za podaljšano sproščanje zdravilnih učinkovin. V okviru magistrske naloge smo z izbranimi pomožnimi snovmi razvili tekoče brezvodne formulacije, ki so primerne za injiciranje in iz katerih ob stiku z vodnim medijem nastane gel z mikrostrukturo heksagonalnih oziroma kubičnih tekočih kristalov. Kot lipidno fazo smo uporabili glicerol monolinoleat, ki je primeren za injiciranje in ima sposobnost tvorbe heksagonalnih oziroma kubičnih mezofaz ob stiku z vodnim okoljem. Kot hidrotropno snov smo uporabili etanol oziroma etanol in lecitin kot zmes hidrotropne snovi in emulgatorja. V prvem sklopu dela smo izdelali dva (psevdo)trikomponentna diagrama, s pomočjo katerih smo na podlagi opazovanja organoleptičnih lastnosti določili potencialna področja nastanka tekočih kristalov. Nastanek tekočih kristalov smo nato potrdili oziroma ovrgli z metodo polarizacijske mikroskopije pri 25 °C (sobna temperatura) in 37 ° C (telesna temperatura). V drugem delu naloge smo nabor najbolj optimalnih formulacij, iz katerih so ob stiku z vodnim okoljem nastali pretežno heksagonalni oziroma kubični tekoči kristali, zožili na naslednje sisteme: (E/L)Gl20, (E/L)Gl30, (E/L)Gl40 in (E/L)Gl50. Tem sistemom smo v nadaljevanju z vrednotenjem injektabilnosti, časa geliranja, sposobnosti geliranja, privzema vode in z meritvami reologije določili funkcionalne lastnosti, ki so pomembne za subkutano aplikacijo. Vse štiri formulacije so bile injektabilne in so po stiku z vodnim okoljem tvorile gel in situ. Za namen subkutane aplikacije pa se je glede na hidratacijo in reološke lastnosti kot najbolj obetavna izkazala formulacija (E/L)Gl50, ki predstavlja potencialen dostavni sistem za subkutano aplikacijo za podaljšano sproščanje zdravilnih učinkovin.

• Jezik: Slovenski jezik
• Ključne besede: heksagonalni tekoči kristali, kubični tekoči kristali, glicerol monolinoleat, subkutana aplikacija, podaljšano sproščanje
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2023
• PID: 20.500.12556/RUL-151828
• Datum objave v RUL: 21.10.2023

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Development and characterization of glycerol monolinoleate-based lyotropic liquid crystals for subcutaneous application

Izvleček

Liquid crystals are substances that have the properties of both a solid and a liquid. Lyotropic liquid crystals can exhibit different mesophases, which differ from each other in terms of molecular arrangement. Based on this, lamellar, hexagonal and cubic mesophases are distinguished. Due to their specific microstructure, hexagonal and cubic mesophases are mainly being studied for the purpose of subcutaneous application for prolonged release of active substances. As part of the master's thesis, we developed liquid anhydrous formulations with selected excipients that are suitable for injection and from which a gel with a microstructure of hexagonal or cubic liquid crystals is formed upon contact with an aqueous medium. Glycerol monolinoleate was used as the lipid phase, which is suitable for injection and can form hexagonal or cubic mesophases upon contact with an aqueous environment. We used ethanol as a hydrotropic substance, or ethanol and lecithin as a mixture of a hydrotropic substance and an emulsifier. In the first part, we constructed two (pseudo)three-component diagrams and based on the observation of organoleptic properties, we determined the potential areas of formation of liquid crystals. The formation of liquid crystals was then confirmed or refuted by the method of polarization microscopy at 25 °C (room temperature) and 37 °C (body temperature). In the second part, we narrowed down the set of the most optimal formulations, from which predominantly hexagonal or cubic liquid crystals were formed upon contact with water environment, to the following systems: (E/L)Gl20, (E/L)Gl30, (E/L) Gl40 and (E/L)Gl50. For these systems, we further evaluated the functional properties that are important for subcutaneous application, such as injectability, gelation time, water uptake and rheological properties of the selected samples and performed a gelation test. All four formulations were injectable and formed an in situ gel after contact with aqueous environment. For the purpose of subcutaneous application, the formulation (E/L)Gl50 proved to be the most promising in terms of hydration and rheological properties, representing a potential delivery system for subcutaneous application for prolonged release of active substances.

• Ključne besede: hexagonal liquid crystals, cubic liquid crystals, glycerol monolinoleate, subcutaneous application, prolonged release