Vrednotenje stabilnosti in sproščanja betametazondipropionata iz liotropnih tekočih kristalov na osnovi konopljinega ali lanenega olja

Grošelj, Petra (avtor), Gosenca Matjaž, Mirjam (mentor), Vitek, Mercedes (komentor)

Atopijski dermatitis (AD) je najpogostejša nenalezljiva kronična vnetna bolezen kože. Poleg pravilne/ustrezne in redne nege atopijske kože je zelo pomembna tudi lokalna terapija s protivnetnimi zdravilnimi učinkovinami (ZU). Dostavni sistemi z lamelarno strukturo bi, zaradi svoje podobnosti z medceličnimi lipidi rožene plasti lahko predstavljali ugodno podporno terapijo za bolnike z AD in omogočili podaljšano sproščanje protivnetnih ZU, kot je betametazondipropionat (BDP). V okviru magistrske naloge smo proučevali osem sistemov lamelarnih tekočih kristalov (TK) z različno kvali- in kvantitativno sestavo na osnovi konopljinega ali lanenega olja z vgrajenim BDP, in sicer smo izvedi stabilnostno študijo, sproščanje in vitro ter vrednotenje mikrostrukture. V okviru 10-tedenske pospešene stabilnostne študije smo ugotovili, da je stabilnost vgrajenega BDP odvisna predvsem od deleža vode v posameznih formulacijah. Stabilnost BDP je bila najboljša v formulacijah z 30 % deležem vodne faze, najslabša pa v formulacijah z 80 % deležem vodne faze. Izbira emulgatorja je v manjši meri vplivala na stabilnost BDP, ta je bila nekoliko manjša v vzorcih z Montanov 68 v primerjavi z vzorci s Tween 80. Kinetika razgradnje BDP v lamelarnih TK sledi 1. redu. Z metodo ozkokotnega rentgenskega sipanja smo vrednotili mikrostrukturo vzorcev in potrdili prisotnost lamelarnih mezofaz v vseh vzorcih ter tudi micelarne strukture v sistemih z večjim deležem vode in Montanov 68. Z večanjem deleža vodne faze v vzorcih se je povečevala razdalja med lamelami vzorcev. Mikrostrukturo smo ovrednotili pri različnih temperaturah, pomembnih za dermalno dostavo, tj. 25 °C (sobna temperatura), 32 °C (temperatura površine kože) in 37 °C (telesna temperatura). Temperatura ni imela značilnega vpliva na mikrostrukturo vzorcev, kar pomeni, da se ta ohrani tudi po nanosu formulacije na kožo. Prav tako vgradnja BDP ni vplivala na mikrostrukturo TK. V sklopu sproščanja in vitro, ki smo ga izvedli s pomočjo Franz-ovih difuzijskih celic in Strat-M® membran, smo potrdili podaljšano sproščanje BDP iz vseh osmih formulacij. Na sproščanje BDP je bistveno vplivala mikrostruktura posameznih vzorcev. Iz formulacij z lamelarnimi mezofazami in miceli je bilo sproščanje BDP v 24 h hitrejše in večje ((L/M)Lo80, (L/M)Ko80) kot v ostalih vzorcih. Sproščanje BDP iz formulacij smo primerjali z Beloderm® kremo (vsebnost BDP je enaka kot v TK in znaša 0,64 mg/g formulacije) in potrdili večji obseg sproščanja BDP iz vzorcev TK.

• Jezik: Slovenski jezik
• Ključne besede: lamelarni tekoči kristali, atopijski dermatitis, stabilnost, sproščanje, ozkokotno rentgensko sipanje
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2022
• PID: 20.500.12556/RUL-136248
• Datum objave v RUL: 21.04.2022

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Evaluation of betamethasone dipropionate stability and release profile from hemp seed or flaxseed oil-based lyotropic liquid crystals

Izvleček

Atopic dermatitis (AD) is the most common non-infectious chronic inflammatory skin disease. In addition to suitable and regular care of atopic skin, local therapy with anti-inflammatory drugs is of crucial importance. Due to their similarity to the intercellular lipids of the stratum corneum, delivery systems with lamellar structure could provide a favourable supportive therapy for patients with AD in addition to prolonged release of anti-inflammatory drugs such as betamethasone dipropionate (BDP). Within the scope of this Master's thesis, eight lamellar liquid crystal (LC) systems with different qualitative and quantitative composition based on hemp or flaxseed oil with incorporated BDP was studied, namely a stability study, in vitro release study and microstructure evaluation were performed. As observed within the 10-week accelerated stability study the stability of incorporated BDP depends mainly on the water content in individual formulations. BDP stability was the highest in samples with 30 % aqueous phase and the lowest in formulations with 80% aqueous phase. The choice of emulsifier has a minor effect on the stability of BDP, which was slightly lower in the samples with Montanov 68 compared to the samples with Tween 80. The BDP degradation in lamellar LC systems follows the 1st order kinetics. The microstructure of the samples was evaluated by the small angle X-ray scattering analysis with confirmed lamellar mesophases in all samples in addition to micellar structures in systems with higher water content and Montanov 68. The microstructure was evaluated at different temperatures relevant for dermal delivery, i.e. 25 ° C (room temperature), 32 ° C (skin temperature) and 37 ° C (body temperature). The temperature did not have a significant effect on the microstructure of the samples being preserved following skin application. Also, the incorporation of BDP did not affect the LC systems’ microstructure. Prolonged BDP release from all eight systems tested was observed within in vitro release study using Franz diffusion cells and Strat-M® membranes. The BDP release was significantly influenced by the microstructure of individual samples. From formulations with lamellar mesophases and micelles, the release of BDP was faster and higher ((L / M) Lo80, (L / M) Ko80) after 24h compared to other systems. BDP release from LC systems was compared to Beloderm® cream (with same BDP content, i.e. 0,64 mg/g of formulation) and higher release was observed for the LC systems.

• Ključne besede: lamellar liquid crystals, atopic dermatitis, stability, release, small angle X-ray scattering