Razvoj peroralnega organogela iz nanoceluloze z atorvastatinom

Car, Tjaša (author), Gašperlin, Mirjana (mentor), Bolko Seljak, Katarina (co-mentor)

Peroralna aplikacija predstavlja najprimernejši in najprijaznejši način jemanja zdravil. A danes velik delež na novo odkritih zdravilnih učinkovin (ZU) izkazuje slabo vodotopnost in/ali slabo permeabilnost, ki nakazujeta slabo biološko uporabnost slednjih pri peroralni aplikaciji. Posledično je zadnja leta naraslo zanimanje za lipidne dostavne sisteme, ki omogočajo aplikacijo teh ZU v že raztopljeni obliki, kar pripelje do večje absorpcije in biološke uporabnosti slabo vodotopnih ZU. Prav tako je družba prepoznala pomen varovanja okolja in našega planeta. V tem ne zaostaja niti farmacevtska industrija, ki poskuša v čim večji meri vpeljati obnovljive in biološko razgradljive vire surovin. Takšen primer predstavlja kristalinična nanoceluloza (NCC), ki smo jo v naši magistrski nalogi inovativno uporabili kot 3D ogrodje organogela za dostavo ZU. Tekom magistrske naloge smo z indirektno metodo izdelali organogele z različnimi formulacijami, ki so vsebovali atorvastatin kot modelno slabo vodotopno ZU, raztopljeno v tekoči fazi gela. Najprej smo preizkusili, v kateri tekoči oljni fazi izkazuje atorvastatin največjo topnost. Najboljše rezultate smo pridobili v polarnih oljih, sestavljenih iz srednjeverižnih mono- in digliceridov. Tako se je kot najboljši vehikel izkazal Capmul MCM EP. Da je NCC, ki je hidrofilen polimer, lahko s Capmulom MCM EP tvorila organogel, smo vodne disperzije NCC najprej liofilizirali, pogače zmleli in na pridobljen prah nato adsorbirali olje z ZU. Ker je NCC naravni material, ki variira glede na izvor in način pridobivanja, smo liofilizirali NCC dveh proizvajalcev v različnih koncentracijah. V organogele smo uspeli vgraditi 10 mg atorvastatina na 600 mg organogela. Sproščanje atorvastatina iz organogelov smo vrednotili z metodo in vitro sproščanja in in vitro lipolize. Pri tem smo ugotovili, da že aplikacija atorvastatina, raztopljenega v oljni fazi, poveča obseg njegovega sproščanja. Tekom in vitro lipolize je vgradnja atorvastatina v organogel z NCC pomenila večjo količino v vodno fazo sproščenega in tako za absorpcijo pripravljenega atorvastatina, v primerjavi s samo v olju raztopljenim atorvastatinom. V magistrski nalogi nam je uspelo pokazati, da so organogeli z NCC perspektivni dostavni sistemi za slabo vodotopne ZU, s katerimi še izboljšamo sproščanje ZU v primerjavi s samo oljno raztopino (lipidnim dostavnim sistemom tipa I).

• Language: Slovenian
• Keywords: organogel, kristalinična nanoceluloza, atorvastatin, in vitro lipoliza, in vitro sproščanje
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2021
• PID: 20.500.12556/RUL-131343
• Publication date in RUL: 25.09.2021

Secondary language

• Language: English
• Title: Development of nanocellulose oral organogel with atorvastatin

Abstract

Oral administration represents the most appropriate and kindest way to apply medicine. However, a high proportion of newly discovered active ingredients (AI) demonstrate poor water solubility and/or poor permeability, indicating poor bioavailability of the AI when administered orally. As a result, in recent years there has been an increased interest in lipid-based drug delivery systems that allow AIs to be administered in an already dissolved form, leading to higher absorption and bioavailability of poorly water-soluble AIs. Society has also recognized the importance of protecting the environment and our planet. The pharmaceutical industry, which must not fall behind, is trying to introduce renewable and biodegradable sources of raw materials wherever possible. An example of a green material is nanocrystalline cellulose (NCC), which we presented in our master's thesis as an innovatively used 3D cross-linked network of organogel for the delivery of AI. In the master's thesis, organogels with various formulations containing atorvastatin as a model for poorly water-soluble AI dissolved in the liquid phase of the organogel were produced, using the indirect method. First, we tested in which liquid oil phase atorvastatin exhibited maximum solubility. The best results were obtained in polar oils consisting of medium-chain mono- and di-glycerides, so Capmul MCM EP proved to be the best solvent. In order for NCC, which is a hydrophilic polymer, to form an organogel with Campul MCM EP, the aqueous dispersions of NCC were first lyophilized, the cakes ground and the obtained powder was then absorbed with oil containing AI. Since NCC is a natural material that varies according to the origin and method of production, we have lyophilized different aqueous dispersions of NCC, which differ in concentration and were provided by two different manufacturers. We were able to incorporate 10 mg of atorvastatin per 600 mg of organogel. We evaluated the release of atorvastatin from organogels using an in vitro release and in vitro lipolysis. In doing so, we found that the application of atorvastatin dissolved in the oil phase increases the extent of its release. During in vitro lipolysis, the incorporation of atorvastatin in organogel with NCC meant a higher amount in the aqueous phase released and thus for the absorption prepared atorvastatin when compared to oil solution of atorvastatin. In the master's thesis, we were able to show that organogels with NCC are promising delivery systems for poorly water-soluble AI. With organogels, we further improve the release of the AI compared to the oil solution itself (lipid-based drug delivery system - type I).

• Keywords: organogel, nanocrystalline cellulose, atorvastatin, in vitro lipolysis, in vitro release