Izdelava in vrednotenje hidrofilnih nanovlaken z ibuprofenom

Zemljak, Jaka (author), Kocbek, Petra (mentor)

Večina novo odkritih zdravilnih učinkovin je slabo topnih v vodi. Na biološko uporabnost slabo topne in dobro permeabilne zdravilne učinkovine lahko vplivamo s povečanjem hitrosti raztapljanja in/ali topnosti. To lahko dosežemo z vgradnjo zdravilne učinkovine v hidrofilna nanovlakna. Povečana specifična površina in močenje izboljšata stik med topljencem in topilom. Amorfne oblike zdravilnih učinkovin ponavadi izkazujejo večjo topnost kot kristalne oblike. Povečanje stične površine in topnosti skladno z Noyes-Whitneyevo enačbo poveča hitrost raztapljanja. Nanovlakna smo izdelali iz etanolne raztopine polietilenoksida, poloksamera 407 in ibuprofena. V raztopine smo kot zaviralec obarjanja dodali Soluplus, hidroksipropilmetilcelulozo (HPMC) 606 ali HPMC 615. Iz polimernih raztopin smo nanovlakna izdelali z metodo elektrostatskega sukanja. Morfologijo izdelanih nanovlaken smo proučili z vrstično elektronsko mikroskopijo ter izvedli analizo topnosti in sproščanja ibuprofena iz nanovlaken. Iz vseh polimernih raztopin so nastala nanovlakna. Iz formulacije brez zaviralca obarjanja in iz formulacije z dodatkom HPMC 615 so nastala gladka nanovlakna, brez morfoloških posebnosti. Nanovlakna z dodanim HPMC 606 so imela v strukturi večje odebelitve, nanovlakna s Soluplusom pa so bila nitasto razcepljena. Nanovlaknom različnih formulacij smo določili povprečni premer in standardno deviacijo premera. Profili sproščanja ibuprofena iz različnih formulacij nanovlaken so bili med seboj podobni. Iz vseh formulacij se je ibuprofen takoj sprostil, in sicer se je v prvih 5 minutah sprostilo 90 % zdravilne učinkovine. Ugotovili smo, da dodatek HPMC 606 ne omogoči stabilizacije prenasičenega stanja, medtem ko dodatek Soluplusa učinkovito poveča topnost ali stabilizira prenasičeno stanje (vsaj 24 h). Iz rezultatov raziskave lahko zaključimo, da dodatek Soluplusa v nanovlakna omogoči učinkovito vzdrževanje prenasičenja ali povečanje topnosti učinkovine. Nadaljne raziskave bi bilo smiselno usmeriti v optimizacijo formulacije z dodatkom Soluplusa, da bi bila izdelava bolj ponovljiva in prilagoditi sestavo nanovlaken tako, da bi povečali delež ibuprofena in zmanjšali delež Soluplusa v formulaciji.

• Language: Slovenian
• Keywords: ibuprofen, nanovlakna, elektrostatsko sukanje, topnost, prenasičenje
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2020
• PID: 20.500.12556/RUL-121653
• Publication date in RUL: 21.10.2020

Secondary language

• Language: English
• Title: Preparation and characterization of hydrophilic nanofibers containing ibuprofen

Abstract

Majority of newly discovered active substances are poorly soluble in water. Bioavailability of a poorly soluble drug with good permeability can be modified by increasing its dissolution rate and/or solubility. This can be achieved by incorporation of the drug in hydrophilic nanofibers. Increased specific surface area and better wetting improve the contact between solute and solvent. Amorphous forms of active ingredients usually exhibit higher solubility than their crystalline forms. The increase in contact surface and solubility improves dissolution rate according to the Noyes-Whitney equation. Nanofibers were produced from ethanol solutions of poly(ethylene oxide), poloxamer 407 and ibuprofen. A precipitation inhibitor, namely Soluplus, hydroxypropyl methylcellulose (HPMC) 606 or HPMC 615, was added to the solutions. Nanofibers were prepared from the polymer solutions by electrospinning. The morphology of the produced nanofibers was studied by scanning electron microscopy. The analysis of ibuprofen solubility and release from the nanofibers were also performed. Nanofibers were formed from all polymer solutions. Smooth nanofibers without any artifacts in morphology were produced from the formulation without precipitation inhibitor and from the formulation with the addition of HPMC 615. Addition of HPMC 606 resulted in beaded nanofibers and nanofibers with Soluplus were in the form of discontinuous cylinders that were interconnected with thin filaments. The average diameter and standard deviation of the diameter of different nanofiber formulations were determined. The release profiles of ibuprofen from different nanofiber formulations were similar. Ibuprofen was immediately released from all formulations as 90% of the active substance was released within the first 5 minutes. The results revealed that the addition of HPMC 606 does not stabilize the supersaturated state, while the addition of Soluplus effectively increases solubility or stabilizes the supersaturation (24 h or longer). Based on the results of this study we can conclude that the addition of Soluplus facilitates efficient supersaturation or an increase in drug solubility. Further research should be focused on optimization of the nanofiber formulation with Soluplus to improve the reproducibility of the production process and to modify the composition to increase the drug loading and decrease the amount of Soluplus in the formulation.

• Keywords: ibuprofen, nanofibers, electrospinning, solubility, supersaturation