Izdelava in vrednotenje samo-mikroemulgirajočih sistemov z dolgoverižnimi lipidi : diplomska naloga

Štubljar, Maja (author), Gašperlin, Mirjana (mentor)

Samo-mikroemulgirajoči sistemi (SMES) sodijo med novejše pristope za izboljšanje biološke uporabnosti učinkovin z neustreznimi biofarmacevtskimi lastnostmi po peroralni aplikaciji. Po definiciji so SMES izotropne zmesi lipidov, emulgatorjev, hidrofilnih topil ali koemulgatorjev in učinkovin, ki v stiku z vodo ali vodnim medijem hitro in spontano ob rahlem mešanju tvorijo mikroemulzije tipa O/V. Proces samo-mikroemulgiranja je specifičen za točno določene kombinacije in koncentracijska razmerja lipidov in emulgatorjev. Glavni cilj diplomske naloge je bil izdelati SMES, ki bo po redčenju z vodo ali vodnim medijem tvoril mikroemulzije v najširšem območju (psevdo)trikomponentnega faznega diagrama in hkrati izkazoval največjo topnost in stabilnost za izbrane modelne učinkovine. Za določitev optimalnega razmerja med posameznimi komponentami S(M)ES smo pripravili različne kombinacije lipidnih komponent (ricinusovo olje, laneno olje in PeceolTM) z emulgatorji (Labrasol®, Cremophor® EL in Tween® 20) in koemulgatorji (Cremophor® RH 40, Solutol® HS-15 in CapryolTM 90) ter s titracijsko metodo izdelali (psevdo)trikomponentne fazne diagrame, iz katerih so bila razvidna območja nastanka mikroemulzij. Slednje smo določili na podlagi rezultatov organoleptičnih lastnosti in meritev specifične električne prevodnosti. Ugotovili smo, da so mikroemulzije nastale na najširšem območju (psevdo)-trikomponentnega faznega diagrama iz S(M)ES, ki so vsebovali kot lipidno fazo PeceolTM in ricinusovo ali laneno olje ter emulgator Cremophor® EL. Labrasol® in Tween® 20 sta z izbranimi lipidi omogočila nastanek mikroemulzij le ob visokih koncentracijah in pri nizkih redčitvah z vodo. Po dodatku koemulgatorjev S(M)ES iz ricinusovega olja in PeceolaTM (v razmerju 1:2) ter Cremophor® EL-ja smo opazili signifikantno razširitev območja nastanka mikroemulzij v (psevdo)trikomponentnem faznem diagramu predvsem pri uporabi Cremophor® RH 40-ja. Izbrane S(M)ES smo glede na velikost nastalih dispergiranih kapljic po dodatku vode uvrstili v III razred klasifikacijskega sistema po Poutonu, in sicer so S(M)ES 1-6 ter S(M)ES 8 in 9 tvorili kapljice notranje faze (mikro)emulzij tipa O/V manjše od 100 nm, S(M)ES 7 pa manjše od 250 nm. Torej sodijo prvi med SMES, sistem 7 pa uvrščamo med SES. Nato smo v devetih izbranih S(M)ES določili nasičeno topnost in stabilnost izbranih modelnih učinkovin (NDS 1, NDS 2 in NDS 8). Rezultati kaţejo, da S(M)ES 3, 5 in 8 predstavljajo potencialne sisteme za vgradnjo modelne učinkovine NDS 8, saj smo v njih določili primerno stabilnost učinkovine. Za modelni učinkovini NDS 1 in NDS 2 smo v izbranih S(M)ES sicer določili izredno visoko nasičeno topnost, toda z vidika kemijske stabilnosti modelnih učinkovin pa niso bili ustrezni.

• Language: Slovenian
• Keywords: samomikroemulgirajoči sistemi, lipidni sistem, fazni diagram, SMES
• Work type: Undergraduate thesis
• Typology: 2.11 - Undergraduate Thesis
• Organization: FFA - Faculty of Pharmacy
• Place of publishing: Ljubljana
• Publisher: [M. Štubljar]
• Year: 2012
• Number of pages: IV, 79 f.
• PID: 20.500.12556/RUL-121149
• UDC: 66.091(043.2)
• COBISS.SI-ID: 3197297
• Publication date in RUL: 30.09.2020

Secondary language

• Language: English
• Title: Formulation and evaluation of self-emulsifying systems with long-chain lipids

Abstract

Self-microemulsifying systems (SMES) are among novel approaches for improving oral absorption of drugs with poor biopharmaceutical properties. According to the definition SMES are isotropic mixtures of oils, surfactants, hydrophilic solvents or co-surfactants and drugs that form oil-in-water microemulsions spontaneously following dilution with water or aqueous media upon gentle agitation. The self-emulsification process is specific to the oil/surfactant ratio and surfactant concentration. The main goal of our study was to formulate SMES that are able to form microemulsions with water or aqueous media on wide area of (pseudo)ternary phase diagram. Various combinations of oils (castor oil, linseed oil and PeceolTM), surfactants (Labrasol®, Cremophor® EL and Tween® 20) and co-surfactants (Cremophor® RH 40, Solutol® HS-15 and CapryolTM 90) were studied in order to find optimal oil/surfactant ratio. (Pseudo)ternary phase diagrams were constructed from above mentioned components with titration technique and regions of microemulsions were determined based on organoleptic characteristics/properties and results of specific electrical conductivity. Combination of PeceolTM and castor or linseed oil as oil phase and Cremophor® EL as surfactant was confirmed to form the largest microemulsions area on (pseudo)ternary phase diagram, and the region was even wider after addition of co-surfactants into the system, especially after adding Cremophor® RH 40. Selected S(M)ES that formed the widest microemulsion area on (pseudo)ternary phase diagrams were based on results of droplet size after dilution classified as type III by Pouton; strictly speaking S(M)ES 1-6, 8 and 9 with droplets smaller than 100 nm as type IIIA (SMES) and S(M)ES 7 with droplets smaller than 250 nm as type IIIB (SES). Solubility and stability assessment of model substances NDS 1, NDS 2 and NDS 8 was performed in selected S(M)ES. According to the results S(M)ES 3, 5 and 8 were proven as possible delivery systems for model substance NDS 8, while solubility of model substances NDS 1 and NDS 2 was also very high, but the stability was not adequate.