Vrednotenje vpliva premreževalnih ionov na lastnosti alginatnih mikrosfer

Erjavec, Špela (avtor), Zvonar Pobirk, Alenka (mentor), Gosenca Matjaž, Mirjam (komentor)

Alginatne mikrosfere spadajo med novejše dostavne sisteme, ki omogočajo tako nadzorovano sproščanje vgrajenih zdravilnih učinkovin in njihovo zaščito pred dejavniki okolja kot tudi prekrivanje njihovega vonja in okusa. Gre za ogrodni tip mikrokapsul, pri katerem sta mikrokapsulirana snov in ogrodni material enakomerno razporejena po celotnem volumnu delca. Pripravimo jih lahko z različnimi kemijskimi, fizikalno-kemijskimi ter fizikalno-mehanskimi metodami. Na uspešnost mikrokapsuliranja ima velik vpliv tudi izbira ustreznega ogrodja, pri čemer je v farmacevtski industriji še vedno v ospredju uporaba naravnih polimerov, kot sta natrijev alginat in hitosan. V magistrski nalogi smo proučevali vpliv premreževalnih ionov na lastnosti alginatnih mikrosfer. Za izdelavo slednjih smo uporabili metodo z vibrirajočo membrano, ki sodi med fizikalno-mehanske postopke mikrokapsuliranja. Temelji na ekstruziji laminarnega curka tekočine skozi šobo enkapsulatorja, nad katero se nahaja membrana, ki z vibriranjem povzroči razbitje laminarnega toka v enakomerno velike kapljice. Le-te med padanjem proti premreževalni raztopini potujejo skozi električno polje, pri čemer se njihova površina nabije, kar preprečuje njihovo zlepljanje. Za premreževanje mikrosfer smo uporabili različne premreževalne raztopine in sicer 0,3 M in 0,5 M raztopino CaCl2, 0,3 M CuCl2, 0,3 M AlCl3, 0,3 M CaCl2/ZnCl2 ter 0,3 M CaCl2 + 1% raztopino hitosana. Njihov vpliv na lastnosti izdelanih mikrosfer smo proučevali z vrednotenjem nabrekanja in erozije alginatnih mikrosfer ter sproščanje vgrajene dobro topne modelne učinkovine pentoksifilina v mediju s pH = 3, prečiščeni vodi in fosfatnem pufru s pH = 6,8, pri čemer se je slednji izkazal kot najbolj diskriminatoren medij, kar pomeni, da so se v tem mediju najbolj izrazile razlike med premreževalnimi ioni. V vseh medijih se je iz alginatnih mikrosfer sprostila vsa vgrajena zdravilna učinkovina, vpliv različno premreženega gelskega ogrodja pa je bil najbolje viden v fosfatnem pufru s pH = 6,8, v katerem je pentoksifilin tudi slabše topen. Največji delež (94 %) vgrajenega pentoksifilina se je tako po prvi uri sprostil iz mikrosfer premreženih z 0,5 M CaCl2, najmanjši delež (81 %) pa se je v tem času sprostil iz mikrosfer premreženih z 0,3 M raztopino CaCl2, ki so bile obdane z dodatno hitosansko ovojnico. Vpliv premreževalnih ionov na lastnosti izdelanih mikrosfer smo spremljali tudi z vrednotenjem mehanskih lastnosti gelskega ogrodja. Z vrednotenjem teksture smo ugotovili, da imajo najbolj čvrsto ogrodje mikrosfere, ki smo jih premrežili z 0,3 M raztopino CuCl2, najmanjšo čvrstost pa izkazujejo mikrosfere, premrežene z 0,3 M raztopino CaCl2 z dodatno hitosansko ovojnico. Vgradnja zdravilne učinkovine sicer ni vplivala na čvrstost alginatnih mikrosfer. Zaradi dobre vodotopnosti zdravilne učinkovine pentoksifilina je bil manj viden vpliv premreževalnih ionov na sproščanje vgrajene učinkovine kot v primeru slabo vodotopnega furosemida, uporabljenega v predhodnem raziskovalnem delu na Katedri za farmacevtsko tehnologijo. Kljub temu so alginatne mikrosfere obetaven dostavni sistem za dostavo zdravilnih učinkovin, zlasti tistih s slabšimi biofarmacevtskimi lastnostmi.

• Jezik: Slovenski jezik
• Ključne besede: alginatne mikrosfere, premreževalni ioni, analiza teksture, pentoksifilin, sproščanje
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2021
• PID: 20.500.12556/RUL-128126
• Datum objave v RUL: 03.07.2021

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Influence Evaluation of cross-linking ions influence on characteristics of alginate microspheres

Izvleček

Alginate microspheres are novel drug delivery systems used not only for controlled release of incorporated drugs and their protection from environment but also for masking their smell and taste. They are defined as microspheres with encapsulated substance evenly dispersed within the polymeric matrix. Microspheres can be prepared with different chemical, physico-chemical and physico-mechanical methods. Successful production depends on selection of the right matrix polymer, with natural polymers as sodium alginate and chitosan predominantly used in pharmaceutical industry. The aim of the thesis was to evaluate the influence of cross-linking ions on characteristics of alginate microspheres produced by vibrating nozzle technique. This method is based on extrusion of the lamellar liquid jet through the nozzle of the encapsulator, where it is broken into uniformly sized droplets by vibrations produced by the membrane positioned above the nozzle. Between the nozzle and the cross-linking solution formed droplets pass through an electric field creating charge on the surface of unhardened microspheres, which prevents them from sticking together. Cross-linking solutions used for hardening the microspheres were the following: 0.3 M and 0.5 M CaCl2, 0.3 M CuCl2, 0.3 M AlCl3, 0.3 M CaCl2/ZnCl2 and 0.3 M CaCl2 + 1% chitosan solution. In order to evaluate their influence on characteristics of crosslinked matrix, the swelling, erosion and drug release studies were performed of alginate microspheres in purified water and mediums with pH = 3 and phosphate buffer with pH = 6,8 as the most discriminatory medium. Complete release of freely water-soluble model drug pentoxifylline was observed in all mediums, with most pronounced differences between differently crosslinked matrices observed in phosphate buffer with pH = 6,8 with lowest pentoxifylline solubility. In the first hour the highest percentage of pentoxifylline was released from microspheres cross-linked with 0.5 M CaCl2 solution, while additional chitosan coating contributed to the lowest amount of released drug from the microspheres cross-linked with 0.3 M CaCl2. The influence of cross-linking ions on characteristics of microspheres was also studied by evaluation of their mechanical properties. Their hardness characteristics were obtained from texture analysis performed with rheometer. Results showed that microspheres cross-linked with 0.3 M CuCl2 solution expressed the greatest hardness and they also showed the lowest swelling degree, while the lowest hardness was determined for microspheres cross-linked with 0.3 M CaCl2 solution with additional chitosan coating. Encapsulated drug did not influence the hardness of alginate microspheres. Due to good aqueous solubility of pentoxifylline the dependence of drug -release on cross-linking ions used for hardening the alginate microspheres is less pronounced as compared to poorly water-soluble drug furosemide, used in previous experimental work in Department for pharmaceutical technology. Nevertheless, alginate microspheres are promising drug delivery system, especially for drugs with poor biopharmaceutical properties.

• Ključne besede: alginate microspheres, cross-linking ions, texture analysis, pentoxifylline, dissolution test