Raziskava in vrednotenje vpliva formaldehida na fizikalno-kemijske lastnosti trdih želatinskih kapsul

Praunseis, Eva (avtor), Mravljak, Janez (mentor), Hren, Jure (komentor)

Želatina je zaradi pozitivnih mehanskih in tehnoloških lastnosti zelo pogosto uporabljen material v številnih farmacevtskih oblikah. Ena izmed glavnih slabosti uporabe želatine je njena reaktivnost zaradi katere pride do nastanka močnih kovalentnih vezi med amino skupinami na verigi peptidnega polimera. Produkt je premrežena želatina, ki ima spremenjene lastnosti. Premrežena želatina ima drugačno strukturo, višjo molekulsko maso in je manj hidrofilna. Farmacevtske oblike, ki vsebujejo želatino v zunanji plasti, kot so npr. trde in mehke želatinske kapsule in z želatino obložene tablete, so še posebej dovzetne za spremembo kakovosti, ki je posledica spremenjenih lastnosti želatine zaradi premreženja. V magistrski nalogi smo proučevali vpliv formaldehida na lastnosti trdih želatinskih kapsul. Trde želatinske kapsule smo v prvem delu magistrske naloge izpostavili atmosferi formaldehida pri povišani temperaturi za različne čase in tako dobili različno močno premrežene želatinske kapsule. Izvedli smo kontrolne poskuse, da smo izločili morebiten vpliv povišane temperature in topila. V drugem delu naloge smo trde želatinske kapsule polnili s pomožnimi snovmi, iz katerih formaldehid nastaja in situ ob njihovem razpadu. Kot pomožni snovi smo uporabili hidroksipropilmetil celulozo (HPMC) in polietilen glikol (PEG), ki smo jima z metodo HPLC določili vsebnost formaldehida. Na trdih želatinskih kapsulah smo izvedli gravimetrično analizo netopnega preostanka, teste sproščanja in jim posneli spektre FT-IR. Z gravimetričnim določanjem netopnega preostanka smo spremljali potek reakcije premreženja in ugotovili, da je hitrost reakcije premreženja odvisna od količine prisotnega formaldehida. Ugotovili smo, da se je masa netopnega preostanka z daljšanjem časa izpostavljenosti kapsul HCHO/DMSO oz. z večjim obsegom premreženja povečevala. Z analizo posnetih spektrov FT-IR nismo mogli ugotoviti signifikantnih razlik med spektri premreženih in nepremreženih kapsul. Po kemometrični obdelavi spektrov s programskim paketom za analizo PCA, smo ugotovili, da je prisotnost ene komponente z daljšanjem časa izpostavljenosti kapsul HCHO/DMSO padala. S testi sproščanja smo ugotovili, da so kapsule, ki so bile izpostavljene HCHO/DMSO, izkazovale spremenjene profile sproščanja. Dlje časa kot je bila kapsula izpostavljena HCHO/DMSO, bolj je bilo upočasnjeno sproščanje zdravilne učinkovine in bolj so se povišali koeficienti variacije. Tudi v kapsulah, ki smo jih polnili s HPMC in PEG, smo zaznali povečano maso netopnega preostanka in upočasnjeno sproščanje zdravilne učinkovine na testu sproščanja. Kot najboljša metoda za zaznavanje premreženja v trdih želatinskih kapsulah se je izkazal test sproščanja.

• Jezik: Slovenski jezik
• Ključne besede: trde želatinske kapsule, formaldehid, premreženje, FT-IR, gravimetrija, test sproščanja
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2019
• PID: 20.500.12556/RUL-112715
• Datum objave v RUL: 07.11.2019

PRAUNSEIS, Eva, 2019, Raziskava in vrednotenje vpliva formaldehida na fizikalno-kemijske lastnosti trdih želatinskih kapsul [na spletu]. Magistrsko delo. [Dostopano 3 maj 2025]. Pridobljeno s: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=slv&id=112715

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Research and evaluation of formaldehyde effect on the physicochemical characteristics of hard gelatin capsules

Izvleček

Gelatin is widely used material in many pharmaceutical formulations due to its many positive mechanical and technological properties. Use of gelatin is problematic because of its reactivity, which leads to formation of strong covalent bonds between amino groups on the polymer chain and results in a cross-linked polymer with altered characteristics. Molecule of cross-linked gelatin has changed structure, is less hydrofillic and has higher molecular mass. Dosage forms, which contain gelatin in the outer layer, for example hard an soft gelatin capsules and gelatin coated tablets, are especially proned to change of quality due to altered characteristics of cross-linked gelatin. In this master’s degree we were researching and evaluating effect of formaldehyde on the characteristics of hard gelatin capsules. In the first part of research work hard gelatin capsules were exposed to formaldehyde atmosphere at elevated temperature for different time periods. As a result we got different extent of cross-linked gelatin capsules. In order to exclude possible effects of elevated temperature and presence of the solvent on the results we have performed control experiments. In the second part of research work hard gelatin capsules were filled with excipients, which during degradation process produce formaldehyde in situ. We used excipients hydroxypropyl methylcellulose (HPMC) and polyethylene glycol (PEG). Content of formaldehyde in excipients was experimentally determined by HPLC method. On stressed hard gelatin capsules we performed gravimetric determination of insoluble residue, dissolution tests and recorded their FT-IR spectra. We have followed kinetics of crosslinking reaction by gravimetric determination of insoluble residue from which we found the rate of reaction is determined by concentration of formaldehyde. We observed an increase in mass of insoluble residue when capsules were exposed to formaldehyde for longer time periods of time. By analyzing FT-IR spectra we could not distinguish between specters of cross-linked and uncross-linked capsules. After chemometric treatment of the specters with PCA software, we observed that with longer exposure of the capsules to formaldehyde one of the principal components was diminishing. During dissolution testing formaldehyde stressed capsules showed changed dissolution profiles. Capsules, which were exposed to formaldehyde atmosphere for longer time periods, showed slower drug release and had higher coefficient of variation. In comparison to unstressed capsules, capsules filled with HPMC and PEG had higher mass of insoluble residue and slowed down drug release at dissolution testing. Practice showed that the best method for detection of cross-linking in hard gelatin capsules is dissolution test.

• Ključne besede: hard gelatin capsules, formaldehyde, cross-linking, FT-IR, gravimetric analysis, dissolution test