Vrednotenje tehnološkega postopka izdelave gela za oko na osnovi polikarbofila in hidroksipropilmetilceluloze

Janežič, Urška (author), Kocbek, Petra (mentor), Šuklje Debeljak, Helena (comentor)

Največja prednost gelov za oko v primerjavi z ostalimi farmacevtskimi oblikami za oko je daljši časa zadrževanja na mestu aplikacije zaradi večje viskoznosti. Tvorilci gela so različni polimeri ali njihove kombinacije. Hidroksipropilmetilceluloza je derivat celuloze, ki ima sposobnost termoreverzibilnega geliranja, njena topnost v vodi pa z naraščanjem temperature pada. Polikarbofil je poliakrilatni polimer, ki v vodi tvori kisle disperzije in nabreka, po zvišanju pH disperznega medija pa tvori hidrogel. V okviru magistrske naloge smo vrednotili tehnološki postopek izdelave hidrofilnega gela za oko na osnovi kombinacije hidroksipropilmetilceluloze in polikarbofila. Naredili smo vzorce gela, tako da smo spreminjali tehnološke parametre izdelave gela ter v nekaterih primerih tudi sestavo formulacije. Vsem končnim gelom smo vrednotili reološke lastnosti, in sicer smo izvedli rotacijski test meritve viskoznosti pri konstantni strižni hitrosti, rotacijski test logaritemskega naraščanja strižne hitrosti ter oscilacijski amplitudni test. Obnašanje formulacij med samo pripravo vzorcev gela smo spremljali in vrednotili tudi vizualno. Dobro dispergiranje polimerov v disperznem mediju se je izkazalo kot pomemben korak v postopku priprave gela, saj je le-to predpogoj za ustrezno funkcionalnost polimerov v formulaciji in nastanka homogenega gela z ustreznimi reološkimi lastnostmi. Med pripravo gela je zaradi nagnjenosti disperzije k penjenju potrebno postopek izdelave prilagoditi tako, da penjenje minimiziramo. Kot bistvene parametre, ki vplivajo na reološke lastnosti gela, smo prepoznali vsebnost polimerov, pH končnega gela in avtoklaviranje zmesi disperzij polimerov, predvsem zaradi temperaturno odvisnega obnašanja vodne disperzije hidroksipropilmetilceluloze. Ugotovili smo, da je za elastično obnašanje viskoelastičnega gela odgovoren predvsem polikarbofil, medtem ko ima hidroksipropilmetilceluloza opazen vpliv le na plastične lastnosti gela. Zaznali smo tudi časovni vpliv staranja gela na reološke lastnosti gela. Vpliv ostalih tehnoloških parametrov je bil opazen, a manj izrazit. Ker sta bila kot zgoščevali v formulaciji prisotna dva polimera z različnimi lastnostmi, je bilo vrednotenje vpliva tehnološkega postopka izdelave gela na reološke lastnosti gela dodatno zapleteno zaradi morebitnih medsebojnih vplivov in interakcij polimerov.

• Language: Slovenian
• Keywords: gel za oko, hidroksipropilmetilceluloza, polikarbofil, reologija
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2023
• PID: 20.500.12556/RUL-152289
• Publication date in RUL: 17.11.2023

Secondary language

• Language: English
• Title: Evaluation of technological procedure for production of an eye gel based on polycarbophil and hydroxypropylmethylcellulose

Abstract

The greatest advantage of eye gels compared to other ophthalmic drug dosage forms is the longer retention time at the application site due to their higher viscosity. The gel formers are different polymers or their combinations. Hydroxypropylmethylcellulose is a cellulose derivative which has reversible thermogel properties and its solubility in water decreases with increasing temperature. Polycarbophil is a polyacrylate polymer which forms acid dispersions and swells in water. It forms a hydrogel when the pH of the dispersion medium is increased. In this master thesis we evaluated the technological procedure for production of a hydrophilic eye gel based on a combination of hydroxypropylmethylcellulose and polycarbophil. Gel samples were produced by varying the technological parameters of the gel production and, in some cases, also the composition of the formulation. The rheological properties of all final gels were evaluated by performing a rotational test of viscosity measurement at constant rotation rate, a rotational test with logarithmic increase in shear rate and an oscillatory amplitude sweep. Behaviour of the formulations during the gel samples preparation itself was also monitored and evaluated visually. Good dispersion of the polymers in the dispersion medium proved to be an important step in the gel preparation process, as it is a prerequisite for adequate functionality of the polymers and to obtain a homogeneous gel with appropriate rheological properties. During gel preparation, the foaming tendency of the dispersion requires adjustments of the production process, to minimise foaming. As essential parameters affecting the rheological properties of the gel, we identified the polymer concentration, pH of the final gel and autoclaving of the polymer dispersion blend, mainly due to the temperature-dependent behaviour of the aqueous dispersion of hydroxypropylmethylcellulose. We found that polycarbophil is mainly responsible for the elastic behaviour of the viscoelastic gel, while hydroxypropylmethylcellulose has a notable influence only on the plastic properties of the gel. We also detected the temporal effect of gel ageing on the rheological properties of the gel. The influence of other technological parameters was noticeable but less pronounced. Since two polymers with different properties were present as thickeners in the formulation, the evaluation of the influence of the gel production process on the rheological properties of the gel was further complicated by the potential interactions of the polymers.

• Keywords: eye gel, hydroxypropylmethylcellulose, polycarbophil, rheology