Vpliv vrste polnila, veziva, razgrajevala in deleža iztiskanca na stisljivost zmesi ter trdnost in razpadnost izdelanih tablet

Poje Vampelj, Maruša (author), German Ilić, Ilija (mentor), Jakasanovski, Ognen (comentor)

Trdne disperzije so disperzije zdravilnih učinkovin v trdnem, inertnem nosilcu, ki jih lahko izdelamo z različnimi metodami, najpogosteje z metodo iztiskanja talin in sušenja z razprševanjem. Prednosti trdnih disperzij so povečana hitrost raztapljanja slabo vodotopnih zdravilnih učinkovin (BCS razred II, IV), kar običajno vodi v njihovo višjo biološko uporabnost. Zaradi slabih pretočnih lastnosti zmesi in slabše stisljivosti je proces tabletiranja trdnih disperzij lahko izziv, vendar se z dodajanjem pomožnih snovi lastnosti zmesi za tabletiranje izboljšajo. Cilj magistrske naloge je bil ugotoviti, kako različne vrste polnil, superrazgrajeval in delež placebo iztiskanca vplivajo na pretočnost in stisljivost zmesi za tabletiranje ter na trdnost in razpadnost nastalih tablet. V okviru eksperimentalnega dela smo preverjali vpliv polnil mikrokristalne celuloze (MCC), dikalcijevega fosfata in laktoze, ter superrazgrajeval Na-karamelozata (Na-CMC), krospovidona in Na škrobnega glikolata na lastnosti tablet, ki so bile sestavljene iz placebo iztiskanca sestavljenega iz polimera kopovidon. Preverjali smo vpliv več t.i. vhodnih spremenljivk, delež placebo iztiskanca, vrste polnila in superrazgrajevala, pri tem pa smo uporabili tudi načrt eksperimentov (angl. Design of experiments, DoE). Ugotovili smo, da na pretočnost, kompresibilnost, tabletabilnost ter razpadnost tablet močno vpliva delež placebo iztiskanca, vrsta polnila in superrazgrajevala. Najboljše pretočne lastnosti so imele zmesi s 25% deležem placebo iztiskanca in polnilom dikalcijev fosfat ter superrazgrajevalom Na-CMC. Zmesi s 25% deležem placebo iztiskanca in polnilom MCC so imele najboljšo kompresibilnost in tabletabilnost, ki sta se z večanjem placebo iztiskanca precej zmanjšali. Zmes s polnilom MCC pa je imela tudi večji indeks elastične relaksacije kot zmes s polnilom dikalcijev fosfat. Pri vrednotenju razpadnosti so imele najkrajši čas zmesi s 25% deležem placebo iztiskanca in polniloma MCC ali dikalcijev fosfat. Pri povečanem deležu placebo iztiskanca se je razpadnost tablet močno podaljšala. Iz rezultatov smo lahko ocenili najustreznejšo sestavo tablete glede na posamezne želene lastnosti. Kot najustreznejšo sestavo bi za izdelavo prototipa lahko uporabili zmes s 25% deležem placebo iztiskanca, polnilom MCC ali dikalcijev fosfat in superrazgrajevalom Na-CMC.

• Language: Slovenian
• Keywords: trdna disperzija, stisljivost, tabletabilnost, pretočnost, delež placebo iztiskanca, eksperimentalni načrt
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2024
• PID: 20.500.12556/RUL-164714
• Publication date in RUL: 08.11.2024

Secondary language

• Language: English
• Title: The influence of filler, binder, disintegrant type and extrudate ratio on the compaction of mixture and on hardness and disintegration time of produced tablets

Abstract

Solid dispersions are dispersions of active pharmaceutical ingredients in a solid, inert carrier, typically produced through methods such as hot-melt extrusion and spray drying. The advantages of solid dispersions include an increased dissolution rate of poorly water-soluble drugs (BCS class II, IV), which enhances their bioavailability. Due to poor flow properties of the mixtures and reduced compressibility, the tableting process can be challenging, but the addition of excipients improves the properties of the mixture for tableting. The aim of this thesis was to determine how different types of fillers, superdisintegrants, and the proportion of placebo extrudate affect the flowability and compressibility of the mixtures for tableting, as well as the hardness and disintegration time of the resulting tablets. We examined the impact of the fillers such as microcrystalline cellulose (MCC), dicalcium phosphate, and lactose, as well superdisintegrants such as Na-carmellose (Na-CMC), crospovidone, and sodium starch glycolate on the properties of tablets composed of a placebo copovidone extrudate. We examined the influence of several input variables, including the proportion of placebo extrudate, the type of filler, and the type of superdisintegrant, using the Design of Experiments (DoE) approach. The results showed that flowability, compressibility, tabletability, and disintegration of the tablets were significantly influenced by the proportion of placebo extrudate, the type of filler, and the type of superdisintegrant. The best flow properties were observed in mixtures with a 25% proportion of placebo extrudate, dicalcium phosphate as the filler, and Na-CMC as the superdisintegrant. Mixtures with 25% placebo extrudate and MCC as the filler exhibited the best compressibility and tabletability, both of which significantly decreased with an increased proportion of placebo extrudate. The mixture with MCC also showed a higher elastic relaxation index compared to the mixture with dicalcium phosphate. In terms of disintegration time, the shortest times were observed in mixtures with a 25% placebo extrudate content and MCC or dicalcium phosphate as the filler. With an increased proportion of placebo extrudate, tablet disintegration time was significantly prolonged. Based on the results, we were able to evaluate the most appropriate tablet composition for the desired properties. For prototype development, the most suitable composition would be a mixture with 25% placebo extrudate, MCC or dicalcium phosphate as the filler, and Na-CMC as the superdisintegrant.

• Keywords: solid dispersion, compressibility, tabletability, flowability, proportion of placebo extrudate, design of experiments