Proizvodnja farmaceutskih peleta

master's thesis

• Title (english): The manufacturing of pharmaceutical pellets
• Author: Mateja Štanfel
• Mentor: Gordana Matijašić (mentor)
• Committee member: Gordana Matijašić (predsjednik povjerenstva)
• Committee member: Krunoslav Žižek (član povjerenstva)
• Committee member: Vesna Tomašić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2019-09-27, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering

Abstract

Ideja za ovim istraživanjem potaknuta je razvojem novih sustava za dostavu lijeka. Većina djelatnih tvari odmah se oslobađa iz lijeka te je njihovo djelovanje trenutno, zbog toga se nastoji pronaći formulacija koja će kontrolirano oslobađati djelatnu tvar i na taj način djelovati u tijelu kroz duži vremenski period. Nakon priprave lijeka, bitno je da je lijek stabilan i da oslobađa djelatnu tvar u točno određenom dijelu gastrointestinalnog trakta. U ovom radu istraživanje je provedeno u nekoliko koraka, a to je priprava peleta pomoću dvije različite metode. Impregnirane pelete pripremljene su miješanjem mikrokristalne celuloze i natrijeva klorida u masenom omjeru 70:30 te ekstrudiranjem i sferoniziranjem, a potom ispiranjem destiliranom vodom do porozne strukture. Dronedaron-hidroklorid (DNR) kao djelatna tvar u obliku nanosuspenzije, vakuumski je impregniran u pore peleta. Pelete označene kao 100 mg i 400 mg pripremljene su direktnim ugrađivanjem dronedaron-hidroklorida u pelete mikrokristalne celuloze tijekom ekstrudiranja, a potom su sferonizirane. Peletama je određena specifična površina, raspodjela veličina pora, raspodjela veličina čestica i morfologija te je određen sadržaj djelatne tvari. Ispitana je brzina oslobađanja dronedarona iz peleta metodom in vitro. Dobiveni profili oslobađanja opisani su modelom procesa prvoga reda. Rezultati su pokazali da je metoda direktnim ugrađivanjem DNR u pelete djelotvornija metoda nanošenja djelatne tvari u odnosu na vakuumsku impregnaciju jer daje mogućnost postizanja većih doza lijeka. Kinetika oslobađanja DNR iz peleta opisana je modelom prvog reda, a konstanta brzine oslobađanja potvrdila je najsporije oslobađanje DNR iz 100 mg peleta. Oblaganjem peleta dodatno je usporeno oslobađanje djelatne tvari. Profili oslobađanja DNR iz peleta 400 mg 60c najbliži su profilima oslobađanja Multaq tablete, a dodatne modifikacije mogu se postići oblaganjem. Ovim istraživanjem pokazano je da je različitom pripravom peleta te nanošenjem djelatne tvari i obloge moguće postići bolju kontrolu oslobađanja. Mogu se pripremiti dozirni oblici različitih sadržaja djelatne tvari i iskoristiti višestruke prednosti peleta u odnosu na tablete kao dozirni oblik.

Abstract (english)

The idea behind this research was inspired by the development of new drug delivery systems. Most of the active substances are released from the drug immediately and their action is immediate, therefore, an effort is made to find a formulation that will release the active substance in a controlled way over a long period. After the preparation of the drug, it is important that the drug is stable and releases the active substance in a specific part of the gastrointestinal tract. In this paper, the research was carried out in several steps, which is the preparation of pellets using two different methods. The impregnated pellets were prepared by mixing microcrystalline cellulose and sodium chloride in a mass ratio of 70:30, extruding the mixture, spheronizing and then washing to remove NaCl to achieve a porous structure of pellets. Dronedarone hydrochloride (DNR), in form of nanosuspension, is vacuum-impregnated into the pellet pores. Pellets marked as 100 mg and 400 mg were prepared by direct incorporation of dronedarone hydrochloride into microcrystalline cellulose pellets during extrusion, and then spheronized. The specific surface area, pore size distribution, particle size distribution and morphology of pellets were examined and the content of active substance was determined. The release rate of dronedarone from the pellets was investigated by in vitro method. A first-order model describes the resulting release profiles. The results showed that the method of direct incorporation of DNR into pellets is a more effective method of application of the active substance over vacuum impregnation because it gives the possibility of obtaining higher doses of the drug. A first-order model described the kinetics of DNR release, and the release rate constant confirmed the slowest DNR release from 100 mg pellets. The coating of the pellets furthermore slows down the release of the active substance. The DNR release profiles of 400 mg 60c pellets are closest to the release profiles of the Multaq tablet, and additional modifications can be achieved by coating. This study showed that different pellet preparation and application of DNR and coating material could achieve better release control. Dosage forms of various active substance contents can be prepared and the multiple advantages of pellets over tablets as a dosage form can be utilized.

• Keywords: dronedaron-hidroklorid; pelete; kontrolirano oslobađanje; kinetika oslobađanja
• Keywords (english): dronedaron hydrochloride; pellets; controlled release; kinetics profiles
• Language: croatian
• URN:NBN: urn:nbn:hr:149:892986
• Study programme: Title: Environmental Engineering - Graduate study; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka ekoinženjerstva (magistar/magistra inženjer/inženjerka ekoinženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-02-27 16:14:36