Razvoj kalibracijskih modela za aktivne farmaceutske tvari

master's thesis

• Title (english): Development of calibration model for active pharmaceutical ingredients
• Author: Tesa Herceg
• Mentor: Željka Ujević Andrijić (mentor)
• Committee member: Željka Ujević Andrijić (predsjednik povjerenstva)
• Committee member: Nenad Bolf (član povjerenstva)
• Committee member: Jasna Prlić Kardum (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2023-01-27, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering

Abstract

Proces kristalizacije vrlo je važan proces u farmaceutskoj industriji. Njegova složenost i ovisnost o mnogim čimbenicima, kao i strogi zahtjevi za visokom kvalitetom i čistoćom farmaceutskih aktivnih tvari, stvorili su potrebu za razvojem naprednih instrumenata i tehnologija za kontinuirano praćenje i vođenje procesa. Procesna analitička tehnologija (PAT) sve se više primjenjuje u procesu kristalizacije za kontinuirano praćenje neke od ključnih značajki kvalitete proizvoda. PAT- tehnologija podrazumijeva kontinuirano praćenje koncentracije naprednim analitičkim instrumentima kao što su optičke sonde te razvoj i primjenu kalibracijskoga modela koji povezuje izmjerene spektralne podatke s koncentracijom farmaceutske aktivne tvari. Kalibracijski model moguće je razviti nekom od metoda strojnoga učenja. Cilj ovog rada je razviti i ispitati modele neuronskih mreža za modeliranje ovisnosti koncentracije farmaceutske aktivne tvari, ksilometazolin hidroklorida, u n-butanolu, o temperaturi i spektralnim podacima dobivenih mjerenjima ATR-FTIR spektrometrom. U radu je provedena predobrada spektralnih podataka, analiziran je broj neurona u prvom i drugom skrivenom sloju, broj skrivenih slojeva, vrsta primijenjenoga algoritma učenja te utjecaj vrste prijenosne funkcije na kvalitetu razvijenih neuronskih mreža.

Abstract (english)

The crystallization process is a very important process in the pharmaceutical industry. The complexity of the crystallization process and the dependence of this process on many factors, as well as the strict requirements for high quality and purity of active pharmaceutical ingredients, have led to the need to develop advanced instruments and technologies for continuous monitoring and process control. Process analytical technology (PAT) is increasingly being applied in the crystallization process to continuously monitor some of the key product quality characteristics. The PAT technology involves continuous monitoring of the concentration with advanced analytical instruments such as optical probes and the development of a calibration model that relates the measured spectral data to the concentration of the pharmaceutically active substance. The calibration model can be developed using machine learning methods. The aim of this work was to develop and investigate neural network models for modeling the dependence of the concentration of the active pharmaceutical ingredient, xylometazoline hydrochloride in n-buthanol on temperature and spectral data obtained by ATR-FTIR spectrometer measurements. The effects of the preprocessing of the spectral data, the number of neurons in the first and second hidden layers, the number of hidden layers, and the type of optimizer and transfer function used on the quality of the evolved neural networks were analyzed.

• Keywords: kristalizacija; procesna analitička tehnologija; ATR-FTIR spektrometrija; strojno učenje; ksilometazolin
• Keywords (english): crystallization; process analytical technology; ATR-FTIR spectrometry; machine learning; xylometazoline
• Language: croatian
• URN:NBN: urn:nbn:hr:149:646971
• Project: Number: KK.01.1.1.07.0017; Title: Napredno vođenje procesa kristalizacije; Title: Advanced Control of Crystallization Process; Acronym: CrystAPC; Leader: Nenad Bolf; Jurisdiction: Croatia; Funder: EK; Funding stream: EFRR
• Study programme: Title: Chemical Engineering - Graduate study; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka kemijskog inženjerstva (magistar/magistra inženjer/inženjerka kemijskog inženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2023-03-01
• Created on: 2023-02-15 12:57:21