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Uporaba procesno analiznih tehnik pri spremljanju izdelave trdnih disperzij amlodipinijevega maleata
ID Medved, Laura (Author), ID Vrečer, Franc (Mentor) More about this mentor... This link opens in a new window, ID Korasa, Klemen (Comentor)

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Abstract
Slaba topnost zdravilnih učinkovin predstavlja pomemben izziv farmacevtske industrije pri razvoju novih originatorskih in generičnih zdravil. Kot način za izboljšanje biološke uporabnosti slabo topnih učinkovin se vse pogosteje uporabljajo trdne disperzije, ki so definirane kot disperzije ene ali več zdravilnih učinkovin v inertnem nosilcu v trdnem agregatnem stanju. Pripravimo jih s širokim spektrom metod, med katerimi se najpogosteje uporabljajo metode z uporabo topil. Med slednje spada tudi vrtinčnoslojno granuliranje, ki smo ga izvedli pri našem raziskovalnem delu. Med procesom smo razprševali raztopino učinkovine in polimera na delce inertnega nosilca, pri čemer je prišlo do nastanka zrnc. Proces izdelave amorfne trdne disperzije smo spremljali in vrednotili ob proizvodni liniji z ramansko spektroskopijo ter v laboratoriju izvedli dodatne analize z bližnjo infrardečo spektroskopijo. Omenjeni tehniki sta najpogosteje uporabljeni procesno analizni tehnologiji za spremljanje farmacevtskih proizvodnih procesov. Iz spektroskopskih podatkov, pridobljenih s procesno analiznimi analizatorji, smo s pomočjo multivariatne analize in metode delnih najmanjših kvadratov izdelali modele za napoved vsebnosti in deleža kristalinične učinkovine v vzorcih granulata. Vrednosti, napovedane z modeli, smo primerjali z dejanskimi vrednostmi, določenimi z referenčno metodo. Dodatno smo z metodo glavnih komponent preverili primerljivost poskusov. Izdelane modele smo eksperimentalno ovrednotili in pri vseh ugotovili sprejemljivo napako pri napovedovanju in dobro ujemanje napovedanih vrednosti z dejanskimi. S tem smo pokazali, da lahko s pomočjo bližnjih infrardečih in ramanskih spektroskopskih meritev izdelamo modele, ki jih lahko uporabimo pri procesih izdelave trdnih disperzij za spremljanje vsebnosti in detektiranje morebitnega pojava kristalinične oblike učinkovine.

Language:Slovenian
Keywords:amorfne trdne disperzije, vrtinčnoslojno granuliranje, procesno analizna tehnologija, multivariatna analiza podatkov
Work type:Master's thesis/paper
Organization:FFA - Faculty of Pharmacy
Year:2024
PID:20.500.12556/RUL-156253 This link opens in a new window
Publication date in RUL:16.05.2024
Views:96
Downloads:456
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Secondary language

Language:English
Title:Application of process analytical tools in monitoring the production of amlodipine maleate solid dispersions
Abstract:
Poor solubility of active pharmaceutical ingredients represents an important challenge for pharmaceutical industry in the development of new original and generic drugs. As a way to improve bioavailability of poorly water-soluble active ingredients, solid dispersions are increasingly being utilized. They are defined as dispersions of one or more active ingredients in an inert carrier in a solid state and can be prepared using a wide variety of methods, with solvent-based methods being most commonly employed. This group of methods also include fluidized bed granulation, which was used in our research work. During the process, we sprayed a solution of the active ingredient and polymer onto inert carrier particles, resulting in the formation of granules. We monitored the process along the production line using Raman spectroscopy and performed further analyses in the laboratory using near infrared spectroscopy. Both techniques are most commonly used process analytical technologies for monitoring pharmaceutical manufacturing processes. Using spectroscopic data from the process analytical technology analysers, we employed multivariate analysis and partial least squares regression to create models for predicting the content and proportion of crystalline active ingredient in granulate samples. We compared the values predicted by the models with the actual values, determined by reference methods. In addition, we verified the comparability of the experiments using the principal component analysis method. We experimentally evaluated the developed models and found acceptable prediction errors and a good fit between the predicted and actual values in all of them. This demonstrated that based on near infrared and Raman spectroscopic measurements, we can create models that can be used in the solid dispersion production processes for monitoring the content of pharmaceutical active ingredient and detecting the potential occurrence of its crystalline forms.

Keywords:amorphous solid dispersions, fluid-bed granulation, process analytical technology, multivariate data analysis

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