Preučevanje vpliva različnih dejavnikov na določitev vodne aktivnosti v farmacevtskih oblikah

Ličen, Anže (author), Roškar, Robert (mentor), Trdan Lušin, Tina (comentor)

Količino vode v farmacevtskih oblikah določamo na različne načine. Ena od tehnik je vodna aktivnost (aw), ki podaja količino proste vode v farmacevtski obliki. Prosta voda je na razpolago za kemijske, fizikalne interakcije in za zagotavljanje pogojev okolja za mikrobiološko rast. Po definiciji je aw razmerje med parnim tlakom vode nad vzorcem in parnim tlakom čiste vode pri enaki temperaturi. Za merjenje aw se uporabljajo različni tipi merilcev, ki delujejo na različnih principih merjenja. V magistrski nalogi smo preverili, kako različni dejavniki vplivajo na določitev aw farmacevtskih oblik. V ta namen smo najprej razvili in validirali metode merjenja aw za štiri izbrane farmacevtske oblike (praškasta zmes, trde želatinaste kapsule, HPMC kapsule, tablete). Preverili smo, kako dobro lahko s teoretičnimi izračuni iz sorpcijskih izoterm posameznih pomožnih snovi in masnih deležev napovemo sorpcijske izoterme farmacevtskih oblik. S primerjavo teoretičnih in eksperimentalnih podatkov vsebnosti vode v odvisnosti od aw smo ugotovili zelo dobro ujemanje v primeru testiranih farmacevtskih oblik. V tem sklopu smo tudi preverili vpliv tehnološkega procesa na sorpcijsko izotermo. S primerjavo sorpcijskih izoterm praškaste zmesi in tablet enake kvalitativne in kvantitativne sestave smo ugotovili, da tabletiranje testirane sestave ne vpliva na sorpcijsko izotermo. V nadaljevanju smo na vzorcu želatinastih kapsul potrdili, da teorija o enakosti aw vseh komponent farmacevtske oblike v ravnotežju drži. Ovrednotili smo tudi vpliv hlapnih organskih topil na določitev aw, ki lahko po izdelavi zaostanejo v končnem izdelku. Različno navlaženim vzorcem smo dodali hlapna organska topila (etanol, izopropanol, aceton) in spremljali vpliv topil na določitev aw. Ugotovili smo, da zaostanek topil na nivoju dovoljene meje skladno s smernico ICH Q3C vpliva na določitev aw vzorca. Nazadnje smo preverjali še vpliv relativne vlažnosti prostora, v katerem smo izvajali meritve na določitev aw. Ugotovili smo, da je meritve smiselno izvajati pri relativni vlažnosti, ki je čim bolj primerljiva z aw merjenega vzorca. Meritve smo izvajali na dveh merilcih (AquaLab, LabMaster), ki imata različen princip merjena vodne aktivnosti. Merilec AquaLab meri vodno aktivnost na principu temperature rosišča s hlajenim zrcalom, merilec LabMaster pa na principu spremembe rezistence elektrolita. Na osnovi pridobljenih rezultatov lahko zaključim, da merilca podajata primerljive rezultate, pri obeh pa je bilo zaznano, da zaostanki topil v izdelkih lahko motijo meritev aw.

• Language: Slovenian
• Keywords: Vodna aktivnost, farmacevtske oblike, sorpcijska izoterma, organska topila, vpliv relativne vlažnosti.
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2021
• PID: 20.500.12556/RUL-126356
• Publication date in RUL: 18.04.2021

Secondary language

• Language: English
• Title: A study of various factors influencing determination of water activity in pharmaceutical dosage forms

Abstract

The amount of water in pharmaceutical dosage forms (PDF) is determined by different experimental techniques. One of them is water activity (aw) measurement, which gives information about the amount of free water in PDF. Free water is available for chemical changes, physical interactions and for microbiological growth. By definition, aw is the ratio between the vapor pressure of water above the sample and the vapor pressure of pure water at the same temperature. Different types of devices are used to measure aw, which operate on different measurement principles. In the master's thesis we examined how different factors influence the determination of aw in PDF. For this purpose, we first developed and validated aw measurement methods for four selected PDF (powder mixture, hard gelatin capsules, HPMC capsules, tablets). Then we compared the obtained sorption isotherms of PDF to the theoretical calculations from the sorption isotherms of individual excipients and mass fractions. We found very good agreement between experimental data and theoretical prediction for all four tested PDF. In this section, we also examined the influence of the technological process on the sorption isotherm. By comparing the sorption isotherms of the powder mixture and tablets containing the same qualitative and quantitative composition, we showed that the tableting does not affect the sorption isotherm. Next, by examining the sample of gelatin capsules, we confirmed the theoretical equality of aw for all the components of the PDF in equilibrium. We also evaluated the influence of volatile organic solvents (ethanol, isopropanol, acetone) on the determination of aw, which were added to variously moistened samples. We found that the residual solvents at the level of the permissible limit in accordance with the ICH Q3C guideline affect the determination of the aw. Finally, we checked the influence of the relative humidity of the room in which we performed the measurements of aw. We concluded that it makes sense to perform measurements at a relative humidity that is as similar as possible to the aw of the measured sample. Measurements were performed on two devices (AquaLab, LabMaster), which measure aw by different principles. Based on the obtained results, we concluded that both devices give comparable results. Additionally, we also showed for both devices that residual solvents in the final products interfere with the measurement of aw.

• Keywords: Water activity, pharmaceutical dosage form, sorption isotherm, organic solvents, relative humidity influence.