Wymiana masy w układach emulsji wielokrotnych

• Autorzy: Dłuska E.

Warianty tytułu

EN

Mass transfer in multiple emulsion systems

• Języki publikacji: PL

Abstrakty

PL

Prezentowana praca poświęcona jest zagadnieniu wymiany masy w hierarchicznie rozproszonych układach, takich jak emulsje wielokrotne i ich postać utrwalona – mikrosfery. Przedstawiona w niej została koncepcja jednostopniowego wytwarzania emulsji wielokrotnych oraz wyniki modelowania szybkości uwalniania składnika aktywnego (leku) z emulsji i mikrosfer, które zostały zweryfikowane doświadczalnie. Zaproponowana metoda wytwarzania emulsji wielokrotnych pozwala na otrzymywanie stabilnych struktur w krótkim czasie (kilkudziesięciu sekund) w jednym aparacie, w przeciwieństwie do tradycyjnych metod dwustopniowych. Pożądane właściwości wytwarzanych emulsji wielokrotnych (rozkład rozmiarów kropel, zawartość kropel fazy wewnętrznej w kroplach fazy membranowej) uzyskuje się poprzez dobór odpowiednich warunków hydrodynamicznych w kontaktorze helikoidalnym. Do przewidywania szybkości uwalniania składnika z emulsji wielokrotnych zaproponowano ogólny model teoretyczny transportu masy w układach rozproszonych. Założenia modelu zweryfikowano, opierając się na przeprowadzonych badaniach doświadczalnych uwalniania. Celem badań było określenie wpływu struktury emulsji wielokrotnych (rozmiary kropel i ich upakowanie), powiązanej z warunkami ich wytwarzania, oraz oporów transportu w zewnętrznym środowisku uwalniania na szybkość i charakter profili uwalniania. Stwierdzono istotny wpływ obu tych czynników na szybkość uwalniania leku z emulsji wielokrotnych. Badania uwalniania potwierdziły zakładany mechanizm dyfuzyjnego uwalniania składnika aktywnego z emulsji wielokrotnych. W przypadku uwalniania leku z mikrosfer, otrzymywanych w wyniku chemiczno-termicznego utrwalania emulsji, struktura mikrosfer oraz warunki wnikania w fazie zewnętrznej miały wpływ zarówno na szybkość uwalniania, jak i na charakter profili uwalniania. Podczas badań stwierdzono dwuetapową kinetykę procesu, tj. wstępne i zasadnicze uwalnianie. Występowanie etapu wstępnego i czas jego trwania zależały od intensywności mieszania środowiska zewnętrznego. Analiza efektów erozji stałej fazy membranowej (matrycy) pozwoliła na identyfikację mechanizmu erozji homogenicznej. Wyniki badań uwalniania leku z emulsji wielokrotnych przedyskutowano, opierając się na ogólnym modelu teoretycznym. W toku analizy danych doświadczalnych i wyników modelowania, występującemu w modelu ogólnym objętościowemu współczynnikowi wnikania nadano sens parametru struktury. Parametr ten jest właściwy dla danej klasy emulsji, tj. emulsji wytwarzanej w określonych warunkach, zachowuje w odniesieniu do niej wartość stałą i pochodzi z optymalizacji danych doświadczalnych. Znajomość parametru struktury umożliwia poprawne przewidywanie szybkości uwalniania. Podobny wzorzec modelowania obowiązywał dla mikrosfer, w przypadku których model zaproponowany do przewidywania szybkości uwalniania stanowił rozwinięcie modelu słusznego dla emulsji wielokrotnych. Model ten uwzględnia zidentyfi kowany mechanizm erozji matrycy mikrosfer i na podstawie doświadczalnie określonego parametru zmian struktury pozwala na przewidywanie szybkości uwalniania dyfuzyjno-erozyjnego. Ze względu na uniwersalną formułę równań bilansowych, zaproponowany model umożliwia przewidywanie kinetyki uwalniania z różnych systemów typu matrycowego (uwalnianie dwuetapowe lub pulsujące) przez sprzężenie identycznych układów równań odpowiednimi warunkami brzegowo-początkowymi.

EN

The paper deals with mass transfer in hierarchical dispersed systems, such as multiple emulsions and microspheres. The preparation and stabilization method of multiple emulsions entrapping an active agent and results of release process modelling were discussed. The proposed method of multiple emulsions preparation is a one-step method in contrast to the classical two-step procedure. Stable multiple emulsions are formed within only several seconds. Multiple emulsions of required characteristics (drop size distribution, volume fraction of internal droplets and encapsulation efficiency of active agent) are formed depending on the operating parameters in the helical contactor. Key factors affecting multiple emulsion preparation were : phases ratio, rotational flow and annular gap width. The operating conditions were optimized to find the best characteristic multiple emulsions (the largest interfacial area) for release experiments. For interpretation of experimental data and prediction of release profiles from multiple emulsions and microspheres, a theoretical model has been proposed and developed. The presented mass transfer model accounts for the internal structure of delivery system and hydrodynamic conditions of the surrounding release medium. The model was validated by experimental data of an active agent (drug) release from multiple emulsions and microspheres obtained via multiple emulsions thermal cross linking and hardening. The experimental results of release profiles indicated the importance of the internal structure of multiple emulsions/microspheres, as well as intensity of external surrounding mixing on the release rate. The mathematical model of the release process from multiple emulsions corresponds to active agent diffusion inside the drops of membrane phase. For describing the release process from microspheres, a theoretical model was developed to account for the validated mechanism of the release process. This model considers the release process via combined erosion and diffusion within polymeric matrix exhibiting two-stage release kinetics of primary release with induction phase and continuous release. Experimental analysis of erosion effects indicated homogenous erosion mechanism. Quantitative analysis of the model simulations showed that the volumetric mass transfer coefficient characterizing the emulsion/microsphere structure must be optimized from experimental data. When we know the values of this parameter for the specified classes of product structures, we can predict the release rate for similar structures and about the same during loading at any release conditions without the need for exploratory in vitro experiments. The model developed for the prediction of release kinetics from eroding delivery systems exhibiting two-stage release patterns can also be used for pulsatile release process designing.

Słowa kluczowe

PL

emulsje wielokrotne/mikrosfery ze składnikiem aktywnym; wytwarzanie emulsji wielokrotnych i mikrosfer; kinetyka procesu uwalniania; modelowanie uwalniania składnika

EN

multiple emulsions/microspheres with active agent; multiple emulsions and microspheres preparation; mechanisms of release process of active agent; kinetics of release process; modelling of release process

• Wydawca: Oficyna Wydawnicza Politechniki Warszawskiej
• Czasopismo: Prace Wydziału Inżynierii Chemicznej i Procesowej Politechniki Warszawskiej
• Rocznik: 2011
• Tom: Vol. 35, z. 2
• Strony: 3--126
• Opis fizyczny: Bibliogr. 344 poz., tab., rys., wykr.

Twórcy

autor

Dłuska E.

• Zakład Kinetyki i Termodynamiki Procesowej

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