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  • Development of dry emulsion production methods and compositions intended for delivery of highly lipophilic drugs : doctoral thesis = Razvoj metod izdelave in sestave posušenih emulzij za dostavljanje zdravilnih učinkovin z izrazito lipofilnimi lastnostmi : doktorska disertacija
    Pohlen, Mitja
    Dry emulsions are lipid drug delivery systems, where in the process of drying the outer water phase of an oil-in-water emulsion is being replaced with different matrix formers. Currently, dry ... emulsions are neglected in drug delivery, as they often provide low drug loading and exhibit poor flow properties, consequently, there is a need to improve dry emulsion formulation and/or find alternative methods of production. The main objective of this doctoral thesis was to resolve challenges of utilizing dry emulsions for the delivery of highly lipophilic drugs. In the first part, fluid bed layering was established as a new, alternative method for dry emulsion production. It was demonstrated that the modified Wurster chamber with swirl air flow generator was needed to successfully perform layering experiments. Based on results of microscopy techniques, we were able to confirm that oil phase was homogeneously dispersed in distinct oil droplets within the solid matrix of the pellet coating. Mixture design methodology was successfully employed to optimize stability and reconstitution ability of the dry emulsion layered pellets. Dry emulsion coated pellets provided good flow properties and increased dissolution performance of the model drug simvastatin with low water solubility. In the second part, process and dry emulsion formulation optimization was attempted in combination with spray drying method, as commonly used method for dry emulsion preparation. Nozzle geometry was identified, as a novel process parameter and its extensive effect on all critical quality attributes of dry emulsion powder was confirmed. Utilizing response surface methodology, five optimized products were produced with adequate process yield, particle size distribution, reconstitution ability and improved dissolution profile. However, dry emulsion powders provided poor flow properties. To further optimize flowability and reconstitution ability of spray dried dry emulsions, nanocrystalline cellulose and macroporous silica were introduced in the formulation as insoluble matrix formers. It was shown that macroporous silica had a positive effect on dry emulsion reconstitution ability and flow properties, due to its porous nature and large particles size, yet it partially trapped the oil-simvastatin solution within its pores. Nanocrystalline cellulose eased oil release, but due to its shape, impaired product flow properties. The last part of experimental work focuses on the comparison of fluid bed layering and spray drying as technologies for the production of dry emulsions. Fluid bed layering excelled in all studied responses, namely process yield, encapsulation efficiency, dry emulsion particle size, reconstituted emulsion droplet size distribution, and relative drug chemical stability, except for the maximum drug loading, where spray drying allowed for broader formulation changes and thus higher drug loads. In the conducted bioavailability study in rats, dry emulsion layered pellets provided a remarkable increase in relative bioavailability of 115 %, compared with the reference physical mixture with simvastatin. This work provides an in depth study of dry emulsion systems and their methods of production. The obtained results facilitate dry emulsion production method selection and enable wider use of dry emulsion systems for delivery of lipophilic drugs as they give insight into process and formulation understanding.
    Vrsta gradiva - disertacija ; neleposlovje za odrasle
    Založništvo in izdelava - Ljubljana : [M. Pohlen], 2021
    Jezik - angleški, slovenski
    COBISS.SI-ID - 83339267

    Povezava(-e):

    Repozitorij Univerze v Ljubljani – RUL
    Digitalna knjižnica Slovenije - dLib.si

    Dostop z namenskih računalnikov v prostorih NUK



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