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    Itraconazole-HPMCAS amorphous spray dried dispersions: composition and process factors impacting performance

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    Author
    Honick, Moshe Avraham
    Advisor
    Polli, James E.
    Date
    2019
    Type
    dissertation
    
    Metadata
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    Abstract
    Despite their potential for improving the oral bioavailability of poorly water soluble drugs, spray dried dispersions (SDDs) have properties that make them challenging to formulate. The objective of this dissertation was to elucidate composition and process factors for favorable SDD performance and to develop fast-, medium-, and slow-release formulations for an IVIVC study. Itraconazole (ITZ) was used as a model poorly soluble drug and hypromellose acetate succinate (HPMCAS) was used as a carrier polymer for the SDDs. Film casting proved to be a useful screening method for demonstrating the feasibility of producing amorphous SDDs of ITZ and HPMCAS as well as for rank ordering the grades of HPMCAS (i.e. HPMCAS-L > HPMCAS-M > HPMCAS-H) in terms of in-vitro dissolution performance. Producing solid oral dosage forms of ITZ-HPMCAS SDDs proved challenging due to the low particle size, poor flowability, and low bulk density of the SDDs. Initial tableting on a Natoli hand-operated press showed that drug release from tablets containing SDDs of ITZ and HPMCAS-L were very sensitive to small differences in compaction pressure and porosity. Interestingly, the same sensitivity was not observed in SDDs of ITZ and HPMCAS-M. Using a compaction simulator, reproducible fast-, medium- and slow-release tablet formulations of ITZ and HPMCAS SDDs was developed by varying polymer grade (HPMCAS-L, HPMCAS-M), slugging pressure (20, 40 MPa), and compaction pressure (70, 85, 100 MPa). The performance of SDDs was further evaluated by comparing the compaction behavior of ITZ-HPMCAS SDDs and physical mixtures of ITZ and HPMCAS. Although the compressibility of both the SDDs and physical mixtures were similar, the SDDs had a greater tendency to laminate, especially at higher compression speeds. Tablets of SDDs containing ITZ and HPMCAS-L were particularly prone to lamination compared to the SDDs containing HPMCAS-M or HPMCAS-H. Interestingly, when the SDDs were not laminated they had a greater tensile strength than tablets produced with the physical mixtures. In conclusion, there are significant challenges associated with formulating SDDs of ITZ and HPMCAS. In addition to elucidating composition and process factors impacting performance, fast-, medium-, and slow-release formulations for an IVIVC study were developed.
    Description
    2019
    Pharmaceutical Sciences
    University of Maryland, Baltimore
    Ph.D.
    Keyword
    Pharmaceutical sciences
    in vivo in vitro (IVIVC)
    spray dried dispersions
    Drug Delivery Systems
    Itraconazole
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/11698
    Collections
    Theses and Dissertations School of Pharmacy
    Theses and Dissertations All Schools

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