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In vitro-solubility and supersaturation behavior of supersaturating drug delivery systems [Elektronisk resurs]

Alhayali, Amani (författare)
Velaga, Sitaram P. (preses)
Klein, Sandra (opponent)
Luleå tekniska universitet Institutionen för hälsovetenskap (utgivare)
Alternativt namn: Institutionen för hälsovetenskap, Luleå tekniska universitet
Alternativt namn: Luleå tekniska universitet. Hälsovetenskap
Alternativt namn: Hälsovetenskap, Luleå tekniska universitet
Alternativt namn: Engelska: Luleå University of Technology. Department of Health Sciences
ISBN 978-91-7790-155-6
Luleå Luleå University of Technology 2018
Engelska.
Serie: Doctoral thesis / Luleå University of Technology 1 jan 1997 → … 1402-1544
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  • E-bokAvhandling(Diss. (sammanfattning), 2018)
Sammanfattning Ämnesord
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  • The development of new pharmaceutical products has been challenged by the growing number of poorly water-soluble drugs, which often lead to suboptimal bioavailability. Various approaches, such as the use of amor-phous solid dispersions and cocrystals, have been used to improve the solu-bility, and subsequent bioavailability, of these drug molecules. Supersaturat-ing drug delivery systems (SDDSs) have potential for achieving adequate oral drug bioavailability by increasing the drug solubility and creating a su-persaturated state in the gastrointestinal tract. However, there is a need for better understanding of the supersaturation behavior in SDDSs and of the factors affecting supersaturation. The main objective of this thesis was to improve understanding of the supersaturation solubility behavior in SDDSs with a particular focus on rapidly dissolving solid forms (amorphous forms/cocrystals). In the course of the work, a new formulation for ezetimibe using an amorphous solid dispersion was prepared, cocrystals of tadalafil were pre-pared, and oral films of silodosin were formulated for the first time. These new formulations were thoroughly characterized using a number of solid-state and pharmaceutical characterization techniques. The dissolution and supersaturation behavior of the prepared SDDSs were studied. The effects of various factors on the supersaturation and precipita-tion characteristics were investigated. These factors included the preparation method, the temperature of the dissolution medium, the type of dissolution biorelevant medium (gastric/intestinal) used, the permeability of the relevant gastrointestinal membranes, the addition of polymers, and the addition of surfactants. The amorphous solid dispersions, cocrystals and oral films that were prepared represent new drug formulations that provide significantly higher dissolution rates and supersaturated solubility than crystalline drug forms. Solid dispersions prepared by the melting method had better super-saturation properties than those prepared by spray drying. The precipitation kinetics of the solid dispersion were faster at 37 ̊C than at 25 ̊C in bio-relevant media. Implementation of an absorption tool during in vitro evalua-tion of supersaturation levels could improve the prediction accuracy of su-persaturation and precipitation. A better understanding of the effects of ex-cipients on the supersaturation and precipitation behavior of these types of formulation was obtained in this thesis. The improvement in supersaturation solubility obtained by adding polymers and surfactants was not proportional to the amounts of excipient used. This thesis has made notable contributions to the field of pharmaceutical science by advancing our understanding of the supersaturation solubility behavior of the newly prepared SDDSs. 

Ämnesord

Medical and Health Sciences  (hsv)
Health Sciences  (hsv)
Other Health Sciences  (hsv)
Medicin och hälsovetenskap  (hsv)
Hälsovetenskaper  (hsv)
Annan hälsovetenskap  (hsv)
Health Science  (ltu)
Hälsovetenskap  (ltu)
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