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Degree of milled indomethacin amorphization and evaluation of its effect on dissolution = Stopnja amorfizacije mletega indometacina in določanje njenega vpliva na raztapljanje : Uniform Master's Pharmacy Program : enoviti magistrski študij farmacijeKrivec, Jure, farmacevtMany of the active pharmaceutical ingredients have poor solubility as the main limitation in production of a soluble and permeable pharmaceutical form. Therefore, many methods were examined to ... increase solubility in vitro and in vivo. The subject of our studies was indomethacin due to existence of many polymorphs and ability to form amorphous state, since amorphization is a viable way to increase solubility. Stable gamma indomethacin was converted into metastable alpha indomethacin, then these were used as references. We analysed complete crystallinity of these two forms with x - ray powder diffraction and differential scanning calorimetry, to confirm that they are entirely crystalline and therefore we could use them as a comparison against amorphous samples. Amorphous indomethacin was prepared by dry milling and quench cooling, sample prepared with the latter method served as a reference that is entirely amorphous. References were compared to dry - milled samples, which were performed for different sets of time; 30 minutes, 60 minutes, 180 minutes and 240 minutes. All samples were analysed with x - ray powder diffraction, differential scanning calorimetry and non - linear microscopy techniques; coherent anti- Stokes Raman scattering and sum frequency generation. Our main focus was comparing polymorphic forms, their willingness to become amorphous, moreover we compared sensitivity of analytical techniques and measuring crystalline residue in dry - milled samples. Traditional analytical techniques, particularly differential scanning calorimetry can compete with modern analytical techniques as they detected residual crystallinity in dry - milled samples, milled for 240 minutes. Data regarding glass transition temperature using traditional techniques was, however, less reliable and inconclusive. Modern non - linear microscopy techniques; sum frequency generation and coherent anti - Stokes Raman scattering microscopy, gave a lot of information and increased analytical capability. These techniques are capable of analysing samples in multiple sites and modes, we detected residual crystallinity in samples milled for 240 minutes, where sum frequency generation proved to be exceptionally sensitive. Shortcomings, such as sample burning, narrower availability and the need for specific adjustment for each sample suggest further development is in line before wider adoption. Finally, intrinsic dissolution studies indicate that despite the difference between crystalline polymorphic forms and a difference in measurements of residual crystallinity, rate of dissolution is practically similar and these differences do not reflect in dissolution with the same magnitude. Samples dry milled from gamma indomethacin for 180 minutes showed the same rate of dissolution as quench cooled amorphous indomethacin, while samples dry milled from alpha indomethacin showed the same rate of dissolution as quench cooled amorphous indomethacin after 240 minutes of milling. Milling longer than 240 minutes would be impractical. All things considered, polymorphs can behave independently and not reflect this behaviour in dissolution. Optical non - linear techniques proved to be a noteworthy tool when detecting crystalline residue and its use greatly adds to characterization of amorphous form.Vrsta gradiva - magistrsko delo ; neleposlovje za odrasleZaložništvo in izdelava - Ljubljana : [J. Krivec], 2021Jezik - angleškiCOBISS.SI-ID - 75239171
Avtor
Krivec, Jure, farmacevt
Drugi avtorji
Planinšek, Odon |
Peltonen, Leena
Teme
Topnost |
Zdravilne učinkovine |
indometacin |
amorfnost |
kristalni ostanek |
ne - linearna mikroskopija |
raztapljanje
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Knjižnica/institucija |
Kraj | Akronim | Za izposojo | Druga zaloga |
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Fakulteta za farmacijo, Ljubljana | Ljubljana | FFALJ |
v čitalnico 1 izv.
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Ime baze podatkov | Področje | Leto |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Krivec, Jure, farmacevt | ![]() |
Planinšek, Odon | 14935 |
Peltonen, Leena | ![]() |
Vir: Osebne bibliografije
in: SICRIS
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