The crystallization inhibitor properties of different polymers in bioactive amorphous solid dispersions
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- Tez No: 403231
- Danışmanlar: Dr. LISA MAUER
- Tez Türü: Yüksek Lisans
- Konular: Kimya, Kimya Mühendisliği, Chemistry, Chemical Engineering
- Anahtar Kelimeler: Belirtilmemiş.
- Yıl: 2014
- Dil: İngilizce
- Üniversite: Purdue University
- Enstitü: Yurtdışı Enstitü
- Ana Bilim Dalı: Belirtilmemiş.
- Bilim Dalı: Belirtilmemiş.
- Sayfa Sayısı: 122
Özet
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Özet (Çeviri)
Creating and stabilizing amorphous forms of compounds with high crystallization tendencies is a challenge. However, doing so intentionally can enhance the solubility of the compound. Common food processing conditions and interactions between ingredients in complex formulations have the potential to induce amorphous structure formation in food systems intentionally or unintentionally. Understanding conditions in which the amorphization of crystalline compounds is possible, and the resulting stability and solubility traits of the amorphous structures, is important. There is often a trade-off between physical structure and stability, with the amorphous form being inherently less stable than its crystalline counterpart. The objective of this study was to use a systematic approach to create amorphous solid dispersions of two crystalline compounds with different aqueous solubility properties (curcumin and thiamine) with a selection of common GRAS polymers (guar gum, xanthan gum, pectin, κ-carrageenan, gelatin, chitosan, poly (vinylpyrrolidone) (PVP)). Curcumin was selected as a model bioactive compound with a low aqueous solubility that limits its bioavailability. Amorphization of curcumin was possible using select pharmaceutical polymers, and this study extended the solid dispersion approach to a selection of GRAS polymers including guar gum, xanthan gum, and chitosan. Rotary evaporation was used to create solid dispersions followed by cryomilling to reduce the particle size. To be able to stabilize an amorphous system via intermolecular interaction, miscibility of two compounds at a molecular level is crucial and using this approach is initiated by an aqueous media wherein both components are practically soluble. Unfortunately, a common solvent for curcumin and the natural was not found and the amorphization of curcumin in these polymers was unsuccessful. Thiamine was selected as the model water soluble crystalline compound. Although thiamine is commonly found in the crystalline deliquescent form, it is possible and likely that amorphous thiamine structures are formed by interaction with polymeric ingredients (e.g. starch, hydrocolloids). Thiamine solid dispersions were prepared using a lyophilization technique. The solid dispersions were then stored at selected temperature (25, 40 oC) and relative humidity (0, 23, 32, 54, 75, 85 % RH) conditions and monitored over time using X-ray powder diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Moisture sorption isotherms of all samples were also determined. It was possible to create amorphous solid dispersions of thiamine in some polymers whereas amorphous thiamine could not be formed in the absence of a polymer. In low RH conditions, pectin, κ-carrageenan, gelatin and guar gum were better stabilizers for thiamine amorphous solid dispersions than PVP. The thiamine dispersions in PVP crystallized immediately. Trends in crystallization inhibitor properties were based primarily on the ability of the polymer to interact with thiamine via hydrogen bonding and were less dependent on the hygroscopicity and glass transition temperature (Tg) of the polymers.
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