| 1. |
- Briggner, Lars-Erik, et al.
(författare)
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In Silico Solid State Perturbation for Solubility Improvement
- 2014
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Ingår i: ChemMedChem. - : Wiley. - 1860-7179 .- 1860-7187. ; 9:4, s. 724-726
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Tidskriftsartikel (refereegranskat)abstract
- Solubility is a frequently recurring issue within pharmaceutical industry, and new methods to proactively resolve this are of fundamental importance. Here, a novel methodology is reported for intrinsic solubility improvement, using insilico prediction of crystal structures, by perturbing key interactions in the crystalline solid state. The methodology was evaluated with a set of benzodiazepine molecules, using the two-dimensional molecular structure as the only a priori input. The overall trend in intrinsic solubility was correctly predicted for the entire set of benzodiazepines molecules. The results also indicate that, in drug compound series where the melting point is relatively high (i.e., brick dust compounds), the reported methodology should be very suitable for identifying strategically important molecular substitutions to improve solubility. As such, this approach could be a useful predictive tool for rational compound design in the early stages of drug development.
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| 2. |
- Briggner, Lars-Erik, et al.
(författare)
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Solid-State Perturbation for Solubility Improvement : A Proof of Concept
- 2011
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Ingår i: ChemMedChem. - : Wiley. - 1860-7179. ; 6:1, s. 60-62
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Tidskriftsartikel (refereegranskat)abstract
- Simple and rational: The intrinsic solubility of a compound can be systematically improved by perturbing key interactions in its crystal structure. By carefully choosing the perturbation, the end result will be a molecule similar to the original one, but with significantly higher solubility. This methodology is demonstrated on a subset of benzodiazepines, resulting in significant improvement of their solubility.
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| 3. |
- Briggner, Lars-Erik, et al.
(författare)
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Design and testing of a small-scale sublimation apparatus
- 2009
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Ingår i: Journal of Thermal Analysis and Calorimetry. - : Springer Science and Business Media LLC. - 1588-2926 .- 1388-6150 .- 1572-8943. ; 98:1, s. 331-335
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Tidskriftsartikel (refereegranskat)abstract
- In many areas of scientific research and development, for example in the pharmaceutical industry, it is important to prepare and to characterize crystals of pure organic compounds which are thermodynamically stable. The formation of crystals from the gas phase is technically less straightforward than crystallisation from solution, but sublimation techniques can have several important features. In the present paper we report the design and testing of a novel apparatus for small scale sublimation and fractional deposition of crystals. The instrument has been developed with special reference to the needs in the pharmaceutical industry. A few mg of the samples are enclosed, under reduced pressure, in thin-walled glass tubes, along which a well defined temperature gradient can be formed. During an experiment the substance will sublime from the hot end of the glass tube and crystals will be deposited along the temperature gradient. The applicability of the instrument has been verified by experiments with several test compounds. Results from experiments with carbamazepine, are reported in some detail. Carbamazepine single crystals of high quality were obtained and the transition temperature between the triclinic (Form I) and the monoclinic (Form III) crystal modifications agreed with literature values.
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| 4. |
- Digaitis, Ramūnas, PhD, et al.
(författare)
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Hydration and dehydration induced changes in porosity of starch microspheres
- 2022
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Ingår i: Carbohydrate Polymers. - : Elsevier. - 0144-8617 .- 1879-1344. ; 291, s. 119542-119542
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Tidskriftsartikel (refereegranskat)abstract
- Characterization and tuning of the porosity of amorphous starch materials are important for many applications, including controlled release of encapsulated proteins. The porosities of these materials in dry and hydrated states can have different physicochemical origins and properties. Here, porosities of dry cross-linked starch microspheres and their hydration-induced transformations were characterized by small angle X-ray scattering, scanning electron and optical microscopies, thermogravimetric analysis, sorption calorimetry, nitrogen sorption, and helium-pycnometry. The analyses revealed that dry microspheres consist of porous cores with pore diameters below 100 nm and shells which appeared to be denser but contained wider pores (100–300 nm). The outer crust of the microspheres shell is non-porous, which restricts diffusion of nitrogen, water, and ethanol. Partial hydration triggered an irreversible collapse of dry porosity at 12 wt% water. Further hydration resulted in interfacial changes and promoted wet porosity, related to characteristic distances between polymer chains.
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| 5. |
- Kocherbitov, Vitaly, et al.
(författare)
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Hydration of a natural polyelectrolyte xanthan gum : Comparison with non-ionic carbohydrates
- 2010
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Ingår i: Carbohydrate Polymers. - : Elsevier. - 0144-8617 .- 1879-1344. ; 82:2, s. 284-290
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Tidskriftsartikel (refereegranskat)abstract
- In dilute solutions, polyelectrolytes exhibit more hydrophilic properties than non-charged polymers do. However, extension of this statement on almost dry systems is questionable. In this study we present sorption calorimetric data on hydration of a natural carbohydrate polyelectrolyte xanthan gum and make comparison with analogous data of three types of cellulose which is a non-charged carbohydrate polymer. An analysis of the sorption isotherm shows that at given relative humidities xanthan gum absorbs greater amount of water than non-charged cellulose does. Nonetheless, the enthalpies of hydration of xanthan gum and of all three considered types of cellulose at zero water content are equal to −18 kJ/mol. Thus, entropy of hydration plays an important role in water sorption behaviour of xanthan gum. The apparent absence of an ion effect on polymer–water interactions can be explained by solvation of ions by OH-groups of the dry xanthan gum. Ab initio calculations presented here show that solvation of an ionic group of xanthan gum by a carbohydrate hydroxyl is as strong as hydration of the same group by water. The exothermic heat effect of hydration arises from the loss of the mobility of water on the rigid glassy environment of the polymer. For the first time, the glass transition temperature of dry xanthan gum is reported to be 60 °C.
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