| 21. |
- Alomari, Mustafa, et al.
(författare)
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Printing of T3 and T4 Oral Drug Combinations as a Novel Strategy for Hypothyroidism
- 2018
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Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 549:1-2, s. 363-369
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Tidskriftsartikel (refereegranskat)abstract
- Hypothyroidism is a chronic and debilitating disease that is estimated to affect 3% of the general population. Clinical experience has highlighted the synergistic value of combining triiodothyronine (T3) and thyroxine (T4) for persistent or recurrent symptoms. However, thus far a platform that enables the simultaneous and independent dosing of more than one drug for oral administration has not been developed. Thermal inkjet (TIJ) printing is a potential solution to enable the dual deposition of T3 and T4 onto orodispersible films (ODFs) for therapy personalisation. In this study, a two-cartridge TIJ printer was modified such that it could print separate solutions of T3 and T4. Dose adjustments were achieved by printing solutions adjacent to each other, enabling therapeutic T3 (15–50 μg) and T4 dosages (60–180 μg) to be successfully printed. Excellent linearity was observed between the theoretical and measured dose for both T3 and T4 (R2 = 0.982 and 0.985, respectively) by changing the length of the print objective (Y-value). Rapid disintegration of the ODFs was achieved (< 45 seconds). As such, this study for the first time demonstrates the ability to produce personalised dose combinations by TIJ printing T3 and T4 onto the same substrate for oral administration.
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| 22. |
- Andersen, Anders J., et al.
(författare)
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Characterization of salmon calcitonin in spray-dried powder for inhalation : effect of formulation and process variables
- 2006
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Ingår i: 2006 AAPS Annual Meeting and Exposition. - : American Association of Pharmaceutical Scientists.
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Konferensbidrag (refereegranskat)abstract
- To characterize physicochemical properties of salmon calcitonin in spray-dried powder for inhalation and understand the interplay between stability, formulation and process parametersSalmon calcitonin (sCT) was spray-dried together with mannitol and chitosan that acts as stabiliser and absorption enhancer, respectively. Two process variables, i.e. inlet temperature and atomizing air volumetric flow rate, were investigated. Solid state properties of the spray-dried powders were characterized using SEM, TGA, XRPD and DSC. The physicochemical stability of salmon calcitonin in the dry powder was investigated by FTIR, HPLC and LC-MS techniques.A high yield of up to 80 % spray-dried powder was obtained with an improved cyclone assembled with B-290 Mini Spray Drier. Nevertheless, the yield was markedly reduced when addition of chitosan exceeded a certain proportion in spray drying formulation. XRPD and DSC results indicated that crystallinity of mannitol was inhibited with an increase of chitosan in the formulation. Residual moisture levels in the spray dried powders were 1-2%. As indicated by FTIR analysis, sCT retained its structural integrity under the spray drying conditions studied, i.e. 100-180 ºC inlet temperature and 357-742 L/h atomizing air volumetric flow rate. Addition of mannitol and chitosan in the spray drying formulation did not improve stabilization of sCT, in which around 7 % degraded impurities were found at a condition of 180 ºC inlet temperature. Yet no obvious degraded impurities were found in plain sCT spray-dried powder under the conditions studied. The LC-MS analysis showed that oxidation was the main degradation pathway at high inlet temperature. Other minor impurities originated from deamidation of Asn26, N-O acyl migration on Ser29 and dimerization by cross-linkage of the disulfide bonds. Two fragments, i.e. H-(Cys1-Gly28)-OH and H-(Ser29-Pro32)-NH2, could also be found when the degraded ester bond between Gly28 and Ser29 was further hydrolysed in phosphate buffer.Salmon calcitonin can be spray-dried into dry powders with good physical integrity under certain conditions. Chemical stability of sCT in spray-dried powder could be improved by the optimization of formulation and process variables.
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| 23. |
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| 24. |
- Ariane, Mostapha, et al.
(författare)
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Discrete multi-physics simulations of diffusive and convective mass transfer in boundary layers containing motile cilia in lungs
- 2018
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Ingår i: Computers in Biology and Medicine. - : Elsevier. - 0010-4825 .- 1879-0534. ; 95, s. 34-42
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, the mass transfer coefficient (permeability) of boundary layers containing motile cilia is investigated by means of discrete multi-physics. The idea is to understand the main mechanisms of mass transport occurring in a ciliated-layer; one specific application being inhaled drugs in the respiratory epithelium. The effect of drug diffusivity, cilia beat frequency and cilia flexibility is studied. Our results show the existence of three mass transfer regimes. A low frequency regime, which we called shielding regime, where the presence of the cilia hinders mass transport; an intermediate frequency regime, which we have called diffusive regime, where diffusion is the controlling mechanism; and a high frequency regime, which we have called convective regime, where the degree of bending of the cilia seems to be the most important factor controlling mass transfer in the ciliated-layer. Since the flexibility of the cilia and the frequency of the beat changes with age and health conditions, the knowledge of these three regimes allows prediction of how mass transfer varies with these factors.
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| 25. |
- Basavoju, Srinivas, et al.
(författare)
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Crystal Structures of Hydrates of Norfloxacin
- 2006
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Ingår i: 2006 AAPS Annual Meeting and Exposition. - : American Association of Pharmaceutical Scientists.
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Konferensbidrag (refereegranskat)abstract
- Description: Purpose: The aim was to identify new phases of norfloxacin and to analyse their crystal structures. Methods: Norfloxacin was crystallized in methanol under various conditions using solvent-drop grinding method. The single crystal X-ray diffraction data sets were collected on a Bruker Nonius Kappa CCD, using Mo Kα radiation (λ = 0.71073 Å). Results: Norfloxacin mono-and trihydrates were identified. Mono and trihydrates crystallize in Pbca, P21/c space groups respectively. One of the water molecules in trihydrate is in disorder. In these structures, inversion related norfloxacin molecules form stacked layers with quinolone moieties and stabilized by ππ (3.449 to 4.016 Å) interactions. The norfloxacin molecules in stacked layers generate hydrophilic channels to include water molecules through O-HO, O-HO¯ and N-HO¯ interactions. A significant difference in the torsional angles of the piperazinyl ring of norfloxacin in mono-, di- (reported), and trihydrate was evident for conformational flexibility. Conclusion: We report crystal structures of mono and trihydrates of norfloxacin that are channel hydrates. Norfloxacin may exhibit conformational polymorphism
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| 26. |
- Basavoju, Srinivas, et al.
(författare)
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Indomethacin-saccharin cocrystal : design, synthesis and preliminary pharmaceutical characterization
- 2008
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Ingår i: Pharmaceutical research. - : Springer. - 0724-8741 .- 1573-904X. ; 25:3, s. 530-541
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. To design and prepare cocrystals of indomethacin using crystal engineering approaches, with the ultimate objective of improving the physical properties of indomethacin, especially solubility and dissolution rate. Materials and Methods. Various cocrystal formers, including saccharin, were used in endeavours to obtain indomethacin cocrystals by slow evaporation from a series of solvents. The melting point of crystalline phases was determined. The potential cocrystalline phase was characterized by DSC, IR, Raman and PXRD techniques. The indomethacin-saccharin cocrystal (hereafter IND-SAC cocrystal) structure was determined from single crystal X-ray diffraction data. Pharmaceutically relevant properties such as the dissolution rate and dynamic vapour sorption (DVS) of the IND-SAC cocrystal were evaluated. Solid state and liquid-assisted (solvent-drop) cogrinding methods were also applied to indomethacin and saccharin. Results. The IND-SAC cocrystals were obtained from ethyl acetate. Physical characterization showed that the IND-SAC cocrystal is unique vis-a-vis thermal, spectroscopic and X-ray diffraction properties. The cocrystals were obtained in a 1:1 ratio with a carboxylic acid and imide dimer synthons. The dissolution rate of IND-SAC cocrystal system was considerably faster than that of the stable indomethacin gamma-form. DVS studies indicated that the cocrystals gained less than 0.05% in weight at 98%RH. IND-SAC cocrystal was also obtained by solid state and liquid-assisted cogrinding methods. Conclusions. The IND-SAC cocrystal was formed with a unique and interesting carboxylic acid and imide dimer synthons interconnected by weak N-H center dot center dot center dot O hydrogen bonds. The cocrystals were non-hygroscopic and were associated with a significantly faster dissolution rate than indomethacin (gamma-form).
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| 27. |
- Basavoju, Srinivas, et al.
(författare)
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Pharmaceutical Co-crystallization of Norfloxacin
- 2006
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Ingår i: 2006 AAPS Annual Meeting and Exposition. - : American Association of Pharmaceutical Scientists.
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Konferensbidrag (refereegranskat)abstract
- Description: Aim: The objective of the study was to prepare co-crystal and salts of norfloxacin and to investigate their structural and pharmaceutical properties. Methods: Norfloxacin was crystallized in a series of solvents in an effort to investigate the polymorphism. Norfloxacin was also co-crystallized with isonicotinamide and succinic acid in different solvents. We have characterised these materials using DSC, IR, Raman and PXRD. The single crystal X-ray diffraction data was obtained and crystal structures were solved. The solubility and moisture sorption behaviour (0-90%RH) of these materials were determined. Results: Norfloxacin Anhydrate, 1 crystallizes in the triclinic P-1 space group with one neutral molecule in the asymmetric unit. The carboxylic acid group participates in the intramolecular O-HO (D=2.525 Å) hydrogen bonding with carbonyl group of the quinolone moiety. NorfloxacinIsonicotinamideCHCl3, 2 crystallizes in the centrosymmetric C2/c space group with one molecule of norfloxacin, one molecule of isonicotinamide and one molecule of CHCl3.in the asymmetric unit. Four molecules of norfloxacin generate a rectangular host type network with N-HO (D=2.668 Å) and N-HO (D=2.657 Å) interactions. Two isonicotinamide molecules form robust amideamide (N-HO, D=2.889 Å) homodimer synthon and fits into the rectangular grid (N-HO, D=2.929 Å). The CHCl3 molecules lie in the channels of the host frame work. Norfloxacin (Succinate)0.5 Hydrate, 3 crystallizes in the triclinic P-1 space group with one norfloxacin cation, half molecule of succinate dianion and one H2O molecule in the asymmetric unit. The two succinate anions and two norfloxacin cations form a cyclic tetramer synthon (N-HO, D=2.726 Å) and extends with H2O molecules through the hydrophilic channel generated by quinolone stacked layers (ππ, 4.041 Å) along the a-axis via O-HO (D=2.928 Å) interactions. The rank order of the solubility of these materials was 1<2
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| 28. |
- Basavoju, Srinivas, et al.
(författare)
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Pharmaceutical cocrystal and salts of norfloxacin
- 2006
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 6:12, s. 2699-2708
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the structural and pharmaceutical properties of norfloxacin (a poorly soluble antibacterial drug), its cocrystal, and salts. Norfloxacin in the anhydrous form (form A, 1) was crystallized. It was cocrystallized with isonicotinamide (2), and organic salts were prepared with succinic acid, malonic acid, and maleic acid (3-5, respectively). These phases were characterized by differential scanning calorimetry (DSC), infrared (IR) and Raman spectroscopy, and powder X-ray diffraction (PXRD). Single-crystal X-ray diffraction data were obtained, and crystal structures were solved. The apparent solubility of these phases was determined. Robust O-H⋯O, O-H⋯O-, O-H⋯N, N-H⋯O, N+-H-O -, and N-H⋯N interactions were present in all these structures. Quinolone moieties in these structures stack with π⋯π interactions and form channels to include CHCl3 or H2O. Herein we report a new cocrystal and salts of norfloxacin with improved aqueous solubility
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| 29. |
- Basavoju, Srinivas, et al.
(författare)
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Pharmaceutical salts of fluoroquinolone antibacterial drugs with acesulfame sweetener
- 2012
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Ingår i: Molecular Crystals and Liquid Crystals. - : Informa UK Limited. - 1542-1406 .- 1563-5287. ; 562:1, s. 254-264
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Tidskriftsartikel (refereegranskat)abstract
- Novel organic salts of norfloxacin and ciprofloxacin with artificial sweeteners such as saccharin and acesulfame were prepared. The two salts 1 and 2 were characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Finally, the crystal structures were solved by single crystal X-ray diffraction data and the structures were analyzed in terms of supramolecular synthons. In norfloxacin acesulfamate 1, two norfloxacin cations and two acesulfame anions form an eight membered cyclic tetramer supramolecular synthon. The salt, ciprofloxacin acesulfamate 2, has a similar structure as salt 1. This study contributes the importance of crystal engineering and supramolecular chemistry to the pharmaceutical applications in terms of interactions and structural correlations in the design of new solid phases. Supplemental materials are available for this article. Go to the publisher's online edition of Molecular Crystals and Liquid Crystals to view the free supplemental file.
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| 30. |
- Bradley, Jonathan P., et al.
(författare)
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Probing intermolecular crystal packing in gamma-indomethacin by high-resolution 1H solid-state NMR spectroscopy
- 2011
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 11:8, s. 3463-3471
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Tidskriftsartikel (refereegranskat)abstract
- An NMR crystallography approach that combines experimental solid-state magic-angle-spinning (MAS) NMR with calculation is applied to the gamma polymorph of the pharmaceutical molecule, indomethacin. First-principles calculations (GIPAW) for the full crystal structure and an isolated molecule show changes in the (1)H chemical shift for specific aliphatic and aromatic protons of over -1 ppm that are due to intermolecular CH-pi interactions. For the OH proton, (1)H double-quantum (DQ) CRAMPS (combined rotation and multiple-pulse spectroscopy) spectra reveal intermolecular H-H proximities to the OH proton of the carboxylic acid dimer as well as to specific aromatic CH protons. The enhanced resolution in (1)H DQ-(13)C spectra, recorded at 850 MHz, enables separate (1)H DQ build-up curves (as a function of the DQ recoupling time) to be extracted for the aromatic CH protons. Supported by eight-spin density-matrix simulations, it is shown how the relative maximum intensities and rates of build-up provide quantitative insight into intramolecular and intermolecular H-H proximities that characterize the crystal packing
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