Spelling suggestions: "subject:"marketability"" "subject:"wetability""
1 |
Cocrystal habit engineering to improve drug dissolution and alter derived powder propertiesSerrano, D.R., O'Connell, P., Paluch, Krzysztof J., Walsh, D., Healy, A.M. January 2016 (has links)
No / OBJECTIVES: Cocrystallization of sulfadimidine (SDM) with suitable coformers, such as 4-aminosalicylic acid (4-ASA), combined with changes in the crystal habit can favourably alter its physicochemical properties. The aim of this work was to engineer SDM : 4-ASA cocrystals with different habits to investigate the effect on dissolution, and the derived powder properties of flow and compaction. METHODS: Cocrystals were prepared in a 1 : 1 molar ratio by solvent evaporation using ethanol (habit I) or acetone (habit II), solvent evaporation followed by grinding (habit III) and spray drying (habit IV). KEY FINDINGS: Powder X-ray diffraction showed Bragg peak position was the same in all the solid products. The peak intensity varied, indicating different preferred crystal orientation confirmed by SEM micrographs: large prismatic crystals (habit I), large plate-like crystals (habit II), small cube-like crystals (habit III) and microspheres (habit IV). The habit III exhibited the fasted dissolution rate; however, it underwent a polymorphic transition during dissolution. Habits I and IV exhibited the highest Carr's compressibility index, indicating poor flowability. However, habits II and III demonstrated improved flow. Spray drying resulted in cocrystals with improved compaction properties. CONCLUSIONS: Even for cocrystals with poor pharmaceutical characteristics, a habit can be engineered to alter the dissolution, flowability and compaction behaviour.
|
2 |
Cocrystal habit engineering to improve drug dissolution and alter derived powder propertiesSerrano, D.R., O'Connell, P., Paluch, Krzysztof J., Walsh, D., Healy, A.M. 26 September 2015 (has links)
Yes / Objectives: Cocrystallization of sulfadimidine (SDM) with suitable coformers, such as 4-aminosalicylic acid (4-ASA), combined with changes in the crystal habit can favourably alter its physicochemical properties. The aim of this work was to engineer SDM:4-ASA cocrystals with different habits in order to investigate the effect on dissolution, and the derived powder properties of flow and compaction.
Methods: Cocrystals were prepared in a 1:1 molar ratio by solvent evaporation using ethanol (habit I) or acetone (habit II), solvent evaporation followed by grinding (habit III) and spray-drying (habit IV).
Key findings: Powder X-ray diffraction showed Bragg peak position was the same in all the solid products. The peak intensity varied, indicating different preferred crystal orientation confirmed by SEM micrographs: large prismatic crystals (habit I), large plate-like crystals (habit II), small cube-like crystals (habit III) and microspheres (habit IV). The habit III exhibited the fasted dissolution rate; however, it underwent a polymorphic transition during dissolution. Habits I and IV exhibited the highest Carr’s compressibility index, indicating poor flowability. However, habits II and III demonstrated improved flow. Spray drying resulted in cocrystals with improved compaction properties.
Conclusions: Even for cocrystals with poor pharmaceutical characteristics, a habit can be engineered to alter the dissolution, flowability and compaction behavior. / Science Foundation Ireland. Grant Number: SFI/12/RC/2275
|
3 |
Impact of alternative solid state forms and specific surface area of high-dose, hydrophilic active pharmaceutical ingredients on tabletabilityPaluch, Krzysztof J., Tajber, L., Corrigan, O.I., Healy, A.M. 20 August 2013 (has links)
Yes / In order to investigate the effect of using different
solid state forms and specific surface area (TBET) of active
pharmaceutical ingredients on tabletability and dissolution
performance, the mono- and dihydrated crystalline forms of
chlorothiazide sodium and chlorothiazide potassium (CTZK)
salts were compared to alternative anhydrous and amorphous
forms, as well as to amorphous microparticles of chlorothiazide
sodium and potassium which were produced by spray drying and
had a large specific surface area. The tablet hardness and tensile
strength, porosity, and specific surface area of single-component,
convex tablets prepared at different compression pressures were characterized. Results confirmed the complexity of the
compressibility mechanisms. In general it may be concluded that factors such as solid-state form (crystalline vs amorphous), type
of hydration (presence of interstitial molecules of water, dehydrates), or specific surface area of the material have a direct impact
on the tabletability of the powder. It was observed that, for powders of the same solid state form, those with a larger specific
surface area compacted well, and better than powders of a lower surface area, even at relatively low compression pressures.
Compacts prepared at lower compression pressures from high surface area porous microparticles presented the shortest times to
dissolve, when compared with compacts made of equivalent materials, which had to be compressed at higher compression
pressures in order to obtain satisfactory compacts. Therefore, materials composed of nanoparticulate microparticles (NPMPs)
may be considered as suitable for direct compaction and possibly for inclusion in tablet formulations as bulking agents, APIs,
carriers, or binders due to their good compactibility performance / Solid State Pharmaceutical Cluster (SSPC), supported by Science Foundation Ireland under Grant No. 07/SRC/B1158.
|
4 |
A novel approach to crystallisation of nanodispersible microparticles by spray drying for improved tabletabilityPaluch, Krzysztof J., Tajber, L., Adamczyk, B., Corrigan, O.I., Healy, A.M. 15 June 2012 (has links)
Yes / High-dose API powders which are to be tableted by direct compression should have high compactibility and compressibility. This note reports on a novel approach to the manufacture of crystalline powders intended for direct compaction with improved compactibility and compressibility properties. The poorly compactable API, chlorothiazide, was spray dried from a water/acetone solvent mix producing additive-free nanocrystalline microparticles (NCMPs) of median particle size 3.5 μm. Tablets compacted from NCMPs had tensile strengths ranging from 0.5 to 4.6 MPa (compared to 0.6–0.9 MPa for tablets of micronised CTZ) at compression forces ranging from 6 kN to 13 kN. NCMP tablets also had high porosities (34–20%) and large specific surface areas (4.4–4.8 m2/g). The time taken for tablets made of NCMPs to erode was not statistically longer (p > 0.05) than for tablets made of micronised CTZ. Fragmentation of NCMPs on compression was observed. The volume fraction of particles below 1 μm present in the suspension recovered after erosion of NCMP tablets was 34.8 ± 3.43%, while no nanosized particles were detected in the slurry after erosion of compacted micronised CTZ. / Solid State Pharmaceutical Cluster (SSPC), supported by Science Foundation Ireland under grant number 07/SRC/B1158.
|
5 |
Crystal Engineering of Pharmaceuticals: Modulating Physicochemical Properties of Active Ingredients by the Formation of CocrystalsJhariya, Aditya N. January 2021 (has links)
Pharmaceuticals with suitable therapeutic properties often found to encounter
challenges with dosage form development due to their poor physicochemical
properties. Aim of thesis is to evaluate potential of crystal engineering directed
cocrystallisation of active ingredients in modulating their physical attributes. The
model compounds considered are isoniazid, caffeine, nifedipine, glyburide,
chlorpropamide and riboflavin. Co-formers selected are based on the suitability
of functional groups for hydrogen bond formation. Co-crystal screening and
preparation methods used include neat grinding (NG), liquid assisted grinding
(LAG) and solution crystallisation.
Antituberculosis drug, isoniazid, upon cocrystallisation with melamine, solubility
has reduced as per high performance liquid chromatography assay, however,
antimicrobial properties determined using REMA assay confirms that cocrystal
anti-mycobacterial activity is not compromised. Next, caffeine-glutaric acid
cocrystal polymorphic forms (Forms I and II) subjected to mechanical property evaluations in multiple faces using nanoindentation and correlated relationship
between crystal structure and mechanical property. The results suggest that
metastable form, Form I, could display suitable tablet properties to that of
thermodynamically stable form, Form II. Subsequently, photosensitive drug,
nifedipine, cocrystallised with theophylline and caffeine. Notably, photochemical
stability along with solubility and drug release of cocrystals is found to be
superior to that of nifedipine. Lastly, crystal engineering principles utilised in
preparation of multicomponent crystals of antidiabetic model drugs, glyburide
and chlorpropamide with various coformers. Interestingly, during the preparation
of chlorpropamide-2-nitrobenzyl alcohol, high Z prime crystal (Z’=3) of 2-
nitrobenzyl alcohol is serendipitously identified. In conclusion, crystal
engineering based cocrystallisation is a viable technology for modulating
physicochemical properties of pharma and nutraceuticals.
|
6 |
Ultrasound assisted processing of solid state pharmaceuticals : the application of ultrasonic energy in novel solid state pharmaceutical applications, including solvent free co-crystallisation (SFCC) and enhanced compressibilityAlwati, Abdolati A. M. January 2017 (has links)
The objective of this study was to develop a new method for co-crystal preparation which adhered to green chemistry principles, and provided advantages over conventional methods. A novel, solvent-free, high-power ultrasound (US) technique, for preparing co-crystals from binary systems, was chosen as the technology which could fulfil these aims. The application of this technology for solid state co-crystal preparation was explored for ibuprofen-nicotinamide (IBU-NIC), carbamazepine-nicotinamide (CBZ-NIC) and carbamazepine-saccharin (CBZ-SAC) co-crystals. The effect of different additives and processing parameters such as power level, temperature and sonication time on co-crystallisation was investigated. Characterisation was carried out using DSC, PXRD, FTIR, Raman and HPLC. In addition, an NIR prediction model was developed and combined with multivariate analysis (PLS) and chemometric pre-treatments. It was found to be a robust, reliable and rapid method for the determination of co-crystal purity for the IBU-NIC and CBZ-NIC pairs. Co-crystal quantification of US samples helped to optimise the US method. Finally, a model formulation of paracetamol containing 5% and 10% PEG 8000 was ultrasonicated at maximum power with different exposure times. A comparison of technological and physicochemical properties of the resulting tablets with those of the tablets obtained using the pressing method evidenced significant differences. This suggested that US energy dissipation (mechanical and thermal effects) was the main mechanism which caused the PAR form I tabletability to improve. It was found that the ultrasound–compacted tablets released the drug at a slower rate compared to pure PAR. This technique was shown to be useful for improving tabletability for low-compressible drugs without the need to use a conventional tabletting machine.
|
7 |
Ultrasound Assisted Processing of Solid State Pharmaceuticals. The application of ultrasonic energy in novel solid state pharmaceutical applications, including solvent free co-crystallisation (SFCC) and enhanced compressibilityAlwati, Abdolati A.M. January 2017 (has links)
The objective of this study was to develop a new method for co-crystal preparation which adhered to green chemistry principles, and provided advantages over conventional methods. A novel, solvent-free, high-power ultrasound (US) technique, for preparing co-crystals from binary systems, was chosen as the technology which could fulfil these aims. The application of this technology for solid state co-crystal preparation was explored for ibuprofen-nicotinamide (IBU-NIC), carbamazepine-nicotinamide (CBZ-NIC) and carbamazepine-saccharin (CBZ-SAC) co-crystals. The effect of different additives and processing parameters such as power level, temperature and sonication time on co-crystallisation was investigated. Characterisation was carried out using DSC, PXRD, FTIR, Raman and HPLC. In addition, an NIR prediction model was developed and combined with multivariate analysis (PLS) and chemometric pre-treatments. It was found to be a robust, reliable and rapid method for the determination of co-crystal purity for the IBU-NIC and CBZ-NIC pairs. Co-crystal quantification of US samples helped to optimise the US method. Finally, a model formulation of paracetamol containing 5% and 10% PEG 8000 was ultrasonicated at maximum power with different exposure times. A comparison of technological and physicochemical properties of the resulting tablets with those of the tablets obtained using the pressing method evidenced significant differences. This suggested that US energy dissipation (mechanical and thermal effects) was the main mechanism which caused the PAR form I tabletability to improve. It was found that the ultrasound–compacted tablets released the drug at a slower rate compared to pure PAR. This technique was shown to be useful for improving tabletability for low-compressible drugs without the need to use a conventional tabletting machine.
|
Page generated in 0.0401 seconds