Solid State Testing of Inhaled Formulations
Anthony J. Hickey, Sandro R.P. da Rocha in Pharmaceutical Inhalation Aerosol Technology, 2019
Microcalorimetry is very sensitive in measuring the amorphicity of solids. Depending on the compound and testing conditions, amorphicity of less than 1% can be detected (British Pharmacopoeia 2017, European Pharmacopoeia 2017, United States Pharmacopeia 40-National Formulary 35 2017). This technique measures the heat of recrystallization upon exposing the sample to high relative humidity or organic vapor inside a sealed ampule. The mass of the sample and the type of vapour are chosen so that a sharp recrystallization peak can be measured by the microcalorimeter. The amorphous content can be calculated by comparing the area of this peak to that obtained from an amorphous standard (British Pharmacopoeia 2017, European Pharmacopoeia 2017, United States Pharmacopeia 40-National Formulary 35 2017). The recrystallization dynamics are affected by the nature of the solid and its immediate environment. For example, physical mixtures of fully crystalline and amorphous solids will recrystallizing differently to a partially amorphous solid (British Pharmacopoeia 2017, European Pharmacopoeia 2017, United States Pharmacopeia 40-National Formulary 35 2017). This should be noted when choosing standards and comparing data between samples.
Two Dimensional Crystals of the Rhodopseudomonas Viridis Photosynthetic Reaction Center
Hartmut Michel in Crystallization of Membrane Proteins, 1991
Shortly after Michel’s report of the formation of crystals of the reaction center suitable for X-ray analysis,3 we were able to induce purified reaction centers to form two-dimensional crystalline sheets with a high degree of order.7 As reported in that communication, we used the detergent LDAO (N, N-dimethyldodecylamine-N-oxide) at a 1% concentration to solubilize isolated photosynthetic membranes. After binding the detergent-soluble protein fraction to a hydroxylapatite column, the reaction center protein was eluted by a linear salt gradient. Typically, the ratio OD280/OD830 was in the range 2.3 to 2.6, indicating a high degree of purity in the preparation. Aliquots of the reaction center fraction were dialyzed for at least 24 h against 0.3 1 of 0.1 M sodium phosphate buffer containing 0.01% sodium azide, pH 5.3, at 23°C. The protein concentration of the dialysate was in the range of 1 to 2 mg reaction center protein/ml, as judged by the optical density of the reaction center fraction at 280 nm. This particular condition was optimal, although changes in ionic strength (0.01 to 0.3 M sodium phosphate) and pH (pH 5.0 to 6.6) of the dialysis fluid produced useful crystals. Probably most important was the influence of temperature on crystal formation. Initially, the recrystallization experiments were performed at 4°C with sporadic success. Changing the temperature of the dialysis to 23°C produced improved reaction center crystals.
Physicochemical properties of respiratory particles and formulations
Anthony J. Hickey, Heidi M. Mansour in Inhalation Aerosols, 2019
This relationship suggests that the activation enthalpy and entropy are the most essential parameters defining recrystallization time. For example, according to (58,62), for the two structurally related drugs investigated, nifedipine crystallizes much faster than felodipine, despite having very similar Tg values. The Arrhenius dependence Eq. (1.52) applied to data (58) gives the following values of the activation enthalpies around Tg: ΔH* (nifedipine) = 28 kJ/mol; ΔH* (felodipine) = 42 kJ/mol (the difference in these values is also confirmed by the data in [62]). Similar difference can be found by calculating data from reference (62). According to Eq. (1.54), ΔΔH* provides by far the greatest differentiator for the crystallization time ratio (≃6 × 10−3), with the next largest contribution from ΔΔS* (≃6) and smaller contributions from the configurational entropies and temperature, both at about 0.8. The product of all these contributions gives an order of approximately 102 faster crystallization times for nifedipine, which can be confirmed by the experimental values for their induction times (58).
TNP and its analogs: Modulation of IP6K and CYP3A4 inhibition
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Seulgi Lee, Bernie Byeonghoon Park, Hongmok Kwon, Vitchan Kim, Jang Su Jeon, Rowoon Lee, Milan Subedi, Taehyeong Lim, Hyunsoo Ha, Dongju An, Jaehoon Kim, Donghak Kim, Sang Kyum Kim, Seyun Kim, Youngjoo Byun
New purine-based analogs were synthesised from commercial 2,6-dichloropurine in 2 steps as described in Scheme 1. The reaction of 2,6-dichloropurine with substituted benzylamines in DMF in the presence of triethylamine provided the corresponding 6-substitued purine analogs 2–5 in 70–85% yield. Recrystallization from a mixture of ethanol and water afforded compounds 2–5 in high purity (>95%). When aprotic polar solvents such as DMF and DMSO were used, the reaction of compounds 2–5 with mono-substituted benzylamines (4-fluoro, 4-chloro, 4-nitro, and 3-trifluorobenzylamine) was not successful. However, n-butanol as a solvent in combination with sodium tetrafluoroborate (NaBF4) as a reaction facilitator afforded 2,6-disubsituted purine analogs (6–19). When microwave reaction was applied, the reaction time (3 h) was greatly reduced as compared to the conventional reflux condition (30 h).
Ginsenoside Rg3 liposomes regulate tumor microenvironment for the treatment of triple negative breast cancer
Published in Drug Development and Industrial Pharmacy, 2023
Linan Miao, Hao Ma, Tingjun Dong, Chengcheng Zhao, Tingyu Gao, Tianyi Wu, Huan Xu, Jing Zhang
Oxazoline polymers are usually prepared using cationic ring-opening reactions [24]. The electrophilic reagents were used to initiate the reaction, and the nucleophilic reagents were used to terminate the synthesis process, thus obtaining oxazoline polymers with different side-chain groups and different properties [25]. In this study, Boc-NH-PEOz, where the amino group at one end is protected, can be synthesized using Boc-OTS as initiator and potassium hydroxide/methanol solution as terminator [26]. At the other end, the hydroxyl group underwent esterification with CHM to obtain Boc-NH-PEOz-CHMC, which was further deprotected by Boc and coupled with activated FA to get the final product FPC. In the separation and purification process of Boc-OTS, the recrystallization method was selected first. Ethyl acetate was used as the benign solvent to dissolve the precipitate, and n-hexane was used as the poor solvent to precipitate the product. However, there are still impurities in the product purified by recrystallization. Therefore, the column chromatography method was chosen to separate and purify the product.
A facile one-step preparation of Ca10(PO4)6(OH)2/Li-BioMOFs resin nanocomposites with Glycyrrhiza glabra (licorice) root juice as green capping agent and mechanical properties study
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2020
Fahimeh Asadi, Hamid Forootanfar, Mehdi Ranjbar
All of the material, including NaOH, CaCo3 (calcium carbonate, ≥99.0%), H2PO4 powder (96.986 g/mol Merck, reagent-grade), Li2SO4 (lithium sulphate, 99%, Sigma-Aldrich), cetyltrimethylammonium bromide (CTAB, Molar mass: 364.45 g/mol, ≥99.0%, Sigma-Aldrich), 1,3,5-benzenetricarboxylic acid (98%, Sigma-Aldrich), and lecithin as a bio emulsifier were used and received without further purification, purchased from Merck (Darmstadt, Germany). Also, deionised water was provided in the laboratory. The initial process of recrystallization yielded a yellow solution indicating the presence of impurities. Finally, a colourless solution was obtained indicating the purity of the material. XRD as a powerful analysis can be performed to examine nanomaterials’ crystallography. The XRD patterns of the products were recorded with a Rigaku D-max C III, X-ray diffractometer using Ni-filtered Cu-Ka radiation. To examine the morphological properties and particle size distribution, SEM images were obtained with Philips XL-30ESEM equipped with an energy dispersive X-ray spectroscopy (EDX) under the acceleration voltage of 100 kv. TEM images were obtained on a Philips EM208S with an accelerating voltage of 100 kV. The Fourier-transform infra-red spectroscopy (FT-IR spectra) were recorded by a Shimadzu Varian 4300 spectrophotometer in KBr pellets in the range of 400–4000 cm−1. Atomic force microscopy (AFM) images were obtained with a Nano wizard II JPK Made (Germany).
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