Cocrystals by Design: A Rational Coformer Selection Approach for Tackling the API Problems

Pharmaceutics, Год журнала: 2023, Номер 15(4), С. 1161 - 1161

Опубликована: Апрель 6, 2023

Active pharmaceutical ingredients (API) with unfavorable physicochemical properties and stability present a significant challenge during their processing into final dosage forms. Cocrystallization of such APIs suitable coformers is an efficient approach to mitigate the solubility concerns. A considerable number cocrystal-based products are currently being marketed show upward trend. However, improve API by cocrystallization, coformer selection plays paramount role. Selection not only improves drug's but also therapeutic effectiveness reduces side effects. Numerous have been used till date prepare pharmaceutically acceptable cocrystals. The carboxylic acid-based coformers, as fumaric acid, oxalic succinic citric most commonly in products. Carboxylic capable forming hydrogen bond contain smaller carbon chain APIs. This review summarizes role improving APIs, deeply explains utility afore-mentioned cocrystal formation. concludes brief discussion on patentability regulatory issues related

Язык: Английский

---

1,3,4‐Oxadiazole Bridges: A Strategy to Improve Energetics at the Molecular Level

Angewandte Chemie International Edition, Год журнала: 2020, Номер 60(10), С. 5497 - 5504

Опубликована: Дек. 5, 2020

Abstract Many energetic materials synthesized to date have limited applications because of low thermal and/or mechanical stability. This limitation can be overcome by introducing structural modifications such as a bridging group. In this study, series 1,3,4‐oxadiazole‐bridged furazans was prepared. Their structures were confirmed 1 H and 13 C NMR, infrared, elemental, X‐ray crystallographic analyses. The stability, friction sensitivity, impact detonation velocity, pressure evaluated. hydroxylammonium salt 8 has an excellent performance ( D =9101 m s −1 , P =37.9 GPa) insensitive properties (IS=17.4 J, FS=330 N), which show its great potential high‐performance explosive. Using quantum computation crystal structure analysis, the effect introduction 1,3,4‐oxadiazole moiety on molecular reactivity difference between sensitivities stabilities mono‐ bis‐1,3,4‐oxadiazole bridges are considered. synthetic method for systematic study compounds provide theoretical basis future energetics design.

Язык: Английский

---

Energetic materials based on poly furazan and furoxan structures

Chinese Chemical Letters, Год журнала: 2020, Номер 31(9), С. 2375 - 2394

Опубликована: Янв. 13, 2020

Язык: Английский

---

Structure–Performance Relationship in Thermally Stable Energetic Materials: Tunable Physical Properties of Benzopyridotetraazapentalene by Incorporating Amino Groups, Hydrogen Bonding, and π–π Interactions

Crystal Growth & Design, Год журнала: 2020, Номер 20(3), С. 2106 - 2114

Опубликована: Фев. 14, 2020

Structure–performance investigation has become one of those significant trends for energetic materials and crystallography inevitably. Herein, we report two new deriving from a famous thermally stable explosive benzopyridotetraazapentalene, which was first developed by Huynh Hiskey, et al., at Los Alamos National Laboratory. Owing to the incorporation amino groups, these exhibit different amusing physical performance. Understanding their structures, properties, performances, relationship among them is basis rational design materials. Moreover, conjugated systems, density overlap regions indicator analysis also employed necessarily visualizing quantifying covalent noncovalent interactions. It evident that this strategy incorporating groups into increased coplanarity fused ring, owing contribution hydrogen bonding π–π interactions, can further decrease sensitivity. However, found integrity intramolecular -bonding interaction critical factor, affected thermal stability molecules with inserting progressively. notable diamino-substituted compound 8 exhibits comparable (320 °C) HNS, more dense (d: 1.84 g cm–3), higher nitrogen content (37.43%), lower sensitivity (impact sensitivity: 12 J, friction > 360 N), superior HNS. These discoveries effectively assist preparation other promising toward future high-performing energy applications.

Язык: Английский

---

Progress in Energy−Safety Balanced Cocrystallization of Four Commercially Attractive Nitramines

Crystal Growth & Design, Год журнала: 2024, Номер 24(17), С. 7361 - 7388

Опубликована: Авг. 19, 2024

In 2011, cocrystallization of energetic materials became a hot topic and pathway to overcome the energy−safety contradiction; especially for commercially attractive nitramines, it first preference researchers. The present review focuses on energetic−energetic four CL20, HMX, BCHMX, RDX, structural aspects these cocrystals, their influence thermochemical detonation properties. Cocrystallization has proven be crystal engineering technique achieve safety morphological suitability cocrystals (EECCs). Overall, in most cases, impact sensitivities EECCs are decreased, this is phenomenal change; however, needed adjust with properties slightly, negligible if coformer (EMs) properly chosen. There other notable variations morphologies packing crystals, including key such as relatively high density melting point. These changes occur due binding energy, trigger bond length, cohesive energy during cocrystallization. Researchers highly focused nitramines; earlier reported methods lacking selectivity scalability. When comes adoption industrial scale production EECCs, more difficult. We conducted thorough literature survey. Also we discussed about recently developed VPSZ coagglomeration method, which provides huge opportunity tune performance existing easy up level.

Язык: Английский

---

Different Stoichiometric Ratios Realized in Energetic–Energetic Cocrystals Based on CL-20 and 4,5-MDNI: A Smart Strategy to Tune Performance

Crystal Growth & Design, Год журнала: 2020, Номер 20(6), С. 3826 - 3833

Опубликована: Апрель 20, 2020

A new 1:3 CL-20 (2,4,6,8,10,12-hexanitrohexaazaisowurtzitane)/4,5-MDNI (1-methyl-4,5-dinitroimidazole) cocrystal (1) in combination with the previously reported 1:1 CL-20/4,5-MDNI (2) together have been first realized different stoichiometric ratios based on and 4,5-MDNI energetic–energetic cocrystals. Subtle differences intermolecular interactions packing motifs may lead to formations of cocrystals 1 2 by structure comparisons. Moreover, properties (e.g., density, thermal properties, sensitivity, detonation performances) varied significantly under crystal structures. For instance, comprehensive performances (ρ: 1.813 g/cm3; D: 8604 m/s, P: 34.45 GPa; IS: 16 J) were less excellent than those 2, whereas exhibited a velocity superior that LLM-105 (2,6-diamino-3,5-dinitropyrazine-l-oxide, relatively insensitive explosive) low impact sensitivity close LLM-105; thus, act as high-energy explosive. findings offer insights into design preparation energetic other cocrystals, enrich better understanding for provide smart strategy tune performances.

Язык: Английский

---

Melting points of one- and two-component molecular crystals as effective characteristics for rational design of pharmaceutical systems

Acta Crystallographica Section B Structural Science Crystal Engineering and Materials, Год журнала: 2020, Номер 76(4), С. 696 - 706

Опубликована: Июль 21, 2020

Based on the review of literature results database fusion temperatures two-component molecular crystals (1947 co-crystals) and individual components thereof was built up. To improve design co-crystals with predictable melting temperatures, correlation equations connecting points were deduced. These correlations discovered for 18 different stoichiometric compositions. The coefficients analysed, conclusions about main/determinative slave a co-crystal made. comparative analysis composed from same but stoichiometry showed temperature growth when increasing content high-melting component. differences in determined discussed following: (a) monotropic polymorphic forms, (b) composition stoichiometry, (c) based racemates enantiomers. revealed active pharmaceutical ingredients (APIs) co-formers (CFs) more particularly used design. approach an efficacy parameter allowing prediction lower than those compounds developed.

Язык: Английский

---

Improving the Stability of All-Carbon-Nitrated Azoles through Cocrystallization

Crystal Growth & Design, Год журнала: 2022, Номер 22(4), С. 2158 - 2167

Опубликована: Март 10, 2022

All-carbon-nitrated azoles have the advantages of high density and good oxygen balance, but they are rarely suitable for explosives applications due to their fatal deficiencies, such as poor thermal stability, sensitivity, deliquescence. Cocrystallization technology provides a feasible idea revive all-carbon-nitrated in presence flexible structure designability performance adjustability. In this study, three attractive energetic cocrystals 1–3 were synthesized with conjugate triimidazo[1,2-a:1′,2′-c:1″,2″-e][1,3,5]triazine (TT) another azole [5-nitrotetrazole (HNT), 3,5-dinitro-1,2,4-triazole (HDNT), 3,4,5-trinitropyrazole (TNP)], respectively. All existed stably safely under natural conditions exhibited better frictional sensitivity (FS), impact (IS) than pure HNT, HDNT, TNP. Therein, two melting points (Tm) 2 61.9 95.5 °C higher that its decomposition temperature (Td) was 81.2 HDNT. The mechanical 1 (FS = 80 N IS 24 J) significantly improved compared extremely sensitive HNT < 5 J). Moreover, 3 excellent controllable detonation performances (1.703 g cm–3, 6903 m s–1, 18.0 GPa), which 2,4,6-trinitrotoluene. single-crystal analysis theoretical calculation showed formation primarily depended on N–H···N, C–H···N, C–H···O hydrogen bonds NO2···π interaction π–π stacking. stability obviously energetics, attributed combination these strong bond interactions weak π-stacking interactions. Therefore, cocrystallization promising method give "dead" new life.

Язык: Английский

---

Crystal structure and explosive performance of a new CL-20/benzaldehyde cocrystal

Journal of Molecular Structure, Год журнала: 2020, Номер 1215, С. 128267 - 128267

Опубликована: Апрель 14, 2020

Язык: Английский

---

Probing of Neural Networks as a Bridge from Ab Initio Relevant Characteristics to Differential Scanning Calorimetry Measurements of High‐Energy Compounds

physica status solidi (RRL) - Rapid Research Letters, Год журнала: 2021, Номер 16(3)

Опубликована: Июнь 1, 2021

The relationships between the theoretical values calculated using density functional theory and experimental data derived from differential scanning calorimetry of high‐energy organic compounds are studied. number atoms bonds different types their lengths, minimum eigenfrequencies, atomization energies, ionization potentials, electron affinities, frontier orbital energies. amounts releasing heat (the first peaks higher than 1 kJ g −1 ) corresponding temperatures. Neural networks regression, factor, discriminant, cluster analysis applied to find dependencies data. It is found that amount cannot be predicted in general cases, whereas temperature can with a neural network an accuracy ≈30 °C. Cluster discriminant provides way for classification into three groups. Some these groups require particular rules prediction values.

Язык: Английский

---