CrystEngComm, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
A solid-state study of the weak non-covalent interactions in p -C 6 F 4 Cl 2 and C 5 reveals complex phase behaviour latter. The disordered form II is isomorphous to crystal structure .
Language: Английский
International Journal of Pharmaceutics X, Journal Year: 2024, Volume and Issue: 7, P. 100259 - 100259
Published: June 1, 2024
Forty-eight (48) drug products (DPs) containing amorphous solid dispersions (ASDs) have been approved by the U.S. Food and Drug Administration in 12-year period between 2012 2023. These DPs comprise 36 unique drugs. Ten (10) therapeutic categories are represented, with most antiviral antineoplastic agents. The common ASD polymers copovidone (49%) hypromellose acetate succinate (30%), while spray drying (54%) hot melt extrusion (35%) utilized manufacturing processes to prepare product intermediate (DPI). Tablet dosage forms common, several capsule available. Line extensions of based on flexible oral solids powders for suspension which provide patient-centric dosing pediatric other patient populations. trends use excipients film coating types discussed. Eighteen (18) fixed-dose combinations, some contain a mixture crystalline dose/unit ranging from <5 mg up 300 mg, majority being ≤100 mg/unit. This review details aspects DPI DP formulation ASDs, as well related category, dose, patient-centricity.
Language: Английский
Citations
35
Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(1), P. 94 - 94
Published: Jan. 1, 2022
Hesperetin (HES) is a key biological active ingredient in citrus peels, and one of the natural flavonoids that attract attention researchers due to its numerous therapeutic bioactivities have been identified vitro. As bioenhancer, piperine (PIP) can effectively improve absorption insoluble drugs vivo. In present study, cocrystal HES PIP was successfully obtained through solution crystallization. The single-crystal structure illustrated comprehensive characterization conducted. formed by two drug molecules at molar ratio 1:1, which contained O-H-O hydrogen bonds between carbonyl ether oxygen phenolic hydroxyl group HES. addition, solubility experiment performed on powder simulated gastrointestinal fluid, result revealed improves dissolution behavior compared with pure substance. Furthermore, HES's bioavailability six times higher than pristine drugs. These results may provide an efficient oral formulation for
Language: Английский
Citations
40
Molecular Pharmaceutics, Journal Year: 2023, Volume and Issue: 20(5), P. 2293 - 2316
Published: March 28, 2023
Improving the solubility and permeability of drugs via cocrystallization is an important theme in crystal engineering with practical applications for discovery development high bioavailability medicines. The past decade has witnessed a surge publications on pharmaceutical cocrystals/salts to improve Biopharmaceutics Classification System (BCS) class IV drugs. In this review article, reader introduced fundamentals drug mechanisms then examples cocrystals salts designed enhance diffusion are presented, order understand different structural factors that modulate flux transport across semipermeable membrane. Broadly, two main phenomena can be summarized from 50 or so examples: (1) heterosynthons hydrogen-bonded drug–coformer aggregates survive long enough experimental media such drug, which present concentration due supersaturation, exhibits higher (2) coformer cocrystal able reduce transepithelial electrical resistance (TEER) values lipid monolayers, impairs their tight junctions, facilitates passage its diffusion/permeability. medicinal chemistry literature recapitulated idea these principles may utilized de novo design coformers synthesis improved-performance cocrystals. Enhancing without changing molecular structure supramolecular complexes will address poor challenge majority BCS II
Language: Английский
Citations
32
CrystEngComm, Journal Year: 2024, Volume and Issue: 26(11), P. 1505 - 1526
Published: Jan. 1, 2024
A holistic understanding of reaction kinetics, the presence catalysts, and annealing conditions can advance accelerate screening elusive cocrystals, expediting development novel drug cocrystals for future clinical use.
Language: Английский
Citations
12
CrystEngComm, Journal Year: 2022, Volume and Issue: 24(17), P. 3122 - 3135
Published: Jan. 1, 2022
Antisolvent crystallization is a significant unit operation in the pharmaceutical industry, especially drug crystal property optimization.
Language: Английский
Citations
31
Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(2), P. 300 - 300
Published: Jan. 27, 2022
Formulating pharmaceutical cocrystals as inhalable dosage forms represents a unique niche in effective management of respiratory infections. Favipiravir, broad-spectrum antiviral drug with potential pharmacological activity against SARS-CoV-2, exhibits low aqueous solubility. An ultra-high oral dose is essential, causing patient compliance. This study reports Quality-by-Design (QbD)-guided development carrier-free dry powder formulation containing 1:1 favipiravir–theophylline (FAV-THP) cocrystal via spray drying, which may provide an alternative treatment strategy for individuals concomitant influenza infections and chronic obstructive pulmonary disease/asthma. The formation was confirmed by single crystal X-ray diffraction, the construction temperature–composition phase diagram. A three-factor, two-level, full factorial design employed to produce optimized impact critical processing parameters on resulting median mass aerodynamic diameter (MMAD), fine particle fraction (FPF), crystallinity spray-dried FAV-THP cocrystal. In general, lower solute concentration feed pump rate resulted smaller MMAD higher FPF. (F1) demonstrated 2.93 μm FPF 79.3%, suitable deep lung delivery no vitro cytotoxicity observed A549 cells.
Language: Английский
Citations
30
Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(3), P. 836 - 836
Published: March 3, 2023
In this study, the existing set of carbamazepine (CBZ) cocrystals was extended through successful combination drug with positional isomers acetamidobenzoic acid. The structural and energetic features CBZ 3- 4-acetamidobenzoic acids were elucidated via single-crystal X-ray diffraction followed by QTAIMC analysis. ability three fundamentally different virtual screening methods to predict correct cocrystallization outcome for assessed based on new experimental results obtained in study data available literature. It found that hydrogen bond propensity model performed worst distinguishing positive negative experiments 87 coformers, attaining an accuracy value lower than random guessing. method utilizes molecular electrostatic potential maps machine learning approach named CCGNet exhibited comparable terms prediction metrics, albeit latter resulted superior specificity overall while requiring no time-consuming DFT computations. addition, formation thermodynamic parameters newly evaluated using temperature dependences Gibbs energy. reactions between selected coformers be enthalpy-driven, entropy being statistically from zero. observed difference dissolution behavior aqueous media thought caused variations their stability.
Language: Английский
Citations
22
Journal of Drug Delivery Science and Technology, Journal Year: 2023, Volume and Issue: 86, P. 104746 - 104746
Published: July 7, 2023
Binary co-amorphous systems (CAMS) are a type of solid dispersion containing an active pharmaceutical ingredient (API) and small molecule excipients. The properties these substances make them novel very demanding aspect research because they improve solubility, physical stability, bioavailability in poorly soluble drugs comparison to their pure crystal or amorphous counterparts. CAMS may however not satisfy all criteria related dissolution, recrystallization prevention, stability. As result, ternary incorporating third offer several advantages terms stability drug solubility. Similarly, the context (ASD) drug's solubility over binary dispersions. During this review, we summarize recent findings regarding CAMS, (TSD) CAMS. Recent advances preparation, mechanism stabilization, in-vitro in-vivo performances also discussed along with final dosage forms.
Language: Английский
Citations
21
Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(6), P. 1747 - 1747
Published: June 15, 2023
Polymorphism is a common phenomenon among single- and multicomponent molecular crystals that has significant impact on the contemporary drug development process. A new polymorphic form of carbamazepine (CBZ) cocrystal with methylparaben (MePRB) in 1:1 molar ratio as well drug's channel-like containing highly disordered coformer molecules have been obtained characterized this work using various analytical methods, including thermal analysis, Raman spectroscopy, single-crystal high-resolution synchrotron powder X-ray diffraction. Structural analysis solid forms revealed close resemblance between novel II previously reported I [CBZ + MePRB] (1:1) terms hydrogen bond networks overall packing arrangements. The was found to belong distinct family isostructural CBZ cocrystals coformers similar size shape. Form appeared be related by monotropic relationship, being proven thermodynamically more stable phase. dissolution performance both polymorphs aqueous media significantly enhanced when compared parent CBZ. However, considering superior thermodynamic stability consistent profile, discovered seems promising reliable for further pharmaceutical development.
Language: Английский
Citations
20
International Journal of Pharmaceutics, Journal Year: 2024, Volume and Issue: 653, P. 123896 - 123896
Published: Feb. 10, 2024
Language: Английский
Citations
8