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

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Diffusion and Flux Improvement of Drugs through Complexation

Molecular Pharmaceutics, Год журнала: 2023, Номер 20(5), С. 2293 - 2316

Опубликована: Март 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

Язык: Английский

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On the Road to Cocrystal Prediction: A Screening Study for the Validation of In Silico Methods

Crystal Growth & Design, Год журнала: 2024, Номер 24(13), С. 5486 - 5493

Опубликована: Июнь 20, 2024

The pharmaceutical industry is increasingly exploring cocrystals as a solution to provide improved material properties for otherwise intractable active ingredients (APIs). Researchers have attempted streamline the experimental process of screening by developing in silico predictive tools. These tools use intermolecular interactions, primarily hydrogen bonding, well other molecular descriptors quickly assess likelihood cocrystal formation between an API and set small-molecule coformers. We developed web-based application using three such help us prioritize against library nearly 300 individual In order validate our algorithms, molecules from compound were screened, experimentally with application, subset 40 Here, we present design app, work used its predictions, relative success techniques.

Язык: Английский

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Expanding the Crystal Structure Landscape of Pravastatin Complexes: Tuning Solubility, Diffusion, and Pharmacokinetics

Crystal Growth & Design, Год журнала: 2024, Номер 24(12), С. 5309 - 5323

Опубликована: Июнь 1, 2024

Pravastatin (PRV), a lipid-lowering medication, is prescribed to treat cardiovascular disease and dyslipidemia. Due its low permeability high solubility, the biopharmaceutics classification system (BCS) class III drug exhibits poor bioavailability. To overcome bottlenecks of PRV, novel complexes with Zn Cu along zwitterionic cocrystal l-proline (PRO) were synthesized. These new solid forms characterized by SC-XRD, PXRD, DSC, TGA, FT-IR, DVS, SEM images. Rietveld refinement was used obtain 3D coordinates PRV–Na–PRO ionic hydrate from high-resolution PXRD data. PRV–Cu obtained substituting PRV sodium salt Cu/Zn metal. In hydrate, each Na metal coordinated carboxylates (2) PRO (1) three water molecules result in an octahedron geometry. two carboxylate anions molecules, forming square pyramidal The PRV–Zn complex maintains octahedral geometry using four coordination molecules. exhibited higher solubility (1.7-fold) diffusion profile (1.1-fold) compared commercial PRV–Na whereas PRV–Cu/Zn showed controlled release. Surprisingly, enhanced peak plasma concentration Cmax (50 fold) AUC (14.4 during pharmacokinetics study rats. stability supported ground-state optimization energy calculations. Unlike moisture-sensitive PRV–Zn/Cu far superior moisture may offer extended On other hand, significantly improved bioavailability can be commercialized following proper formulation that offers stability.

Язык: Английский

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Study of chemical reactivity and molecular interactions of the hydrochlorothiazide-4-aminobenzoic acid cocrystal using spectroscopic and quantum chemical approaches

Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy, Год журнала: 2024, Номер 324, С. 124960 - 124960

Опубликована: Авг. 11, 2024

Язык: Английский

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Tuning Caco-2 permeability by cocrystallization: Insights from molecular dynamics simulation

International Journal of Pharmaceutics, Год журнала: 2023, Номер 650, С. 123666 - 123666

Опубликована: Дек. 7, 2023

Язык: Английский

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Development of direct compression Acetazolamide tablet with improved bioavailability in healthy human volunteers enabled by cocrystallization with p-Aminobenzoic acid

International Journal of Pharmaceutics, Год журнала: 2024, Номер 652, С. 123793 - 123793

Опубликована: Янв. 7, 2024

Язык: Английский

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Synthesis of naringenin-betaine cocrystal by gas antisolvent technique and cell models for in vitro permeation studies

Journal of Drug Delivery Science and Technology, Год журнала: 2024, Номер 96, С. 105671 - 105671

Опубликована: Апрель 15, 2024

Язык: Английский

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Mechanosynthesis of Stable Salt Hydrates of Allopurinol with Enhanced Dissolution, Diffusion, and Pharmacokinetics

ACS Omega, Год журнала: 2023, Номер 8(37), С. 34120 - 34133

Опубликована: Сен. 7, 2023

Allopurinol (ALO) is a medication that treats gout and kidney stones by lowering uric acid synthesis in the blood. The biopharmaceutics classification system (BCS) IV drug exhibits poor aqueous solubility, permeability, bioavailability. To overcome bottlenecks of ALO, salts with maleic (MLE) oxalic (OXA) were synthesized using solvent-assisted grinding method. novel multicomponent solids characterized PXRD, DSC, TGA, FT-IR, SEM images. crystal structures these variable stoichiometry obtained Rietveld refinement from high-resolution PXRD data. proton dicarboxylic transferred to most basic pyrimidine "N" ALO. N-H···N hydrogen-bonded ALO homodimer replaced N

Язык: Английский

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Mechanistic Insight in Permeability through Different Membranes in the Presence of Pharmaceutical Excipients: A Case of Model Hydrophobic Carbamazepine

Pharmaceutics, Год журнала: 2024, Номер 16(2), С. 184 - 184

Опубликована: Янв. 28, 2024

The present study reports the effects of two pharmaceutical excipients differing natures—non-ionic surfactant pluronic F127 (F127) and anionic sulfobutylether-β-cyclodextrin (SBE-β-CD)—on permeation model compound, carbamazepine (CBZ). permeability coefficients CBZ at three concentrations were measured through different artificial barriers: hydrophilic cellulose membrane (RC) lipophilic polydimethylsiloxane–polycarbonate (PDS). equilibrium solubility in SBE-β-CD solutions was determined. micellization, complexation, aggregation tendencies investigated. Systemically increasing reduction upon excipients’ concentration growth revealed. quantitative evaluation carried out using a Pratio parameter, quasi-equilibrium mathematical mass transport model, correction for free drug (“true” values). results revealed mutual influence excipient properties nature on variations.

Язык: Английский

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