Clathrate Hydrates of Organic Solvents as Auxiliary Intermediates in Pharmaceutical Research and Development: Improving Dissolution Behaviour of a New Anti-Tuberculosis Drug, Perchlozon

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Clathrate Hydrates of Organic Solvents as Auxiliary Intermediates in Pharmaceutical Research and Development: Improving Dissolution Behaviour of a New Anti-Tuberculosis Drug, Perchlozon. / Ogienko, Andrey G.; Myz, Svetlana A.; Nefedov, Andrey A. et al.

In: Pharmaceutics, Vol. 14, No. 3, 495, 03.2022.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{082518c7594f4d4095ad936ce2f6a42b,

title = "Clathrate Hydrates of Organic Solvents as Auxiliary Intermediates in Pharmaceutical Research and Development: Improving Dissolution Behaviour of a New Anti-Tuberculosis Drug, Perchlozon",

abstract = "There is an urgent need for new drugs to overcome the challenge of the ever-growing drug resistance towards tuberculosis. A new, highly efficient anti-tuberculosis drug, Perchlozone (thioureidoiminomethylpyridinium perchlorate, Pz), is only available in an oral dosage form, though injectable forms and inhalation solutions could be better alternatives, offering higher bioavailability. To produce such forms, nano-and micro-particles of APIs would need to be prepared as dispersions with carriers. We use this case study to illustrate the principles of selecting solvents and excipients when preparing such formulations. We justify the choice of water–THF (19.1 wt % THF) as solvent and mannitol as carrier to prepare formulations of Pz—a poorly soluble compound—that are suitable for injection or inhalation. The formulations could be prepared by conventional freeze-drying in vials, making the proposed method suitable for industrial scaling. A similar strategy for selecting the organic solvent and the excipient can be applied to other compounds with low water solubility.",

keywords = "Anti-tuberculosis drugs, Clathrate hydrates, Formulations for inhalation, Formulations for injections, Freeze-drying",

author = "Ogienko, {Andrey G.} and Myz, {Svetlana A.} and Nefedov, {Andrey A.} and Ogienko, {Anna A.} and Adamova, {Tatyana P.} and Voronkova, {Olga M.} and Amosova, {Svetlana V.} and Trofimov, {Boris A.} and Boldyrev, {Vladimir V.} and Boldyreva, {Elena V.}",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = mar,

doi = "10.3390/pharmaceutics14030495",

language = "English",

volume = "14",

journal = "Pharmaceutics",

issn = "1999-4923",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "3",

}

RIS

TY - JOUR

T1 - Clathrate Hydrates of Organic Solvents as Auxiliary Intermediates in Pharmaceutical Research and Development: Improving Dissolution Behaviour of a New Anti-Tuberculosis Drug, Perchlozon

AU - Ogienko, Andrey G.

AU - Myz, Svetlana A.

AU - Nefedov, Andrey A.

AU - Ogienko, Anna A.

AU - Adamova, Tatyana P.

AU - Voronkova, Olga M.

AU - Amosova, Svetlana V.

AU - Trofimov, Boris A.

AU - Boldyrev, Vladimir V.

AU - Boldyreva, Elena V.

PY - 2022/3

Y1 - 2022/3

N2 - There is an urgent need for new drugs to overcome the challenge of the ever-growing drug resistance towards tuberculosis. A new, highly efficient anti-tuberculosis drug, Perchlozone (thioureidoiminomethylpyridinium perchlorate, Pz), is only available in an oral dosage form, though injectable forms and inhalation solutions could be better alternatives, offering higher bioavailability. To produce such forms, nano-and micro-particles of APIs would need to be prepared as dispersions with carriers. We use this case study to illustrate the principles of selecting solvents and excipients when preparing such formulations. We justify the choice of water–THF (19.1 wt % THF) as solvent and mannitol as carrier to prepare formulations of Pz—a poorly soluble compound—that are suitable for injection or inhalation. The formulations could be prepared by conventional freeze-drying in vials, making the proposed method suitable for industrial scaling. A similar strategy for selecting the organic solvent and the excipient can be applied to other compounds with low water solubility.

AB - There is an urgent need for new drugs to overcome the challenge of the ever-growing drug resistance towards tuberculosis. A new, highly efficient anti-tuberculosis drug, Perchlozone (thioureidoiminomethylpyridinium perchlorate, Pz), is only available in an oral dosage form, though injectable forms and inhalation solutions could be better alternatives, offering higher bioavailability. To produce such forms, nano-and micro-particles of APIs would need to be prepared as dispersions with carriers. We use this case study to illustrate the principles of selecting solvents and excipients when preparing such formulations. We justify the choice of water–THF (19.1 wt % THF) as solvent and mannitol as carrier to prepare formulations of Pz—a poorly soluble compound—that are suitable for injection or inhalation. The formulations could be prepared by conventional freeze-drying in vials, making the proposed method suitable for industrial scaling. A similar strategy for selecting the organic solvent and the excipient can be applied to other compounds with low water solubility.

KW - Anti-tuberculosis drugs

KW - Clathrate hydrates

KW - Formulations for inhalation

KW - Formulations for injections

KW - Freeze-drying

UR - http://www.scopus.com/inward/record.url?scp=85125641787&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/aaa32b37-d028-3b4c-8eb7-a0b5020112e4/

U2 - 10.3390/pharmaceutics14030495

DO - 10.3390/pharmaceutics14030495

M3 - Article

C2 - 35335870

AN - SCOPUS:85125641787

VL - 14

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 3

M1 - 495

ER -

ID: 35611619