Amorphous Drug Preparation Methods

Rams-Baron, Marzena; Jachowicz, Renata; Болдырева, Е. В.; Zhou, Deliang; Jamróz, Witold; Paluch, Marian

doi:10.1007/978-3-319-72002-9_4

Cited by 2 publications

(3 citation statements)

References 185 publications

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“…The fact that the fine powder of Pz is crystalline is very important for practical applications. While amorphous drugs usually have higher solubility and higher dissolution rates than their crystalline counterparts [ 56 , 57 , 58 , 59 ], they remain metastable. Therefore, the solubility remains higher, only until the transformation into the thermodynamically more stable crystalline form inevitably occurs [ 56 , 60 ].…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2022

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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.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2022

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“…Moreover, this confined water often preserves its influence on mechanochemical transformations even on cryogrinding, when any fluid water gets frozen. 4,[126][127][128][129][130][131][132]…”

Section: Resultsmentioning

confidence: 99%

“…In the past, the majority of efforts were devoted to assess the mobility of amorphous pharmaceuticals, with the glass transition attracting most of the attention. [1][2][3][4] Such initial emphasis on molecular mobility and glass transition was indeed very natural, considering that the most dramatic and obvious result of liquid-to-glass conversion is the increase in viscosity by many orders of magnitude in a relatively narrow temperature interval. In addition, the glass transition temperature (T g ) can be conveniently measured using common laboratory instruments.…”

Section: Introductionmentioning

confidence: 99%

Freezing of Aqueous Solutions and Chemical Stability of Amorphous Pharmaceuticals: Water Clusters Hypothesis

Shalaev

Soper

Zeitler

et al. 2019

Journal of Pharmaceutical Sciences

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Molecular mobility has been traditionally invoked to explain physical and chemical stability of diverse pharmaceutical systems. Although the molecular mobility concept has been credited with creating a scientific basis for stabilization of amorphous pharmaceuticals and biopharmaceuticals, it has become increasingly clear that this approach represents only a partial description of the underlying fundamental principles. An additional mechanism is proposed herein to address 2 key questions: (1) the existence of unfrozen water (i.e., partial or complete freezing inhibition) in aqueous solutions at subzero temperatures and (2) the role of water in the chemical stability of amorphous pharmaceuticals. These apparently distant phenomena are linked via the concept of water clusters. In particular, freezing inhibition is associated with the confinement of water clusters in a solidified matrix of an amorphous solute, with nanoscaled water clusters being observed in aqueous glasses using wide-angle neutron scattering. The chemical instability is suggested to be directly related to the catalysis of proton transfer by water clusters, considering that proton transfer is the key elementary reaction in many chemical processes, including such common reactions as hydrolysis and deamidation.

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Amorphous Drug Preparation Methods

Cited by 2 publications

References 185 publications

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

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

Freezing of Aqueous Solutions and Chemical Stability of Amorphous Pharmaceuticals: Water Clusters Hypothesis

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