Use of pure t-butanol as a solvent for freeze-drying: a case study

Ni, Nina; Tesconi, Marc; Tabibi, S. Esmail; Gupta, Shanker; Yalkowsky, Samuel H.

doi:10.1016/s0378-5173(01)00757-8

Cited by 60 publications

(36 citation statements)

References 5 publications

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“…The ideal solvent for freeze drying has the following properties: a high vapor pressure, a melting point either below or slightly above room temperature, a high viscosity, and a low toxicity. It must provide a stable environment for freeze drying and be rapidly and completely removed to produce dry material (Ni et al 2001 ) .…”

Section: Ease Of Lyophilizationmentioning

confidence: 99%

“…1,4-dioxane/water co-solvent was extensively used to make feed solutions for TFF process (Overhoff et al 2007a, b ;DiNunzio et al 2008 ;Yang et al 2008a, b ) , mainly due to its relatively high freezing point and vapor pressure which make the freezing and lyophilization processes easily manageable. These solvents prove benefi cial by reducing the lyophilization time (Ni et al 2001 ) or eliminating the solvent-removal process altogether as some of these solvents sublime at ambient conditions or higher (Tesconi et al 1999 ) . Moreover, they have low biological toxicity and basically no harmful impact to the environment.…”

Section: Ease Of Lyophilizationmentioning

confidence: 99%

See 1 more Smart Citation

Pharmaceutical Cryogenic Technologies

Yang¹,

Owens²,

Williams

2011

Formulating Poorly Water Soluble Drugs

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Poor bioavailability associated with poorly water-soluble compounds remains a challenging issue in drug development. Particle engineering may be used to improve the physicochemical properties of poorly water-soluble compounds, thereby enhancing the bioavailability. Cryogenic technologies, including spray freeze drying (SFD), spray freezing into liquid (SFL), and thin fi lm freezing (TFF), are "bottom-up" precipitation processes to generate amorphous nanostructured aggregates with signifi cantly enlarged surface area, higher dissolution rates, and supersaturation, via rapidly inducing nucleation followed by particle growth arrest through stabilization via polymers and solidifi cation of the solvent. This chapter provides detailed description of each cryogenic process, formulation guidelines, and characterization analyses. Finally, examples of cryogenically engineered drug compositions with improved in vitro and in vivo macroscopic performance are provided to illustrate the potential benefi ts of cryogenic technologies, especially TFF.

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Section: Ease Of Lyophilizationmentioning

confidence: 99%

Section: Ease Of Lyophilizationmentioning

confidence: 99%

Pharmaceutical Cryogenic Technologies

Yang¹,

Owens²,

Williams

2011

Formulating Poorly Water Soluble Drugs

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“…9 TBA is one of the organic solvents that has been used often in freeze drying. [9][10][11][12][13][14][15] The benefits of TBA are shorter freeze-drying times and significantly higher specific surface areas of freeze-dried products.…”

Section: Solubility and Stability Of Eo-9mentioning

confidence: 99%

Development of a bladder instillation of the indoloquinone anticancer agent EO-9 using tert-butyl alcohol as lyophilization vehicle

et al. 2007

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The purpose of this research was to develop a stable bladder instillation of EO-9 for the treatment of superficial bladder cancer. First, stability and dissolution studies were performed. Subsequently, the freeze-drying process was optimized by determination of the freeze-drying characteristics of the selected cosolvent/water system and differential scanning calorimetry analysis of the formulation solution. Furthermore, the influence of the freeze-drying process on crystallinity and morphology of the freeze-dried product was determined with x-ray diffraction analysis and scanning electron microscopy, respectively. Subsequently, a reconstitution solution was developed. This study revealed that tert-butyl alcohol (TBA) can be used to both dramatically improve the solubility and stability of EO-9 and to shorten the freeze-drying cycle by increasing the sublimation rate. During freeze drying, 3 TBA crystals were found: TBA hydrate-ice crystals, crystals of TBA hydrate, and a third crystal, probably composed of TBA hydrate crystals containing~90% to 95% TBA. Furthermore, it was shown that crystallization of TBA hydrate was inhibited in the presence of both sodium bicarbonate (NaHCO 3 ) and mannitol. Addition of an annealing step resulted in a minor increase in the crystallinity of the freeze-dried product and formation of the δ-polymorph of mannitol. A stable bladder instillation was obtained after reconstitution of the freeze-dried product (containing 8 mg of EO-9, 20 mg of NaHCO 3 , and 50 mg of mannitol per vial) to 20 mL with a reconstitution solution composed of propylene glycol/water for injection (WfI)/NaHCO 3 /sodium edetate 60%/40%/2%/0.02% vol/ vol/wt/wt, followed by dilution with WfI to a final volume of 40 mL.

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“…Tertiary butyl alcohol (TBA) is one of the most popular solvents used in freeze-dried formulations. Freezing and freeze-drying behavior of ingredients in solutions containing TBA has been evaluated (8)(9)(10)(11). Ni et al have demonstrated that TBA improved the stability of an antitumor drug by creating needle-shaped crystals during the freeze-drying process (8).…”

Section: Introductionmentioning

confidence: 99%

“…Freezing and freeze-drying behavior of ingredients in solutions containing TBA has been evaluated (8)(9)(10)(11). Ni et al have demonstrated that TBA improved the stability of an antitumor drug by creating needle-shaped crystals during the freeze-drying process (8). Telang et al studied the effect of TBA on the crystallization and stability of cephalothin sodium (9).…”

Section: Introductionmentioning

confidence: 99%