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The Secondary Drying and the Fate of Organic Solvents for Spray Dried Dispersion Drug Product

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Abstract

Purpose

To understand the mechanisms of secondary drying of spray-dried dispersion (SDD) drug product and establish a model to describe the fate of organic solvents in such a product.

Methods

The experimental approach includes characterization of the SDD particles, drying studies of SDD using an integrated weighing balance and mass spectrometer, and the subsequent generation of the drying curve. The theoretical approach includes the establishment of a Fickian diffusion model.

Results

The kinetics of solvent removal during secondary drying from the lab scale to a bench scale follows Fickian diffusion model. Excellent agreement is obtained between the experimental data and the prediction from the modeling.

Conclusions

The diffusion process is dependent upon temperature. The key to a successful scale up of the secondary drying is to control the drying temperature. The fate of primary solvents including methanol and acetone, and their potential impurity such as benzene can be described by the Fickian diffusion model. A mathematical relationship based upon the ratio of diffusion coefficient was established to predict the benzene concentration from the fate of the primary solvent during the secondary drying process.

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Abbreviations

API:

Active pharmaceutical ingredient

D:

Diffusion coefficient

DSC:

Differential scanning calorimetry

GC:

Gas chromatography

HPMCAS:

Hydroxypropylmethylcellulose (hypromellose) acetate succinate

ICH:

International conference of harmonisation

MS:

Mass spectroscopy

PSD:

Particle size distribution

PVP K30:

Polyvinylpyrrolidone K30

PXRD:

Powder x-ray diffraction

SDD:

Spray dried dispersion

SEM:

Scanning electron microscope

Tg :

Glass transition temperature

αAB :

Relative diffusion rate of solvent A with respect to solvent B

β:

Diffusion parameter

References

  1. Paudel A, Worku Z, Meeus J, Guns S, Mooter GV. Manufacturing of solid dispersions of poorly water soluble drugs by spray drying: formulation and process considerations. Int J Pharm. 2013;453:263–84.

    Article  Google Scholar 

  2. Mooter GVD. The use of amorphous solid dispersions: a formulation strategy to overcome poor solubility and dissolution rate. Drug Discov Today: Technol. 2012;9(2):79–85.

    Article  Google Scholar 

  3. Ray R. Addressing solubility challenges: using effective technology & problem-solving for delivery solutions. Drug Dev Deliv. 2012;12(6):26–8.

    CAS  Google Scholar 

  4. Dobry DE, Settell DM, Baumann JM, Ray RJ, Graham LI, Beyerinck RA. A model-based methodology for spray-drying process development. J Pharm Innov. 2009;4:133–42.

    Article  PubMed Central  PubMed  Google Scholar 

  5. McCabe WL, Smith JC, Harriott P. Unit Operations of Chemical Engineering. Fifth Edition, McGraw-Hill; 1993; 803.

  6. ICH, Impurities: guideline for residue solvents Q3C(R5). ICH; February 2011.

  7. Yue H, Nicholson S, Young J, Hsieh D, Ketner R, Hall R. Sackett J, Bank E, Castoro J, Randazzo M. Development of a control strategy for benzene impurity in HPMCAS-stabilized spray-dried dispersion drug products using a science-based and risk-based approach. Unpublished.

  8. Matteucci S, Yampolskii Y, Freeman BD, Pinnau I. Transport of gases and vapors in glassy and rubbery polymers. In: Yampolskii Y, Pinnau I, Freeman BD. Editors. Materials science of membranes for gas and vapor separation. John Wiley & Sons, Ltd, 2006

  9. Gamble JF, Ferreira AP, DiMemmo L, Martin K, Mathias N, Schild R, et al. Application of imaging based tools for the characterisation of hollow spray dried amorphous dispersion particles. Int J Pharm. 2014;465:210–7.

    Article  CAS  PubMed  Google Scholar 

  10. Vickery RD, Stefanski KJ, Su C-C, Hageman MJ, Vig BS, Betigeri S.Bioavailable compositions of amorphous piperidinyl compounds. Geneva (Switzerland): World Intellectual Property Organization; 2013 Jan. International Publication Number: WO 2013/013114 A1.

  11. Crank J. The Mathematics of Diffusion. 2nd ed. London (England): Claredon Press; 1975.

    Google Scholar 

  12. Vrentas JS, Vrentas CM. Diffusion and Mass Transfer. Florida: Taylor & Francis/CRC; 2013.

    Google Scholar 

  13. Basmadjian D. The Art of Modeling in Science and Engineering. Chapman & Hall/CRC: Florida; 1999.

    Book  Google Scholar 

  14. Sperling LH. Physical polymer science. 3rd ed. New York (USA): Wiley Interscience; 2001.

  15. Dounce SM, Mundy J, Dai HL. Crystallization at the glass transition in super-cooled thin film of methanol, J Chem Physics. 200; 126, 191111.

  16. Duda JL. Molecular diffusion in polymeric systems. Pure Appl Chem. 1985;57(11):1681–90.

    Article  CAS  Google Scholar 

  17. Cussler EL. Diffusion, mass transfer in fluid system. 2nd ed. Cambride (UK): Cambrideg University Press; 1997.

    Google Scholar 

  18. Flanigan EM et al. Silicalite, a new hydrophobic crystalline silica molecular sieve. Nature. 1978;271:512–6.

    Article  Google Scholar 

  19. Cosseron AF et al. Adsorption of solvent organic compounds in pure silica CHA, *BEA, MFI and STT-type zeolite. Microporous Mesoporous Mater. 2013;173:173147–54.

    Article  Google Scholar 

  20. Chandra P, Koros WJ. Sorption and tranport of methanol in poly(ethylene terephthalate). Polymer. 2009;50:236–44.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors are grateful for the Senior Leadership Team and the project team members at Bristol-Myers Squibb Co. for providing support to accomplish this work. The project team members include Kyle Martin, Dr. Neil Mathias, Dr. Balvinder Vig, Lynn DiMemmo, Dr. Steve Wang and Dr. Steven Chan. The technical team members at Bend Research are greatly acknowledged for their generous technical support for secondary drying. Special thanks are given to Mike Ashton at Intertek Pharmaceutical Services (Manchester, UK) for conducting cryogenic scanning electron microscopy.

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Authors and Affiliations

  1. Drug Product Science & Technology, Bristol-Myers Squibb Company, One Squibb Drive, New Brunswick, New Jersey, 08903, USA

    Daniel S. Hsieh & Daniel Roberts

  2. Analytical and Bioanalytical Development, Bristol-Myers Squibb Company, One Squibb Drive, New Brunswick, New Jersey, 08903, USA

    Hongfei Yue

  3. Drug Product Science & Technology, Bristol-Myers Squibb Company, Reeds Lane, Moreton, Merseyside, CH46 1QW, UK

    Sarah J. Nicholson & John F. Gamble

  4. Chemical Development, Bristol-Myers Squibb Company, One Squibb Drive, New Brunswick, NJ, 08903, USA

    Richard Schild & Mark Lindrud

Authors
  1. Daniel S. Hsieh
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  2. Hongfei Yue
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  3. Sarah J. Nicholson
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  4. Daniel Roberts
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  5. Richard Schild
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  6. John F. Gamble
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  7. Mark Lindrud
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Corresponding author

Correspondence to Daniel S. Hsieh.

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Hsieh, D.S., Yue, H., Nicholson, S.J. et al. The Secondary Drying and the Fate of Organic Solvents for Spray Dried Dispersion Drug Product. Pharm Res 32, 1804–1816 (2015). https://doi.org/10.1007/s11095-014-1577-y

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  • DOI: https://doi.org/10.1007/s11095-014-1577-y

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