Pharma Engineering & Design 2023

Lyophilization
Sulastari Cahyani
(22/498866/PFA/02208)

Dosen Pengampu :
Dr. Eng.apt. Khadijah.,M.Si.
 Pendahuluan

Lyophilization Konsep

Aplikasi
 Lyophilization Pendahuluan
• Lyophilization atau Freeze drying
adalah proses pengeringan di mana
air menyublim setelah dibekukan.

• Cocok untuk proses pengeringan

pada pembuatan obat-obatan dan
biologi tertentu yang termolabil
atau tidak stabil dalam larutan
berair untuk penyimpanan yang
lama, tetapi stabil dalam keadaan
kering.

• Istilah "liofilisasi" menggambarkan

proses untuk menghasilkan produk
yang "menyukai keadaan kering"

Kommineni, N., Butreddy, A., Sainaga Jyothi, V. G. S., & Angsantikul, P. 2022. Freeze-drying for the preservation of
immunoengineering products. https://doi.org/10.1016/j.isci application of freeze-drying for immunoengineering technologies and products
Lyophilization Konsep

• Sublimasi
terjadi jika suhu
dan tekanan
berada dibawah
triple point

Gaidhani, K. A., Harwalkar, M., Bhambere, D., & Nirgude, P. S. 2015. LYOPHILIZATION / FREEZE DRYING-A REVIEW.
Kunal et al. World Journal of Pharmaceutical Research World Journal of Pharmaceutical Research SJIF Impact Factor 5, 4(8),
517. www.wjpr.net
 Lyophilization Konsep

Freezing

Primary
Drying

Secondary
Drying

Kommineni, N., Butreddy, A., Sainaga Jyothi, V. G. S., & Angsantikul, P. 2022. Freeze-drying for the preservation of
immunoengineering products. https://doi.org/10.1016/j.isci
Freeze-drying process
Lyophilization Konsep

Freezing

Primary
Drying

Secondary
Drying

Rey, L., & May, J. C. (n.d.). Freeze Drying/Lyophilization of Pharmaceutical and Biological Products.
Lyophilization Konsep

https://youtu.be/NIoP2N4TeqQ
Freeze-drying process
 Lyophilization Konsep

Cryoprotectants

Kommineni, N., Butreddy, A., Sainaga Jyothi, V. G. S., & Angsantikul, P. 2022. Freeze-drying for the preservation of
immunoengineering products. https://doi.org/10.1016/j.isci
Lyophilization Konsep

Bjelošević, M., Zvonar Pobirk, A., Planinšek, O., & Ahlin Grabnar, P. 2020. Excipients in freeze-dried biopharmaceuticals:
Contributions toward formulation stability and lyophilisation cycle optimisation. In International Journal of
Pharmaceutics (Vol. 576). Elsevier B.V. https://doi.org/10.1016/j.ijpharm.2020.119029
Lyophilization Konsep

Bjelošević, M., Zvonar Pobirk, A., Planinšek, O., & Ahlin Grabnar, P. 2020. Excipients in freeze-dried biopharmaceuticals:
Contributions toward formulation stability and lyophilisation cycle optimisation. In International Journal of
Pharmaceutics (Vol. 576). Elsevier B.V. https://doi.org/10.1016/j.ijpharm.2020.119029
Lyophilization to Increasing Solubility Aplikasi

Tran, P., Pyo, Y. C., Kim, D. H., Lee, S. E., Kim, J. K., & Park, J. S. 2019. Overview of the manufacturing methods of
solid dispersion technology for improving the solubility of poorly water-soluble drugs and application to anticancer
drugs. In Pharmaceutics (Vol. 11, Issue 3). MDPI AG. https://doi.org/10.3390/pharmaceutics11030132
Lyophilization to Increasing Solubility Aplikasi

Tran, P., Pyo, Y. C., Kim, D. H., Lee, S. E., Kim, J. K., & Park, J. S. 2019. Overview of the manufacturing methods of solid dispersion technology for improving the
solubility of poorly water-soluble drugs and application to anticancer drugs. In Pharmaceutics (Vol. 11, Issue 3). MDPI AG.
https://doi.org/10.3390/pharmaceutics11030132
Lyophilization to Increasing Solubility Aplikasi

Poloxamer 188 Poloxamer 235

Polimer hidrofilik = Surfaktan a= POE, Poly (oxyethylene)

b= PPO, Poly (oxypropylene)
Anticancer, BCS IV
Freeze drying

Song, C. K., Yoon, I. S., & Kim, D. D. 2016. Poloxamer-based solid dispersions for oral delivery of docetaxel: Differential
effects of F68 and P85 on oral docetaxel bioavailability. International Journal of Pharmaceutics, 507(1–2), 102–108.
https://doi.org/10.1016/j.ijpharm.2016.05.002
Lyophilization to Increasing Solubility Aplikasi

Freeze drying

Freezing Dryng Product

Etanol+docetaxel+F68/P85 –135 C 20 C

Song, C. K., Yoon, I. S., & Kim, D. D. 2016. Poloxamer-based solid dispersions for oral delivery of docetaxel: Differential
effects of F68 and P85 on oral docetaxel bioavailability. International Journal of Pharmaceutics, 507(1–2), 102–108.
https://doi.org/10.1016/j.ijpharm.2016.05.002
Lyophilization to Increasing Solubility Aplikasi
Lyophilization to Increasing Solubility Aplikasi
Lyophilization to Increasing Solubility Aplikasi
o Dispersi padat docetaxel hanya dengan pembawa
F68 (Poloxamer 188) secara signifikan
meningkatkan disolusi tetapi tidak meningkatkan
permeasi docetaxel ke usus, sehingga hanya
sedikit meningkatkan bioavailabilitas oral
(peningkatan 1,39 kali lipat).
o Akan tetapi dispersi padat docetaxel dengan
kombinasi pembawa F68(Poloxamer 188) dan
P85( Poloxamer 235) secara signifikan
meningkatkan disolusi dan permeasi docetaxel di
usus, terjadi peningkatan bioavailabilitas oral
sebesar 2,97 kali lipat.
o Freeze drying menghasilkan produk akhir dengan
kelarutan yang lebih tinggi dibandingkan senyawa
murni dikarenakan menghasilkan porositas serta
luas permukaan yang besar
Lyophilization Kesimpulan

Kelebihan Kekurangan
Cocok untuk senyawa Relatif mahal
termolabil
Penyimpanan relatif Lama
lama
Relatif lebih stabil Mudah terdegredasi
Menghasilkan Kurang cocok untuk
peningkatan kelarutan produk yang tidak tahan
pada suhu rendah
Cocok untuk produk
biologi steril
  Bjelošević, M., Zvonar Pobirk, A., Planinšek, O., & Ahlin Grabnar, P. 2020. Excipients in freeze-
dried biopharmaceuticals: Contributions toward formulation stability and lyophilisation cycle
optimisation. In International Journal of Pharmaceutics (Vol. 576). Elsevier B.V.
https://doi.org/10.1016/j.ijpharm.2020.119029
 Tran, P., Pyo, Y. C., Kim, D. H., Lee, S. E., Kim, J. K., & Park, J. S. 2019. Overview of the
manufacturing methods of solid dispersion technology for improving the solubility of poorly
water-soluble drugs and application to anticancer drugs. In Pharmaceutics (Vol. 11, Issue 3).
MDPI AG. https://doi.org/10.3390/pharmaceutics11030132
 Song, C. K., Yoon, I. S., & Kim, D. D. 2016. Poloxamer-based solid dispersions for oral delivery of
docetaxel: Differential effects of F68 and P85 on oral docetaxel bioavailability. International
Journal of Pharmaceutics, 507(1–2), 102–108. https://doi.org/10.1016/j.ijpharm.2016.05.002
Terimakasih...  Kommineni, N., Butreddy, A., Sainaga Jyothi, V. G. S., & Angsantikul, P. 2022. Freeze-drying for
the preservation of immunoengineering products. https://doi.org/10.1016/j.isci
 Rey, L., & May, J. C. (n.d.). Freeze Drying/Lyophilization of Pharmaceutical and Biological
Products.
 Gaidhani, K. A., Harwalkar, M., Bhambere, D., & Nirgude, P. S. 2015. Lyophilization / Freeze
Drying-a Review. Kunal et al. World Journal of Pharmaceutical Research World Journal of
Pharmaceutical Research SJIF Impact Factor 5, 4(8), 517. www.wjpr.net

 You can do it!