Quality by Design Approach in Liposomal Formulations: Robust Product Development

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2023 Jan 8

PMID 36615205

Authors

Walhan Alshaer

Hamdi Nsairat

Zainab Lafi

Omar M Hourani

Abdulfattah Al-Kadash

Ezaldeen Esawi

Alaaldin M Alkilany

Affiliations

Soon will be listed here.

Abstract

Nanomedicine is an emerging field with continuous growth and differentiation. Liposomal formulations are a major platform in nanomedicine, with more than fifteen FDA-approved liposomal products in the market. However, as is the case for other types of nanoparticle-based delivery systems, liposomal formulations and manufacturing is intrinsically complex and associated with a set of dependent and independent variables, rendering experiential optimization a tedious process in general. Quality by design (QbD) is a powerful approach that can be applied in such complex systems to facilitate product development and ensure reproducible manufacturing processes, which are an essential pre-requisite for efficient and safe therapeutics. Input variables (related to materials, processes and experiment design) and the quality attributes for the final liposomal product should follow a systematic and planned experimental design to identify critical variables and optimal formulations/processes, where these elements are subjected to risk assessment. This review discusses the current practices that employ QbD in developing liposomal-based nano-pharmaceuticals.

Citing Articles

How Advanced are Self-Assembled Nanomaterials for Targeted Drug Delivery? A Comprehensive Review of the Literature.

Nsairat H, Lafi Z, Al-Najjar B, Al-Samydai A, Saqallah F, El-Tanani M Int J Nanomedicine. 2025; 20:2133-2161.

PMID: 39990285 PMC: 11847455. DOI: 10.2147/IJN.S490444.

Potentiation of Doxorubicin Cytotoxicity Utilizing Clarithromycin Loaded-PEGylated Liposomes.

Alfreahat I, Nsairat H, Aldeeb I, Al-Samydai A, Alshaer W Technol Cancer Res Treat. 2025; 24:15330338241312561.

PMID: 39865928 PMC: 11770720. DOI: 10.1177/15330338241312561.

Liposomal Formulations: A Recent Update.

Agrawal S, Baliga V, Londhe V Pharmaceutics. 2025; 17(1).

PMID: 39861685 PMC: 11769406. DOI: 10.3390/pharmaceutics17010036.

Enhancing Acute Migraine Treatment: Exploring Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for the Nose-to-Brain Route.

Torres J, Silva R, Farias G, Sousa Lobo J, Ferreira D, Silva A Pharmaceutics. 2024; 16(10).

PMID: 39458626 PMC: 11510892. DOI: 10.3390/pharmaceutics16101297.

Review on PLGA Polymer Based Nanoparticles with Antimicrobial Properties and Their Application in Various Medical Conditions or Infections.

Shakya A, Al-Sulaibi M, Naik R, Nsairat H, Suboh S, Abulaila A Polymers (Basel). 2023; 15(17).

PMID: 37688223 PMC: 10490122. DOI: 10.3390/polym15173597.

References

Inglut C, Sorrin A, Kuruppu T, Vig S, Cicalo J, Ahmad H . Immunological and Toxicological Considerations for the Design of Liposomes. Nanomaterials (Basel). 2020; 10(2). PMC: 7074910. DOI: 10.3390/nano10020190. View

Shimizu Y, Nakata M, Matsunuma J, Mizuochi T . Simultaneous quantification of components of neoglycolipid-coated liposomes using high-performance liquid chromatography with evaporative light scattering detection. J Chromatogr B Biomed Sci Appl. 2001; 754(1):127-33. DOI: 10.1016/s0378-4347(00)00594-6. View

Yu L . Pharmaceutical quality by design: product and process development, understanding, and control. Pharm Res. 2008; 25(4):781-91. DOI: 10.1007/s11095-007-9511-1. View

Shen J, Burgess D . Dissolution Testing Strategies for Nanoparticulate Drug Delivery Systems: Recent Developments and Challenges. Drug Deliv Transl Res. 2013; 3(5):409-415. PMC: 3779615. DOI: 10.1007/s13346-013-0129-z. View

Odeh F, Nsairat H, Alshaer W, Alsotari S, Buqaien R, Ismail S . Remote loading of curcumin-in-modified β-cyclodextrins into liposomes using a transmembrane pH gradient. RSC Adv. 2022; 9(64):37148-37161. PMC: 9075600. DOI: 10.1039/c9ra07560g. View

Amasya G, Badilli U, Aksu B, Tarimci N . Quality by design case study 1: Design of 5-fluorouracil loaded lipid nanoparticles by the W/O/W double emulsion - Solvent evaporation method. Eur J Pharm Sci. 2016; 84:92-102. DOI: 10.1016/j.ejps.2016.01.003. View

Runden E, Seglen P, Haug F, Ottersen O, Wieloch T, Shamloo M . Regional selective neuronal degeneration after protein phosphatase inhibition in hippocampal slice cultures: evidence for a MAP kinase-dependent mechanism. J Neurosci. 1998; 18(18):7296-305. PMC: 6793243. View

Johnston M, Edwards K, Karlsson G, Cullis P . Influence of drug-to-lipid ratio on drug release properties and liposome integrity in liposomal doxorubicin formulations. J Liposome Res. 2008; 18(2):145-57. DOI: 10.1080/08982100802129372. View

Filipczak N, Pan J, Yalamarty S, Torchilin V . Recent advancements in liposome technology. Adv Drug Deliv Rev. 2020; 156:4-22. DOI: 10.1016/j.addr.2020.06.022. View

10.

Ong S, Ming L, Lee K, Yuen K . Influence of the Encapsulation Efficiency and Size of Liposome on the Oral Bioavailability of Griseofulvin-Loaded Liposomes. Pharmaceutics. 2016; 8(3). PMC: 5039444. DOI: 10.3390/pharmaceutics8030025. View

11.

Rizvi S, Saleh A . Applications of nanoparticle systems in drug delivery technology. Saudi Pharm J. 2018; 26(1):64-70. PMC: 5783816. DOI: 10.1016/j.jsps.2017.10.012. View

12.

Yu M, Yuan W, Li D, Schwendeman A, Schwendeman S . Predicting drug release kinetics from nanocarriers inside dialysis bags. J Control Release. 2019; 315:23-30. DOI: 10.1016/j.jconrel.2019.09.016. View

13.

Stetefeld J, McKenna S, Patel T . Dynamic light scattering: a practical guide and applications in biomedical sciences. Biophys Rev. 2017; 8(4):409-427. PMC: 5425802. DOI: 10.1007/s12551-016-0218-6. View

14.

Santiago Franco M, Gomes E, Roque M, Oliveira M . Triggered Drug Release From Liposomes: Exploiting the Outer and Inner Tumor Environment. Front Oncol. 2021; 11:623760. PMC: 8008067. DOI: 10.3389/fonc.2021.623760. View

15.

S Fernandez M . Determination of surface potential in liposomes. Biochim Biophys Acta. 1981; 646(1):23-6. DOI: 10.1016/0005-2736(81)90266-2. View

16.

Azhar Shekoufeh Bahari L, Hamishehkar H . The Impact of Variables on Particle Size of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers; A Comparative Literature Review. Adv Pharm Bull. 2016; 6(2):143-51. PMC: 4961971. DOI: 10.15171/apb.2016.021. View

17.

Demetzos C . Differential Scanning Calorimetry (DSC): a tool to study the thermal behavior of lipid bilayers and liposomal stability. J Liposome Res. 2008; 18(3):159-73. DOI: 10.1080/08982100802310261. View

18.

Robson A, Dastoor P, Flynn J, Palmer W, Martin A, Smith D . Advantages and Limitations of Current Imaging Techniques for Characterizing Liposome Morphology. Front Pharmacol. 2018; 9:80. PMC: 5808202. DOI: 10.3389/fphar.2018.00080. View

19.

Pallagi E, Jojart-Laczkovich O, Nemeth Z, Szabo-Revesz P, Csoka I . Application of the QbD-based approach in the early development of liposomes for nasal administration. Int J Pharm. 2019; 562:11-22. DOI: 10.1016/j.ijpharm.2019.03.021. View

20.

Itoh N, Santa T, Kato M . Rapid evaluation of the quantity of drugs encapsulated within nanoparticles by high-performance liquid chromatography in a monolithic silica column. Anal Bioanal Chem. 2015; 407(21):6429-34. DOI: 10.1007/s00216-015-8805-0. View