Addressing Technical Challenges for Liposomal Products in Dermatology

The consistent increase in sales of cosmeceutical products necessitates more robust and effective development of new products. Among the newly developed formulations, liposomal carriers play a vital role in topical dermatological applications. The are several highlighted specifications in this manner which could be listed as follows [1]:

• The similarity of bilayer structure which enables easier penetration into epidermal barrier.
• The possibility of both hydrophobic and hydrophilic drug encapsulation
• The potential transdermal effects of liposome itself (skin hydration through devoting lipids to the stratum corneum
• The proved applications within wide range of skin disorders
• Control and limiting side effects for irritant ingredients

Although there exists rich literature in this field, the number of commercial liposomal products are much less than expected. In this article, it is tried to highlight the major obstacles related to commercial development of these products and the decisions which have to be made for each aspect. These results have been prepared through extensive review of the literature (namely [2]) and hands-on practices within Sushiyant R&D labs.

1. Essential requirement for development of lean products
Throughout the variety of liposomal products and their applications, topical liposomal formulations are much more involved with this concept. Regardless of enhanced safety and efficacy, such products must be as affordable as possible for the customers. Generally speaking, the major attributes resulting in higher price of these products could be classified within three categories: Cost of phospholipids, process related procedures and solvents.
For each aspect, cost optimization involves trade-off decision making. For instance, less purified mixtures of phospholipids could be extracted from natural sources and they could be used in preparation of liposomes with different values of transition temperature and therefore the stability of them becomes an issue. Similarly, solvent recovery units could be constructed to restore the unused solvents while requiring extra costs related to the unit construction and validation of residual solvents. As a result, it is a specific decision of each company to select among different technical and economical trade-offs.

2. Poor stability of liposomal products
Theoretically, the effective stability and encapsulation efficiency of liposomes could be guaranteed through precise design of such products. The design principles cover several aspects which are discussed in different references, namely [3]. Briefly, proper selection of phospholipids and optimization of drug loading and cholesterol ratios could be beneficial in this way. These efforts could be implemented through gathering basic data from the material (or critical material attributes) and running experiments within the design of the experiment platform. Additionally, novel technologies such as photosensitive and radio-frequency activated compounds could be engaged in preparation of programmable liposomes regarding the economic considerations.

3. Scalability and Reproducibility of the Manufacturing Process
Fortunately, different methodologies have been presented for liposome preparation which are addressed well in different references (namely [4]). But unfortunately, each method is specified for a specific scale and has its own pros and cons. Small-scale optimization of any method must be implemented and the results must be scalable for large-scale manufacturing. As an example, ethanol injection method was a reliable and easy method for small scale which could be scaled up through specific configurations in higher scale or replaced with membrane contactor method which keeps the basic method’s principles the same. Meanwhile, elimination of batch-to-batch variability requires the reproducibility of the method. Such requirements could be applied by fixing the environmental parameters, manufacturing protocols and well-trained operators.

4. Regulatory Requirements
Due to widespread application of liposomal products for different indications, there exists some strict guidelines for injectable liposomal products. Such guidelines are much more strict than topical liposomal products and complete implementation of them may not be necessary but could be considered as the worst-case guides for topical product developments. On the other hand, the tendency and requirement of the pharma industry in implementation of Quality by Design (QbD) principles could be beneficial in this way. This strategy makes the validations much easier while forcing the manufacturer to establish the manufacturing procedure by recognition of highlighted safety and efficacy factors.
Finally, the enumerated issues are the basic and more highlighted challenges in topical liposomal products manufacturing, however; there are other issues that may be faced in special cases. To wrap up, challenges related to topical liposomal products are much less than other applications of liposomal formulations but the key to success of such products is to keep the cost low and the effectiveness as high as possible.
Experts in Sushiyant Derma Biotech labs are consistently involved with such challenges and found the best solutions to resolve them. Logically, due to numerous trade-offs in this way our products may not be the best case, but we assure you that nothing is better than it!
Your beauty matters, we save it for you…

References:
[1] de Leeuw, J., de Vijlder, H., Bjerring, P. and Neumann, H. (2009). Liposomes in Dermatology Today. Journal of the European Academy of Dermatology and Venereology, 23(5), pp.505–516. https://doi.org/10.1111/j.1468-3083.2009.03100.x.
[2] Levine, R.M., Pearce, T.R., Adil, M. and Kokkoli, E. (2013). Preparation and Characterization of Liposome-Encapsulated Plasmid DNA for Gene Delivery. Langmuir, 29(29), pp.9208–9215. https://doi.org/10.1021/la400859e.
[3] Schlich, M., Musazzi, U.M., Campani, V., Biondi, M., Franzé, S., Lai, F., De Rosa, G., Sinico, C. and Cilurzo, F. (2021). Design and Development of Topical Liposomal Formulations in a Regulatory Perspective. Drug Delivery and Translational Research, 12(8), pp.1811–1828. https://doi.org/10.1007/s13346-021-01089-z.
[4] Lombardo, D. and Kiselev, M.A. (2022). Methods of Liposomes Preparation: Formation and Control Factors of Versatile Nanocarriers for Biomedical and Nanomedicine Application. Pharmaceutics, 14(3), p.543. https://doi.org/10.3390/pharmaceutics14030543.