Optimization and Formulation of Emtricitabine-Loaded Liposomes Using a Box-Behnken Design
Abstract
Objective: The goal of this study was to use a Quality by Design (QbD) approach to create and improve liposomal formulations of Emtricitabine, an anti-HIV drug, to make it better at trapping other substances. Methods: A Box-Behnken Design (BBD) with three factors and three levels was used to systematically look at how the independent variables- Soy Lecithin (60–70%), Cholesterol (20–30%), and Palmitic Acid (5–10%)—affected the dependent variable, Entrapment Efficiency (EE %). We made and tested fifteen different formulas. Results: The statistical analysis of the BBD indicated that a Linear model was sufficient to describe the design space, as higher-order models were not significant. The ANOVA for the linear model yielded an F-value of 1.00 (p=0.4289), signifying that the model was not significant in relation to noise. None of the individual factors (Soy Lecithin, p=0.5831; Cholesterol, p=0.2393; Palmitic Acid, p=0.3099) demonstrated a statistically significant effect on EE within the studied ranges. However, the lack of fit was non-significant (p=0.9515), confirming the model's adequacy. A confirmation batch prepared with 70% Soy Lecithin, 20% Cholesterol, and 10% Palmitic Acid yielded an EE of 66.96%, which was within the 95% prediction interval (53.21% - 81.30%) of the predicted value (67.25%). Conclusion: Liposomal formulation of Emtricitabine was optimised and prepared with significant entrapment efficiency, which made possible to test it further through in vitro and in vivo studies.
Keywords: Emtricitabine, Liposomes, Box-Behnken Design, Entrapment Efficiency, Quality by Design, Optimization, Anti-HIV.
Keywords:
Emtricitabine, Liposomes, Box-Behnken Design, Entrapment Efficiency, Quality by Design, Optimization, Anti-HIVDOI
https://doi.org/10.22270/jddt.v16i1.7508References
1. De Clercq E. Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. International Journal of Antimicrobial Agents. 2009;33(4):307-320. https://doi.org/10.1016/j.ijantimicag.2008.10.010 PMid:19108994
2. Gray L, & Tachedjian, G. (). The discovery and development of Emtricitabine. Expert Opinion on Drug Discovery. 2017;12(6):581-588.
3. Allen T M, & Cullis PR (2013). Liposomal drug delivery systems: From concept to clinical applications. Advanced Drug Delivery Reviews, 65(1), 36-48. https://doi.org/10.1016/j.addr.2012.09.037 PMid:23036225
4. Yeagle PL. Cholesterol and the cell membrane. Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes, 1985; 822(3-4),:267-287. https://doi.org/10.1016/0304-4157(85)90011-5
5. Van Hoogevest P & Wendel A. The use of natural and synthetic phospholipids as pharmaceutical excipients. European Journal of Lipid Science and Technology. 2014;116(9): 1088-1107. https://doi.org/10.1002/ejlt.201400219 PMid:25400504 PMCid:PMC4207189
6. Huang R, Song H, Wang X, Shen H, Li S, Guan X. Fatty acid-modified liposomes for encapsulation of bioactive peptides: fabrication, characterization, storage stability and in vitro release. Food Chem. 2024;440:138139. https://doi.org/10.1016/j.foodchem.2023.138139 PMid:38134830
7. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH Q8(R2): pharmaceutical development. Geneva: ICH; 2009
8. Ferreira SLC, Bruns RE, Ferreira HS, Matos GD, David JM, Brandão GC, da Silva EGP, Portugal LA, dos Reis PS, Souza AS, dos Santos WNL. Box-Behnken design: an alternative for the optimization of analytical methods. Anal Chim Acta. 2007;597(2):179-186. https://doi.org/10.1016/j.aca.2007.07.011 PMid:17683728
9. Maheshwari S, Singh A, Khalilullah H, Verma A. Development, optimization, and characterization of emtricitabine-loaded liposomes using Box-Behnken design for enhanced drug delivery. Biomed Mater Devices. 2025. https://doi.org/10.1007/s44174-025-00466-3
10. Sharma A, Sharma US. Liposomes in drug delivery: progress and limitations. Int J Pharm. 1997;154(2):123-140. https://doi.org/10.1016/S0378-5173(97)00135-X
Published
Abstract Display: 17 
PDF Downloads: 6 PDF Downloads: 3 How to Cite
Issue
Section
Copyright (c) 2026 Ratanlal Vishwakarma , Shubhrat Maheshwari , Aditya Singh , Amita Verma
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
How to Cite
.