Formulation And Evaluation Of Self Emulsifying Drug Delivery System Of Lopinavir
DOI:
https://doi.org/10.69980/ajpr.v28i3.775Keywords:
..............Abstract
Lopinavir, a protease inhibitor used in combination therapy for the treatment of HIV-1 infection, suffers from poor oral bioavailability due to its low aqueous solubility and extensive first-pass metabolism. These challenges necessitate innovative formulation strategies to improve its therapeutic efficacy. Self-Emulsifying Drug Delivery Systems (SEDDS) have gained attention as a promising lipid-based approach for enhancing the solubility and absorption of hydrophobic drugs like lopinavir. SEDDS are isotropic mixtures of oils, surfactants, and co-surfactants that spontaneously form fine oil-in-water emulsions in the gastrointestinal tract, thereby improving drug dissolution and intestinal absorption.
This review provides a comprehensive overview of the formulation and evaluation strategies employed in the development of lopinavir-loaded SEDDS. It discusses the selection of excipients, phase diagram construction, emulsification behaviour, and formulation optimization techniques. Furthermore, the review highlights critical evaluation parameters such as droplet size, zeta potential, in vitro drug release, and stability studies. Recent advancements in nano-based self-emulsifying formulations, patent developments, and regulatory considerations are also examined. The findings underscore the potential of SEDDS to overcome the pharmacokinetic limitations of lopinavir and pave the way for improved oral delivery of antiretroviral drugs.
References
1. Walmsley S, Christian MD. The role of lopinavir/ritonavir (Kaletra) in the management of HIV infected adults. Expert Rev Anti Infect Ther. 2003 Oct;1(3):389-401. doi: 10.1586/14787210.1.3.389. Erratum in: Expert Rev Anti Infect Ther. 2004 Feb;2(1):164. PMID: 15482136. (https://pubmed.ncbi.nlm.nih.gov/15482136/ )
2. Fayed ND, Arafa MF, Essa EA, El Maghraby GM. Lopinavir-menthol co-crystals for enhanced dissolution rate and intestinal absorption. J Drug Deliv Sci Technol. 2022 Aug;74:103587. doi: 10.1016/j.jddst.2022.103587. Epub 2022 Jul 11. PMID: 35845293; PMCID: PMC9272570. (https://pmc.ncbi.nlm.nih.gov/articles/PMC9272570/ )
3. Salim M, Ramirez G, Clulow AJ, Hawley A, Boyd BJ. Implications of the Digestion of Milk-Based Formulations for the Solubilization of Lopinavir/Ritonavir in a Combination Therapy. Mol Pharm. 2023 Apr 3;20(4):2256-2265. doi: 10.1021/acs.molpharmaceut.3c00072. Epub 2023 Mar 14. PMID: 36919249; PMCID: PMC10074382. (https://pmc.ncbi.nlm.nih.gov/articles/PMC10074382 )
4. Zaslavsky, J., Allen, C. A dataset of formulation compositions for self-emulsifying drug delivery systems. Sci Data 10, 914 (2023). https://doi.org/10.1038/s41597-023-02812-w https://doi.org/10.1038/s41597-023-02812-w
5. Peng Zi, Cheng Zhang, Caoyun Ju, Zhigui Su, Yusheng Bao, Jie Gao, Juan Sun, Jiannan Lu, Can Zhang, Solubility and bioavailability enhancement study of lopinavir solid dispersion matrixed with a polymeric surfactant - Soluplus, European Journal of Pharmaceutical Sciences, Volume 134, 2019, Pages 233-245, ISSN 0928-0987, https://doi.org/10.1016/j.ejps.2019.04.022. (https://www.sciencedirect.com/science/article/pii/S0928098719301666 )
6. Uttreja P, Karnik I, Adel Ali Youssef A, Narala N, Elkanayati RM, Baisa S, Alshammari ND, Banda S, Vemula SK, Repka MA. Self-Emulsifying Drug Delivery Systems (SEDDS): Transition from Liquid to Solid—A Comprehensive Review of Formulation, Characterization, Applications, and Future Trends. Pharmaceutics. 2025; 17(1):63. https://doi.org/10.3390/pharmaceutics17010063
7. kanjani, Brajesh & Garg, Ashish & Garg, Sweta. (2016). A review on Self Emulsifying Drug Delivery System. Asian Journal of Biomaterial Research. 2. (https://www.researchgate.net/publication/313438437_A_review_on_Self_Emulsifying_Drug_Delivery_System )
8. Review Article www.ajphr.com 2020, Volume 8, Issue 1 ISSN: 2321–3647 (https://ajphr.com/ajphrfiles/uploaddir/AJPHR_810072.pdf )
9. J. Fac. Pharm. Ankara / Ankara Ecz. Fak. Derg., 47(2): 705-718, 2023 Doi: 10.33483/jfpau.1244378 (https://dergipark.org.tr/tr/download/article-file/2925519 )
10. A REVIEW ON SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEMS Nur alom Mondal, G. Lakshmi Devi*, Koruboyina shiva, Mangali mahender, Jvc sharma February 2021 IJSDR | Volume 6 Issue 2ISSN: 2455-2631 (https://www.ijsdr.org/papers/IJSDR2102035.pdf )
11. Cholakova, D., Vinarov, Z., Tcholakova, S., & Denkov, N. D. (2022). Self-emulsification in chemical and pharmaceutical technologies. Current Opinion in Colloid &Amp; Interface Science, 59, 101576. (https://doi.org/10.1016/j.cocis.2022.101576 )
12. Bancroft, WD (1915). "The Theory of Emulsification, VI". The Journal of Physical Chemistry. 19 (6): 275–309. doi:10.1021/j150157a002.
13. Joyce P, Dening TJ, Meola TR, Schultz HB, Holm R, Thomas N, Prestidge CA. Solidification to improve the biopharmaceutical performance of SEDDS: Opportunities and challenges. Adv Drug Deliv Rev. 2019 Mar 1;142:102-117. doi: 10.1016/j.addr.2018.11.006. Epub 2018 Dec 4. PMID: 30529138. ( https://pubmed.ncbi.nlm.nih.gov/30529138/ )
14. Salawi A. Self-emulsifying drug delivery systems: a novel approach to deliver drugs. Drug Deliv. 2022 Dec;29(1):1811-1823. doi: 10.1080/10717544.2022.2083724. PMID: 35666090; PMCID: PMC9176699. (https://pmc.ncbi.nlm.nih.gov/articles/PMC9176699 )
15. Review on Self Emulsifying Drug Delivery System: Novel Approach for Solubility Enhancement Patel Nitesh N.*1 , Rathva Sunil R1 ., Mr. Shah Viral H1 , Dr. Upadhyay Umesh M1 , Sigma institute Of Pharmacy1 , Department Of Pharmaceutics, Vadodara, Gujarat, INDIA Volume 1, issue 3 (2012), 1-12 , ISSN 2277-3657 International Journal of Pharmaceutical Research & Allied Sciences, ( https://ijpras.com/storage/models/article/GoEdKr9ExtwCDD7w0u2YgVfanWi0222oCbkq5cpoOZoPaSD3fYmYmNBtrvxd/review-on-self-emulsifying-drug-delivery-system-novel-approach-for-solubility-enhancement.pdf )
16. Raman Kallakunta V, Dudhipala N, Nyavanandi D, Sarabu S, Yadav Janga K, Ajjarapu S, Bandari S, Repka MA. Formulation and processing of solid self-emulsifying drug delivery systems (HME S-SEDDS): A single-step manufacturing process via hot-melt extrusion technology through response surface methodology. Int J Pharm. 2023 Jun 25;641:123055. doi: 10.1016/j.ijpharm.2023.123055. Epub 2023 May 18. PMID: 37207857; PMCID: PMC10429704. (https://pmc.ncbi.nlm.nih.gov/articles/PMC10429704 )
17. Park H, Ha ES, Kim MS. Current Status of Supersaturable Self-Emulsifying Drug Delivery Systems. Pharmaceutics. 2020 Apr 16;12(4):365. doi: 10.3390/pharmaceutics12040365. PMID: 32316199; PMCID: PMC7238279. (https://pmc.ncbi.nlm.nih.gov/articles/PMC7238279 )
18. Fatouros DG; Nielsen FS; Douroumis D; Hadjileontiadis LJ; Mullertz A (August 2008). "In vitro-in vivo correlations of self-emulsifying drug delivery systems combining the dynamic lipolysis model and neuro-fuzzy networks". Eur J Pharm Biopharm. 69 (3): 887–98. doi:10.1016/j.ejpb.2008.01.022. PMID 18367386. (https://www.sciencedirect.com/science/article/abs/pii/S0939641108000283?via%3Dihub )
19. Kadian R, Nanda A. A Comprehensive Insight on Self Emulsifying Drug Delivery Systems. Recent Adv Drug Deliv Formul. 2022;16(1):16-44. doi: 10.2174/2667387815666211207112803. PMID: 34875995. (https://pubmed.ncbi.nlm.nih.gov/34875995/)
20. Ravi PR, Vats R, Dalal V, Murthy AN. A hybrid design to optimize preparation of lopinavir loaded solid lipid nanoparticles and comparative pharmacokinetic evaluation with marketed lopinavir/ritonavir coformulation. J Pharm Pharmacol. 2014 Jul;66(7):912-26. doi: 10.1111/jphp.12217. Epub 2014 Feb 18. PMID: 24697749. (https://pubmed.ncbi.nlm.nih.gov/24697749/ )
21. Khan AA, Mudassir J, Akhtar S, Murugaiyah V, Darwis Y. Freeze-Dried Lopinavir-Loaded Nanostructured Lipid Carriers for Enhanced Cellular Uptake and Bioavailability: Statistical Optimization, in Vitro and in Vivo Evaluations. Pharmaceutics. 2019 Feb 25;11(2):97. doi: 10.3390/pharmaceutics11020097. PMID: 30823545; PMCID: PMC6410192. (https://pmc.ncbi.nlm.nih.gov/articles/PMC6410192/ )
22. Patel GM, Shelat PK, Lalwani AN. QbD based development of proliposome of lopinavir for improved oral bioavailability. Eur J Pharm Sci. 2017 Oct 15;108:50-61. doi: 10.1016/j.ejps.2016.08.057. Epub 2016 Aug 30. PMID: 27586019. (https://pubmed.ncbi.nlm.nih.gov/27586019/ )
23. Klein CE, Chiu YL, Awni W, Zhu T, Heuser RS, Doan T, Breitenbach J, Morris JB, Brun SC, Hanna GJ. The tablet formulation of lopinavir/ritonavir provides similar bioavailability to the soft-gelatin capsule formulation with less pharmacokinetic variability and diminished food effect. J Acquir Immune Defic Syndr. 2007 Apr 1;44(4):401-10. doi: 10.1097/QAI.0b013e31803133c5. PMID: 17224848. (https://pubmed.ncbi.nlm.nih.gov/17224848/ )
24. Khan AA, Akhtar S, Yadav Y, Atiya A, Alelwani W, Bannunah AM, Mahmood S. Lopinavir-Loaded Self-Nanoemulsifying Drug Delivery System for Enhanced Solubility: Development, Characterisation and Caco-2 Cell Uptake. Curr Drug Deliv. 2023;20(10):1474-1486. doi: 10.2174/1567201819666220817111054. PMID: 35980056. (https://pubmed.ncbi.nlm.nih.gov/35980056/)
25. Patel G, Shelat P, Lalwani A. Statistical modeling, optimization and characterization of solid self-nanoemulsifying drug delivery system of lopinavir using design of experiment. Drug Deliv. 2016 Oct;23(8):3027-3042. doi: 10.3109/10717544.2016.1141260. Epub 2016 Feb 16. PMID: 26882014. (https://pubmed.ncbi.nlm.nih.gov/26882014/ )
26. Ayed OBH, Lassoued MA, Bahloul B, Sfar S. Self-emulsifying Drug Delivery System for Improved Dissolution and Oral Absorption of Quetiapine Fumarate: Investigation of Drug Release Mechanism and In-vitro Intestinal Permeability. Iran J Pharm Res. 2021 Summer;20(3):381-398. doi: 10.22037/ijpr.2021.114785.15032. PMID: 34903996; PMCID: PMC8653647. (https://pmc.ncbi.nlm.nih.gov/articles/PMC8653647/ )
27. Tanaudommongkon I, Tanaudommongkon A, Dong X. Development of In Situ Self-Assembly Nanoparticles to Encapsulate Lopinavir and Ritonavir for Long-Acting Subcutaneous Injection. Pharmaceutics. 2021; 13(6):904. https://doi.org/10.3390/pharmaceutics13060904
28. Łyszczarz E, Sosna O, Srebro J, Rezka A, Majda D, Mendyk A. Electrospun Amorphous Solid Dispersions with Lopinavir and Ritonavir for Improved Solubility and Dissolution Rate. Nanomaterials. 2024; 14(19):1569. https://doi.org/10.3390/nano14191569
29. Anuj G. Agrawal, Ashok Kumar, Paraag S. Gide, Self emulsifying drug delivery system for enhanced solubility and dissolution of glipizide, Colloids and Surfaces B: Biointerfaces, Volume 126, 2015, Pages 553-560, ISSN 0927-7765, https://doi.org/10.1016/j.colsurfb.2014.11.022. (https://www.sciencedirect.com/science/article/pii/S0927776514006456 )
30. WIPO Publication No. 946/1E ISBN 978-92-805-2162-7 ( https://www.wipo.int/edocs/pubdocs/en/patents/946/wipo_pub_946.pdf )
31. United States Patent Application Publication Pub. No.: US 2014/0066468 A1 US 20140.066468A1 Parthasaradhi Reddy et al. Pub. Date: Mar. 6, 2014 AMORPHOUS FORM OF LOPINAVIR AND RITONAVIR, MIXTURE (https://patents.google.com/patent/US20140066468A1/en )
32. INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCТ), World Intellectual Property Organization International Bureau WIPO OMp, International Publication Date 11 October 2001 (11.10.2001) PCT International Publication Number WO 01/74787 AЗ (https://patents.google.com/patent/CA2403635A1/en )
33. IJRPC 2011, 1 Sunitha et al. ISSN: 22312781 828 INTERNATIONAL JOURNAL OF RESEARCH IN PHARMACY AND CHEMISTRY Available online at www.ijrpc.com NOVEL SELF-EMULSIFYING DRUG DELIVERY SYSTEM- AN APPROACH TO ENHANCE BIOAVAILABILITY OF POORLY WATER SOLUBLE DRUGS R. Sunitha1*, D. Satya Sireesha1 and M.V. L. Aparna (https://www.ijrpc.com/files/000012.pdf )
34. INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT), World Intellectual Property Organization International Bureau, International Publication Number, International Publication Date 27 August 2015 (27.08.2015), WO 2015/125082 Al (https://patentimages.storage.googleapis.com/92/7d/01/912c63de5397ad/WO2015125082A1.pdf )
35. Khatak, Dr & Dureja, Harish. (2015). Recent Techniques and Patents on Solid Lipid Nanoparticles as Novel Carrier for Drug Delivery. Recent Patents on Nanotechnology. 9. 150-177. 10.2174/1872210510999151126105754. (https://www.researchgate.net/publication/287108838_Recent_Techniques_and_Patents_on_Solid_Lipid_Nanoparticles_as_Novel_Carrier_for_Drug_Delivery )
36. Yedi Herdiana, Nasrul Wathoni, Shaharum Shamsuddin, Muchtaridi Muchtaridi, Scale-up polymeric-based nanoparticles drug delivery systems: Development and challenges, OpenNano, Volume 7, 2022, 100048, ISSN 2352-9520, https://doi.org/10.1016/j.onano.2022.100048. (https://www.sciencedirect.com/science/article/pii/S2352952022000111 )
37. Alhumaid S, Al Mutair A, Al Alawi Z, Alhmeed N, Zaidi ARZ, Tobaiqy M. Efficacy and Safety of Lopinavir/Ritonavir for Treatment of COVID-19: A Systematic Review and Meta-Analysis. Tropical Medicine and Infectious Disease. 2020; 5(4):180. https://doi.org/10.3390/tropicalmed5040180 (https://www.mdpi.com/2414-6366/5/4/180 )
38. Maharana, Rajib & Swain, Surya Kanta & Mahapatra, Santosh & Jena, Bikash Ranjan. (2024). Self-Emulsifying Drug Delivery Systems: Concept to Applications, Regulatory Issues, Recent Patents, Current Challenges and Future Directions. Current pharmaceutical biotechnology. 25. 10.2174/0113892010296223240612050639. (https://www.researchgate.net/publication/381660705_Self-Emulsifying_Drug_Delivery_Systems_Concept_to_Applications_Regulatory_Issues_Recent_Patents_Current_Challenges_and_Future_Directions)
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