Self-Nanoemulsifying Drug Delivery Systems in Soft Gelatin Capsules: Formulation Advances, Manufacturing Challenges, and Future Perspectives
Abstract
Poor aqueous solubility remains a major barrier to the successful oral delivery of a large proportion of newly discovered drug candidates, often resulting in low and variable bioavailability. Self-nanoemulsifying drug delivery systems (SNEDDS) have emerged as a robust formulation strategy to address these limitations by forming fine oil-in-water nanoemulsions upon mild agitation in gastrointestinal fluids. When incorporated into soft gelatin capsules, SNEDDS offer additional advantages, including accurate dose delivery, improved patient compliance, and enhanced protection of labile drug substances. This review provides a comprehensive overview of self-nanoemulsifying formulations specifically designed for soft gelatin capsule filling, with emphasis on formulation principles, excipient selection, and critical quality attributes governing performance. Key aspects of SNEDDS characterization, encompassing physicochemical, in vitro, and in vivo evaluation techniques, are discussed in relation to capsule compatibility, stability, and biopharmaceutical behavior. Furthermore, industrial manufacturing considerations, scale-up challenges, and regulatory expectations relevant to SNEDDS-filled soft gelatin capsules are critically examined. Current limitations, such as capsule shell interactions, precipitation risks, and long-term stability concerns, are highlighted alongside emerging technological advances, including supersaturable systems, lipid-based excipient innovations, and predictive in vitro-in vivo correlation approaches. Overall, this review underscores the evolving role of SNEDDS in soft gelatin capsule dosage forms and outlines future prospects for their expanded application in improving the oral delivery of poorly soluble drugs.
Keywords: Self-nanoemulsifying drug delivery; Soft gelatin capsules; Nano emulsions; Stability and Regulatory considerations
Keywords:
Self-nanoemulsifying drug delivery, Soft gelatin capsules, Nano emulsions, Stability and Regulatory considerationsDOI
https://doi.org/10.22270/jddt.v16i2.7546References
1. Palem CR, Rendla R, Nagamalli NK, Lekkala VK, Gumudevelli S, A Comprehensive Review of Current Trends and Regulatory Frameworks in Generic Drug Development, J. Pharm. Sci 2025;1(10):16-27. https://doi.org/10.5281/zenodo.17297703
2. Palem CR, Lekkala VK, Nagamalli NK, Balguri PR, Gumudevelli S. Next-Generation Dry Powder Inhalers: Advances in Characterization and Evolving Regulatory Frameworks, J. Pharm. Sci 2025;1(9):160-177. https://doi.org/10.5281/zenodo.17168847.
3. Date AA, Desai N, Dixit R, Nagarsenker M. Self-nanoemulsifying drug delivery systems: formulation insights, applications and advances. Nanomedicine (Lond) 2010;5(10):1595-616. https://doi.org/10.2217/nnm.10.126
4. Palem CR, Gumudevelli S, Rendla R, Srinija G, Gumudevell S. Comprehensive review on the role of Dietary Acid Load in health and its effect on different types of Diabetes. International Journal of Diabetes Research 2025; 7(1): 45-53. https://www.doi.org/10.33545/26648822.2025.v7.i1a.26
5. Palem CR, Lekkala VK, Nishanth Kumar N, Venkata Santhosh P, Gumudevelli S.Scale-Up Factors in the Development and Commercial Execution of Oral Solid Dosage Forms: A Current Industry Perspective. J Pharmacol Pharm Res Volume 2024;7(1):1-14.
6. Palem CR, Chopparapu KS, Subrahmanyam PVRS, Yamsani, MR. Cyclodextrins and their Derivatives in Drug Delivery: A Review. Current Trends in Biotechnology and Pharmacy 2012; 6(3): 255-279.
7. Thatipamula RP, Palem CR, Gannu R, Mudragada S,Yamsani MR. Formulation and in vitro characterization of Domperidone loaded solid lipid nano particles and nano structured lipid carriers 2011;19(1): 23-32.
8. Holm R, Kuentz M, Alexandra-Roxana Ilie-Spiridon, Griffin BT. Lipid based formulations as supersaturating oral delivery systems: From current to future industrial applications. European Journal of Pharmaceutical Sciences 2023;189:106556. https://doi.org/10.1016/j.ejps.2023.106556
9. Parigela V,Vijayalakshmi A. Self-Nano-Emulsifying Drug-Delivery Systems: A Limelight on the Development, Advancements and Opportunities in Improving Oral Absorption. Scope 2024;14(1):1740-1755.
10. Buya AB, Beloqui A, Memvanga PB, Préat V. Self-Nano-Emulsifying Drug-Delivery Systems: From the Development to the Current Applications and Challenges in Oral Drug Delivery. Pharmaceutics 2020;12(12) :1194. https://doi.org/10.3390/pharmaceutics12121194
11. Uttreja P, Youssef AAY, Karnik I, Sanil K, Narala N, Wang H, Elkanayati RM, Vemula SK, Repka MA. Formulation Development of Solid Self-Nanoemulsifying Drug Delivery Systems of Quetiapine Fumarate via Hot-Melt Extrusion Technology: Optimization Using Central Composite Design. Pharmaceutics 2024;16(3): 324. https://doi.org/10.3390/pharmaceutics16030324 .
12. Patel UKD, Kempwade AKA, Patil VS, Hiremath RD. Formulation and Evaluation of Self-Nanoemulsifying Drug Delivery System of Clofazimine RJPS 2022;12(1):38-46. https://doi.org/10.26463/rjps.12_3_6.
13. Pouton CW. Formulation of self-emulsifying drug delivery systems. Advanced Drug Delivery Reviews, 1997;25(1),47-58. https://doi.org/10.1016/S0169-409X(96)00490-5 .
14. Gullapalli RP. Soft gelatin capsules (softgels). Journal of Pharmaceutical Sciences, 2010; 99(10):4107–4148. https://doi.org/10.1002/jps.22151.
15. Tanga S, Ramburrun P, Aucamp ME.From liquid SNEDDS to solid SNEDDS: A comprehensive review of their development and pharmaceutical applications. The AAPS Journal 2025; 28(1):10. https://doi.org/10.1208/s12248-025-01167-x
16. Feeney OM, Crum MF, McEvoy CL, Trevaskis NL, Williams HD, Pouton CW, Charman WN, Bergström CAS, Porter CJH. 50 years of oral lipid-based formulations: Provenance, progress and future perspectives. Advanced Drug Delivery Reviews 2016; 101:167–194. https://doi.org/10.1016/j.addr.2016.04.007.
17. Pouton CW, Porter CJH. Formulation of lipid-based delivery systems for oral administration: Materials, methods and strategies. Advanced Drug Delivery Reviews 2008; 60(6):625–637. https://doi.org/10.1016/j.addr.2007.10.010.
18. Singh B, Bandopadhyay S, Kapil R, Singh R, Katare O. Self-emulsifying drug delivery systems (SEDDS): formulation development, characterization, and applications. Crit Rev Ther Drug Carrier Syst. 2009;26(5):427-521. https://doi.org/10.1615/critrevtherdrugcarriersyst.v26.i5.10
19. Williams HD, Trevaskis NL, Charman SA, Shanker RM, Charman WN, Pouton CW, Porter CJH. Strategies to address low drug solubility in discovery and development. Pharmacological Reviews 2013; 65(1): 315–499.
https://doi.org/10.1124/pr.112.005660
20. Wu F, Ma Q, Tian G, Chen K, Yang R, Shen J. Formulation and Evaluation of Solid Self-Nanoemulsifying Drug Delivery System of Cannabidiol for Enhanced Solubility and Bioavailability. Pharmaceutics. 2025; 17(3):340. https://doi.org/10.3390/pharmaceutics17030340
21. Dressman JB, Reppas. In vitro–in vivo correlations for lipophilic, poorly water-soluble drugs. European Journal of Pharmaceutical Sciences, 2000;2:S73-80. https://doi.org/10.1016/s0928-0987(00)00181-0
22. Karimi M, Mirshekari H, Moosavi Basri SM, Bahrami S, Moghoofei M, Hamblin MR. Bacteriophages and phage-inspired nanocarriers for targeted delivery of therapeutic cargos. Adv Drug Deliv Rev. 2016;106(A):45-62. https://doi.org/10.1016/j.addr.2016.03.003
23. Porter CJH, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: Optimizing the oral delivery of lipophilic drugs. Nature Reviews Drug Discovery 2007; 6(3):231–248. https://doi.org/10.1038/nrd2197.
24. Palem CR, Dudhipala NR, Battu SK, Repka MA, Yamsani MR. Development, optimization and in vivo characterization of domperidone-controlled release hot-melt-extruded films for buccal delivery. 2016, Drug Development and Industrial Pharmacy 2015;42(3):473-484. https://doi.org/10.3109/03639045.2015.1104346.
25. Rahman J, Quodbach J. Versatility on demand - The case for semi-solid micro-extrusion in pharmaceutics. Advanced Drug Delivery Reviews 2021;172:104-126. https://doi.org/10.1016/j.addr.2021.02.013
26. Palem CR, Battu SK, Maddineni S, Gannu R, Repka MA, Yamsani MR. Oral transmucosal delivery of domperidone from immediate release films produced via hot-melt extrusion technology. Pharmaceutical Development and Technology 2013:18(1):186-195. https://doi.org/10.3109/10837450.2012.693505.
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