Potential Of Self Microemulsifying Drug Delivery System: An Overview

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Technical Review Article | Open Access | Published 26th March 2026

Potential Of Self Microemulsifying Drug Delivery System: An Overview

Patidar Yogita, Gupta Ashish*, Sharma Ravi, Darwhekar Gajanan | EJPPS | 311 (2026) https://doi.org/10.37521/ejpps31109

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Abstract

Self-microemulsifying drug delivery systems (SMEDDS) are a promising method for improving the bioavailability of water-soluble drugs. These systems form fine oil-in-water micro emulsions in the gastrointestinal tract, eliminating high-energy input and ensuring uniform formulations. However, they face challenges such as component selection and potential side effects. SMEDDS are used in the pharmaceutical industry for class II and IV drugs and are advancing with emerging technologies and multidisciplinary collaborations.

Keywords: Self-Microemulsifying Drug Delivery Systems (SMEDDS), Poorly Water-Soluble Drugs, Oral Drug Delivery, Oil-in-Water Microemulsions, Surfactants and Co-surfactants.

Introduction

The oral route of administration is the preferred choice for ongoing drug therapy, but researchers have struggled to increase the bioavailability of medications that are not very soluble in water. Lipophilic medicines are among the medications that suffer from low oral bioavailability and researchers are exploring various methods to improve their solubility. Microemulsions are being explored as a potential new colloidal delivery system for lipophilic medications, offering advantages such as superior drug solubilization ability, thermodynamic stability, increased oral bioavailability, and safety. However, their high fat content and water content make them unsuitable for anhydrous self-emulsifying drug delivery systems. The ‘Self-Micro Emulsifying Drug Delivery System’ device (SMEDDS) is a lipid-based device that has been shown to improve the oral bioavailability of lipophilic medications. The SMEDDS approach forms oil-in-water micro emulsions, enhancing the solubility of water-insoluble medications. However, improving pharmacodynamic effects and oral bioavailability is crucial. Researchers are focusing on creating effective tablet dosage forms by combining the advantages of liquid SMEDDS with solid formulations in a solid dosage form. (Tamboli et al, 2024).

SMEDDS: Self-emulsifying drug delivery systems (SMEDDS) are isotropic blends of surfactants, oils, or hydrophilic solvents that create fine oil-in-water microemulsions when agitated and diluted in aqueous media. SMEDDS distribute easily throughout the gastrointestinal tract, and their physical stability allows for improved absorption rates and repeatable blood-time profiles for lipophilic medicinal molecules. The first step is finding an appropriate oil surfactant mixture, which can be packed in gelatin capsules. Co-surfactants and co-solvents are often added to enhance their properties. (Reddy and Gubbiyappa, 2021)

Fig 1: Emulsification and Drug Solubilization

Use of SMEDDS belonging to multitudinous BCS class drugs:

BCS Classification	Aqueous solubility	Membrane permeability	Hurdles overcome by SMEDDS
I	High	High	Enzymatic declination, Gut wall efflux
II	Low	High	Solubilization, Bioavailability
III	High	Low	Enzymatic declination Gut wall efflux, Bioavailability
IV	Low	Low	Solubilization, Enzymatic declination, Gut wall efflux, Bioavailability

Lipid formulation classification system: This classification helps to better understand the fate of various lipid formulation in vivo. It also helps to use a systematic and rational formulation approach to avoid trial and error. This system was established by Pouton in 2000 and recently updated. Based on the type of components divided into 4 types, this shows the possible effects of dilution and digestion on their ability to prevent drug precipitation (Tran and Park, 2021)

Type I: This lipid simple formulation consists of highly lipophilic compounds in which oil is present without surfactant, such as glycerides which are non-dispersing requiring digestion. This is generally safe, but the formulation has poor solvent capacity (Radha et al, 2019) (Jadhav et al, 2024).

Type II: This lipid formulation consists of SEDDs, oils and water with insoluble surfactant dispersion, allowing drug absorption without digestion, and classified into type IIA and type IIB. (Radha et al, 2019) (Jadhav et al, 2024).

Type III: Lipid-based formulations commonly used for SMEDDS, consisting of oil, surfactant/cosurfactant which are water soluble with clear or almost clear hydrophilicity. Type IIIB formulation has greater dispersion when compared with Type IIIA (Radha et al, 2019) (Jadhav et al, 2024).

Type IV: This is a formulation containing predominantly hydrophilic surfactant and cosurfactant which does not contain any natural lipid. Formulation dispersion typically forms micellar solutions having good solvent capacity for many drugs (Radha et al, 2019) (Jadhav et al, 2024).

The History of Microemulsions In 1943 Hoar and Shulman, chemistry professors at Cambridge University, coined the word "microemulsion"(Anand et al, 2016).

Mechanism of self-emulsification: Self-emulsification occurs when the energy needed to expand a dispersion's surface area is less than the entropy change favouring dispersion. The free energy of the typical emulsion is determined by the formula ∆G=∑Niπri2S. Emulsification stabilizes the emulsion by separating the two phases over time, decreasing the interfacial area. Pouton suggests a connection between phase inversion behaviour and surfactant emulsification characteristics. When non-ionic surfactants stabilize the oil-in-water system, phase inversion occurs, reducing the o/w interfacial energy and reducing emulsification energy. (Maurya et al, 2017) (Mohanty et al, 2022).

Advantages of SMEDDS: -

Enhanced oral bioavailability: The bioavailability of weakly water-soluble substances is limited by dissolution rate-dependent absorption. SMEDDS improves bioavailability by delivering the medication in a solubilized, microemulsified form, increasing specific surface area for effective drug transport through the intestinal aqueous boundary layer. (Kyatanwar et al, 2010).
Manufacturing simplicity and scalability: SMEDDS stands out due to its ease of manufacturing and scaling up, requiring basic and affordable facilities such as a mixer and agitator, making it a popular choice in the industry. (Kyatanwar et al, 2010) (Vaghela et al, 2021).
Decrease in dietary effects and intra- and inter-subject variability: SMEDDS significantly improves medication absorption and performance, despite food impact, by providing reproducible plasma profiles and performance independent of meals in numerous research studies. (Vaghela et al 2021)
Capacity to transport peptides that are susceptible to GIT enzymatic hydrolysis: SMEDDS are unique drug delivery systems that can carry macromolecules such as peptides, hormones, enzyme substrates, and inhibitors, and protect against enzymatic hydrolysis, making them ideal for thermolabile medications without energy or heating. (Kalamkar et al, 2016).
No impact on the process of lipid digestion: SMEDDS, unlike other lipid-based drug delivery systems, does not undergo lipolysis, allowing the drug to be absorbed through its micro emulsified form. (Prasad et al, 2023).
Enhanced ability to load drugs: In addition, SMEDDS offer the benefit of greater drug loading capacity in contrast with traditional lipid solutions because the solubility of weakly water-soluble medications with an intermediate partition coefficient (24) is generally higher in amphiphilic surfactants, co-surfactants, and co-solvents and lower in natural lipids (Parmar et al, 2012).

Disadvantages of SMEDDS

No reliable predictive in vitro models exist for evaluating the formulations.
In vitro models require more refinement and verification.
Since future research will rely on correlations between in vitro and in vivo models, various prototype lipid-based formulations must be created and evaluated in vivo using an appropriate animal model.
Moreover, volatile co-solvents in the traditional self-microemulsifying formulations are known to migrate into the shells of soft or hard gelatin capsules, causing the precipitation of the lipophilic drugs.
Chemical instabilities of drugs and high surfactant concentrations in formulations (roughly 30–60%) that irritate the GIT are other factors to be considered.

The hydrophilic solvent's dilution impact may increase the drug's precipitation tendency upon dilution (Anand et al, 2016) (Dokania and Joshi, 2015).

Formulation components of SMEDDS

Active pharmaceutical ingredient
Oil
Surfactant
Co-surfactant
Co-solvents

Active pharmaceutical ingredient: The drug's solubility in the oil phase affects SMEDDS's capacity to preserve the API in its solubilized state. Lipophilic medications, such as cinnarizine are an excellent fit for SMEDDS if their log p is greater than 5 (Parmar et al, 2012).
Oil: Since it solubilizes the lipophilic medication in the necessary proportion, oil is the most crucial excipient in the formulation of SMEDDS. The drug's great solubility in the oil is the primary requirement for choosing it. This will reduce the formulation's volume and ensure an effective dosage is delivered (Mohanty et al, 2022).
Surfactant:

o Anionic surfactants, in which a negative charge is carried by the hydrophilic group. Examples include sodium lauryl sulphate and potassium laurate.

o Cationic surfactants, which have a positive charge on the hydrophilic group. Quaternary ammonium halide is one example.

o Ampholytic surfactants, also known as Zwitterionic surfactants, have a positive and a negative charge. sulfobetaines, for instance.

o Nonionic surfactants, in which the highly polar groups give the hydrophilic group its water solubility despite the hydrophilic group having no charge. Examples include polysorbates (Tweens) and sorbitan esters (Spans) (Uttreja et al, 2025).

Co-surfactant: To produce an ideal SMEDDS, a high concentration of surfactant is needed to adequately lower interfacial tension, which can be hazardous. Co-surfactants are employed to lower the surfactant concentration. Co-surfactants with an HLB value of 10–14, such as ethanol, propylene glycol, and polyethylene glycol, are typically utilized (Akula et al, 2014).
Co-solvents: Organic solvents enable the dissolution of large quantities of either the hydrophilic surfactant or the drug in oil phase. Examples include ethanol, butanol, propylene glycol, etc., esters such as ethyl propionate, tributyl citrate and amides such as 2-pyrolidine, caprolactam, and polyvinyl pyrrolidine (Reddy et al, 2011) .
Other components: Other components include pH adjusters, flavours, and antioxidants, consistency builders, enzyme inhibiters, polymers, etc (Akula et al, 2014)

Formulation design of SMEDDS: a formulation study example

Oil Screening: The study examined the solubility of API in various oils using the shake flask method. The mixture was vortexed, centrifuged, and diluted with mobile phase. The drug content was measured using HPLC technology after 72 hours of equilibrium and a 0.45 μm membrane filter. (Narkhede et al, 2023).
Screening of Surfactant: The study examined the emulsifying ability of surfactants with screened oil to identify the best surfactant. An isotropic mixture was created by weighing surfactant and oil phase, vortexed, warmed, and diluted with double-distilled water. Transmittance was measured at 638 nm, and the surfactant with higher transmittance was chosen. (Mohanty et al, 2022).
Co-surfactant screening: The study examined the emulsifying potential of co-surfactants with screened oil after oil screening. An isotropic mixture was created, diluted with double-distilled water, and observed for clear emulsions. Transmittance was measured at 638 nm after two hours. The co-surfactant with a higher transmittance and fewer inversions was chosen. (Bashir et al, 2023).

Phase diagram construction

Phase diagrams were created using oil, surfactant/co-surfactant, and water to determine the percentage of components that can produce the largest microemulsion existence area. Solutions with varying weight ratios were vortexed and heated to 50°C. Weight ratios of oil and Smix were created, and mixtures were left at room temperature for a day. Water was added at intervals, and the mixtures were examined for appearance. A ternary phase diagram was created using the chosen percentages (Buya et al, 2020) (Reddy et al, 2011).

Preparation of SMEDDS: The surfactant to co-surfactant diagram ratio was optimized, and different formulations were created by adjusting the oil to Smix ratio. The surfactant and co-surfactant were weighed, vortexed, and baked at 50°C. An isotropic mixture was created, and the drug was introduced into the mixture. (Narkhedemet al, 2023).

Evaluation of SMEDDS

Determination of droplet size/distribution and zeta-potential: Photon correlation spectroscopy uses a zetasizer to detect droplet size in the 10-5000 nm range. This method, only suitable for low dilutions, can be used to assess oil droplet charge, like cationic SMEDDS, which has a positive n-potential value between 35 and 45 mV after medicinal molecules are incorporated. (Patel et al, 2013).
Rheological determination: A rotational viscometer and Brookfield viscometer Rheomat 108 can be used to assess the microemulsion's rheological characteristics. This study verifies if the system is w/o or o/w. It should be carried out three times (Rai and Rashir, 2012)
Polarity: The polarity of an oil droplet is influenced by HLB, chain length, fatty acid unsaturation, hydrophilic region molecular weight, and emulsifier concentration, affecting drug affinity and release. (Patel et al, 2013).
Dispersibility test: The USP XXII dissolution apparatus 2 is used to assess the effectiveness of oral nano- or microemulsion self-emulsification, using a grading scheme for visual evaluation.

• Grade A: A transparent or bluish looking nanoemulsion that forms quickly (within a minute).

• Grade B: A bluish-white, rapidly developing emulsion that is a little less transparent.

• Grade C: A fine, milky emulsion that develops in two minutes.

• Grade D: A dull, grayish-white emulsion that takes longer than two minutes to emulsify and has a slightly greasy appearance.

• Grade E: Emulsification, with large oil globules visible on the surface and either poor or little emulsification.

When distributed in GIT, Grade A and Grade B formulations will continue to be nanoemulsions. However, Grade C formulations might be suggested for SEDDS formulations (Rai and Rashir, 2012).

Turbidimetric evaluation: Nepheloturbidimetric evaluation tracks emulsion growth by measuring turbidity increase in a self-emulsifying system on a magnetic plate. However, the rate of emulsification cannot be monitored due to short emulsification time. (Patel et al, 2013).
Refractive index and transmittance percentage: A formulation's transparency is determined by measuring its refractive index and transmittance percentage. A transparent formulation has a refractive index comparable to water (1.333) and a transmittance percentage greater than 99%. (Anand et al, 2016).
Electro conductivity test: The purpose of this test is to measure the system's electroconductive character. An electro-conductometer is used to test the electroconductivity of the resulting system. Because free fatty acids are present in typical SMEDDSs, an oil droplet has a negative charge (Cai et al, 2014).
Drug content: The drug is extracted from pre-weighed SMEDDS by dissolving it in an appropriate solvent. Using an appropriate analytical technique, the drug content in the solvent extract is compared to the drug's standard solvent solution (Sha et al, 2012).
In vitro dissolution testing: The US Pharmacopoeia XXIV dissolution apparatus 2 is used for quantitative in vitro drug release tests. The device revolves at 100 rpm and uses 900 ml of pH-specific buffer. SMEDDS formulations are placed in gelatin capsules, and HPLC analysis is performed using a 5 ml sample. (Cai et al, 2014).

Applications

Improvement in solubility and bioavailability
Super saturable SMEDDS
Protection against biodegradation

Conclusion

SMEDDS are lipid-based drug delivery systems that enhance the bioavailability of poorly soluble medications. Factors such as increased bile secretion, easier drug partitioning, and increased intestinal permeability contribute to their effectiveness. Designing successful formulations requires understanding the roles of individual lipids, surfactants, and co-surfactants, as well as the dispersion process and drug solubilization. This review focuses on physic-chemical and biopharmaceutical elements.

References

1. Akula, S., Gurram, A. K., & Devireddy, S. R. (2014). Self-Microemulsifying Drug Delivery Systems: An Attractive Strategy for Enhanced Therapeutic Profile. International scholarly research notices, 2014(1), 964051.

2. Anand, S., Gupta, R., & Prajapati, S. K. (2016). Self-micro emulsifying drug delivery system. Asian J Pharm Clin Res, 9(2), 33-38.

3. Bashir, M. A., Khan, A., Shah, S. I., Ullah, M., Khuda, F., Abbas, M., ... & Ming, L. C. (2023). Development and evaluation of self-emulsifying drug-delivery system–based tablets for simvastatin, a BCS Class II Drug. Drug Design, Development and Therapy, 261-272.

4. Benival, D. M., & Devarajan, P. V. (2015). In situ lipidization as a new approach for the design of a self microemulsifying drug delivery system (SMEDDS) of doxorubicin hydrochloride for oral administration. Journal of Biomedical Nanotechnology, 11(5), 913-922.

5. Betageri, G. V. (2019). Self-emulsifying drug delivery systems and their marketed products: a review. Asian Journal of Pharmaceutics (AJP), 13(02).

6. Buya, A. B., Beloqui, A., Memvanga, P. B., &Préat, V. (2020). Self-nano-emulsifying drug-delivery systems: From the development to the current applications and challenges in oral drug delivery. Pharmaceutics, 12(12), 1194.

7. Cai, S., Shi, C. H., Zhang, X., Tang, X., Suo, H., Yang, L., & Zhao, Y. (2014). Self-microemulsifying drug-delivery system for improved oral bioavailability of 20 (S)-25-methoxyl-dammarane-3β, 12β, 20-triol: preparation and evaluation. International Journal of Nanomedicine, 913-920.

8. Chou, Y. C., Li, S., Ho, C. T., & Pan, M. H. (2020). Preparation and evaluation of self-microemulsifying delivery system containing 5-demethyltangeretin on inhibiting xenograft tumor growth in mice. International Journal of Pharmaceutics, 579, 119134.

9. Dokania, S., & Joshi, A. K. (2015). Self-microemulsifying drug delivery system (SMEDDS)–challenges and road ahead. Drug delivery, 22(6), 675-690.

10. Friedl, J. D., Jörgensen, A. M., Le‐Vinh, B., Braun, D. E., Tribus, M., &Bernkop-Schnürch, A. (2021). Solidification of self-emulsifying drug delivery systems (SEDDS): Impact on storage stability of a therapeutic protein. Journal of Colloid and Interface Science, 584, 684-697.