INTRODUCTION:

Oral drug delivery is favored for ease and compliance, but BCS Class II and IV drugs often face poor bioavailability due to low solubility or permeability. Nanotechnology improves solubility and controlled release, yet nanoparticles can degrade in gastric acid. Enteric-coated nanoparticles address this by offering pH-sensitive protection, enabling targeted intestinal release and improved absorption—especially for acid-labile drugs like omeprazole and erythromycin. Using polymers like Eudragit®, HPMCP, and PVAP, these systems enhance drug stability, site-specific delivery, and therapeutic efficacy.

This review highlights formulation strategies, characterization, and clinical relevance of enteric-coated nanoparticles for enhancing oral bioavailability.^1-5

Oral drug delivery remains popular due to its affordability, convenience, and high patient compliance. However, poorly soluble drugs, especially BCS Class II and IV medications, face formulation and bioavailability challenges.^6-8 Factors like solubility, permeability, GI tract stability, and absorption are crucial for effective oral delivery. Drugs like itraconazole and celecoxib (Class II) are solubility-limited, while paclitaxel and furosemide (Class IV) suffer from both poor solubility and permeability. Advanced formulation strategies, such as lipid-based carriers and nanotechnology, are needed to improve dissolution and absorption. Additionally, stomach degradation and first-pass metabolism further reduce bioavailability. Enteric-coated nanoparticles, lipid-based delivery, and mucoadhesive nanoparticles help protect drugs from degradation, promote intestinal absorption, and address pH-dependent solubility issues in the GI tract, offering a promising solution for enhancing oral drug delivery.^9-12

Enteric Coating: Concept and Mechanism:

Enteric coating is a pharmaceutical formulation technique designed to protect drugs from gastric degradation and ensure their release in the small intestine. It involves the application of pH-sensitive polymeric layers onto drug particles, tablets,^13-14 or nanoparticles, which prevent premature drug dissolution in the acidic environment of the stomach (pH 1.2–3.5) and allow release at intestinal pH (pH 6.0–7.5). Enteric coatings are particularly beneficial for acid-labile drugs, irritating drugs, and those requiring targeted intestinal absorption. Some common applications include protection of protein and peptide drugs (e.g., insulin),^15-17 delayed drug release for local intestinal action (e.g., mesalazine for ulcerative colitis), and enhancement of systemic bioavailability.¹⁸

Nanoparticles in Drug Delivery^19-27

Nanoparticles play a significant role in enhancing the delivery of poorly soluble drugs. Common types include:

a. Polymeric Nanoparticles: These are made from biocompatible and biodegradable polymers to improve drug stability and release control. Examples include PLGA for sustained release, chitosan for mucoadhesion, and alginate for pH-sensitive release in the intestine.

b. Lipid-Based Nanoparticles: These improve drug solubility and absorption while bypassing hepatic metabolism. Solid Lipid Nanoparticles (SLNs) provide stability and controlled release, while Nanostructured Lipid Carriers (NLCs) enhance drug loading and gastrointestinal absorption.

c. Inorganic Nanoparticles: Silica-based nanoparticles, such as mesoporous silica, are notable for their high drug-loading capacity and stability, often used for poorly soluble anticancer drugs like doxorubicin.

Enteric-Coated Nanoparticles:

Enteric-coated nanoparticles provide an advanced strategy for enhancing drug delivery by combining nanoparticle-based carriers with enteric coating technology.^28-32 This formulation approach improves the stability, solubility, and intestinal absorption of drugs, particularly those classified as BCS class II and IV drugs.³³

The need for enteric-coated nanoparticles arises from the limitations of conventional oral drug delivery, including poor solubility, enzymatic degradation, and extensive first-pass metabolism. These nanoparticles not only shield the drug from premature degradation but also enhance drug uptake by increasing the residence time in the gastrointestinal tract.³⁴ The integration of enteric coatings with nanoparticles offers significant advantages such as improved bioavailability, targeted release, and reduced gastrointestinal side effects.³⁵

Formulation Strategies:

There are several strategies for formulating enteric-coated nanoparticles, each offering distinct benefits in drug protection, stability, and controlled release. The most commonly employed approaches include direct coating of nanoparticles with enteric polymers, encapsulation of nanoparticles within enteric-coated capsules, and layer-by-layer (LbL) coating for controlled release.^36-39

Coating nanoparticles with enteric polymers:

One of the most effective methods involves directly coating nanoparticles with enteric polymers to ensure pH-dependent release. Polymers such as eudragit L100, hydroxypropyl methylcellulose phthalate (HPMC-P), and cellulose acetate phthalate (CAP) are commonly used for this purpose. The enteric polymer prevents premature drug release in the stomach and dissolves only in the intestinal environment, allowing for enhanced absorption.^40-47

Figure 1: Mechanism of enteric-coated nanoparticles in drug release

Encapsulation of nanoparticles within enteric-coated capsules:

Another effective strategy is to encapsulate nanoparticles within enteric-coated capsules. This approach is particularly useful for drugs that require delayed release or protection from gastric enzymes.⁴⁸ The nanoparticles are formulated using polymeric or lipid-based carriers and then loaded into enteric-coated gelatin or hydroxypropyl methylcellulose (HPMC) capsules.^49-53 These capsules prevent premature drug dissolution and ensure controlled release in the intestine.

Layer-by-layer (LbL) coating for controlled release:

The layer-by-layer coating technique is an innovative approach that enhances the functionality of enteric-coated nanoparticles. This method involves sequential deposition of alternating layers of oppositely charged polyelectrolytes, followed by an outer enteric coating. By modifying the number of layers and the polymer type, drug release kinetics can be precisely controlled. The key benefits of LbL coating include improved drug protection, sustained release properties, and enhanced mucoadhesion for better absorption.^54-58

Formulation Techniques and Characterization:

Techniques for Preparation:

Various techniques are used to formulate enteric-coated nanoparticles, each optimizing particle size, encapsulation efficiency, and release kinetics.⁵⁹

Solvent Evaporation:

The drug and polymer are dissolved in an organic solvent, emulsified in an aqueous phase, and nanoparticles form as the solvent evaporates. This technique is effective for encapsulating hydrophobic drugs, enhancing solubility and stability.

Ionic Gelation:

This mild method relies on ionic interactions between polymers and cross-linking agents, such as alginate and calcium ions, to form nanoparticles. It's ideal for sensitive biomolecules like proteins and peptides.⁶⁰

Nanoprecipitation:

The polymer-drug solution is added to a non-solvent, leading to nanoparticle formation due to solvent exchange and supersaturation. This method is suitable for lipophilic drugs with high drug loading efficiency.

Spray Drying:

Drug-polymer solutions are atomized into droplets and dried, forming nanoparticles. It's efficient for thermosensitive drugs and large-scale production, yielding stable, dry powder formulations.

Table 1: Comparison of Formulation Techniques

Method	Particle Size Range	Drug Loading Efficiency	Suitability
Solvent Evaporation	100–500 nm	Moderate to High	Hydrophobic drugs
Ionic Gelation	200–700 nm	Moderate	Peptides, proteins
Nanoprecipitation	50–300 nm	High	Lipophilic drugs
Spray Drying	500–2000nm	Moderate	Thermosensitive drugs

Characterization Parameters of Enteric-Coated Nanoparticles:

Characterization is crucial for ensuring the stability, efficacy, and controlled release of enteric-coated nanoparticles.⁶¹

Particle Size and Poly-dispersity Index (PDI):

Particle size significantly impacts absorption, biodistribution, and membrane interaction. For oral drug delivery, nanoparticles between 50–500nm enhance intestinal permeation while reducing rapid clearance. The polydispersity index (PDI) is a measure of particle size distribution, with values less than 0.3 indicating uniform and monodisperse nanoparticles. A lower PDI ensures consistent drug release profiles and predictable pharmacokinetics.⁶²

Dynamic Light Scattering (DLS) is the most commonly employed technique to measure particle size and PDI. This technique involves the scattering of laser light by particles suspended in a liquid medium, providing an accurate estimate of their hydrodynamic diameter.⁶³

Zeta Potential and Nanoparticle Stability:

The surface charge of nanoparticles and their colloidal stability in a solution are determined by the crucial property known as zeta potential. The likelihood of aggregation and sedimentation is decreased by electrostatic repulsion between particles, which is ensured by a greater absolute zeta potential value (> ±30 mV). Consequently, the stability and shelf-life of the nanoparticle formulation are improved.⁶⁴

Drug Loading and Encapsulation Efficiency:

Drug loading determines the drug-to-formulation ratio, while encapsulation efficiency reflects the percentage of the drug successfully trapped in nanoparticles.⁶⁵

Table 2: Comparison of Drug Loading and Encapsulation Efficiency for Different Formulation Methods

Method	Drug Loading (%)	Encapsulation Efficiency (%)	Suitable for
Solvent Evaporation	10–20	50–90	Hydrophobic drugs
Ionic Gelation	5–15	40–85	Peptides, proteins
Nanoprecipitation	15–25	70–95	Lipophilic drugs
Spray Drying	8–18	45–80	Thermosensitive drugs

In-vitro Drug Release in Simulated Gastric and Intestinal Fluids:

To evaluate the formulation's performance in physiological settings, the drug release profile of enteric-coated nanoparticles is investigated in simulated gastrointestinal settings.^66-67

Mechanisms of Improved Absorption:

Enteric-coated nanoparticles enhance drug absorption through several mechanisms. Mucoadhesion allows nanoparticles coated with bioadhesive polymers to interact with the intestinal mucosa, prolonging retention time and protecting the drug from enzymatic degradation, thereby improving bioavailability. Intestinal lymphatic transport facilitates drug movement through the lymphatic system, bypassing first-pass metabolism in the liver, which is especially beneficial for lipophilic drugs. Additionally, reduced first-pass metabolism ensures more drug reaches systemic circulation by protecting it from gastric degradation and utilizing alternative absorption pathways like the lymphatic system.⁶⁸

Figure 2: Mechanisms of Enhanced Absorption by Enteric-Coated Nanoparticles

Applications in Drug Delivery:

Enteric-coated nanoparticles have significantly improved drug delivery, especially for drugs needing protection from gastric degradation or targeted intestinal release. This approach ensures sustained, site-specific release while minimizing side effects. For gastrointestinal disorders, such as GERD and peptic ulcers, enteric coatings protect drugs like omeprazole from stomach acid, enhancing absorption in the intestine. Peptide and protein drugs, including insulin, benefit from enteric coatings that protect against enzymatic degradation and improve bioavailability. NSAIDs, like naproxen and ibuprofen, see reduced gastric irritation with controlled release in the intestine.⁶⁹

Current Trends and Future Perspectives:

Advancements in enteric-coated nanoparticles focus on novel polymers, hybrid nanocarriers, and innovative formulation technologies to enhance drug stability and bioavailability.^70-73

Table 3: Emerging Trends in Enteric-Coated Nanoparticles

Innovation	Advantages	Future Implications
Biodegradable Polymers	Controlled release, biocompatibility	Enhanced patient safety, regulatory approval
Hybrid Nanocarriers	Improved drug loading, targeted delivery	Optimized bioavailability for complex drugs
3D Printing	Precise dosage customization	Personalized medicine applications
AI-Based Formulation	Predictive modeling, faster optimization	Cost-effective drug development

CONCLUSION:

A revolutionary development in oral medication administration, enteric-coated nanoparticles solves issues with drug stability, solubility, and targeted release. Proton pump inhibitors, peptide-based medications, NSAIDs, and antibiotics are just a few of the therapeutic medicines that have benefited from their capacity to prevent gastric breakdown and promote regulated intestinal absorption. The effectiveness of drug encapsulation and site-specific delivery has been further enhanced by the combination of innovative biodegradable polymers and hybrid nanocarrier systems. Drug release profiles may now be precisely customized to meet the demands of each patient because to recent advancements like 3D printing and AI-driven formulation design, which are opening the door for personalized medicine. To allow for broad clinical acceptance and commercialization, however, regulatory obstacles and scale-up difficulties need to be resolved. Future research should focus on optimizing manufacturing processes, ensuring regulatory compliance, and enhancing formulation stability. With continued advancements, enteric-coated nanoparticles are poised to revolutionize drug delivery systems, improving therapeutic outcomes and patient adherence across various medical applications.

ACKNOWLEDGMENTS:

The authors express their gratitude to Jaipur National University, Jaipur, Rajasthan, for providing the necessary facilities to conduct this study.

CONFLICT OF INTERESTS:

The authors declare no conflict of interest.

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Received on 08.02.2025 Revised on 02.06.2025

Accepted on 06.08.2025 Published on 03.04.2026

Available online from April 06, 2026

Research J. Pharmacy and Technology. 2026;19(4):1869-1874.

DOI: 10.52711/0974-360X.2026.00269

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.