Roorkee College of Pharmacy, Roorkee, (RCP)
Omeprazole, a widely used proton pump inhibitor, is highly effective in the treatment of acid-related gastrointestinal disorders such as gastroesophageal reflux disease (GERD), peptic ulcers, and Zollinger–Ellison syndrome. However, its acid-labile nature presents significant challenges for oral administration. Omeprazole Pellets formulated as per Indian Pharmacopoeia (IP) standards provide an effective solution through enteric coating and controlled-release strategies, ensuring drug stability and targeted intestinal delivery. This review provides a concise overview of the formulation components, manufacturing techniques (including extrusion–spheronization and fluid bed coating), and critical evaluation parameters such as particle size distribution, drug content, dissolution profile, enteric coating integrity, and stability. Additionally, it highlights the versatility of omeprazole pellets in various dosage forms—capsules, sachets, and orally disintegrating tablets—which enhance patient compliance, especially in pediatric and geriatric populations. Advances in polymer science and pelletization technology continue to improve the therapeutic performance and commercial relevance of omeprazole pellet formulations.
Omeprazole is a benzimidazole derivative that irreversibly inhibits the H+/K+ ATPase enzyme system of gastric parietal cells. Its poor stability in acidic pH necessitates the use of a multi-particulate dosage form with enteric coating. The Indian Pharmacopoeia (IP) outlines specific criteria for the quality and release of Omeprazole Pellets IP.
Omeprazole is a widely used proton pump inhibitor (PPI) that effectively suppresses gastric acid secretion by inhibiting the H?/K?-ATPase enzyme system in the parietal cells of the stomach. Since its approval in the late 1980s, omeprazole has become a cornerstone in the management of acid-related gastrointestinal disorders, including gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), and Zollinger-Ellison syndrome (Fass & Ofman, 2002).
The drug's efficacy, safety profile, and ease of administration have contributed to its widespread use in both prescription and over-the-counter forms. Omeprazole not only provides symptomatic relief but also facilitates mucosal healing, making it essential in both acute and maintenance therapy (Vakil et al., 2006). Despite its favorable safety record, concerns about long-term use—including risks of nutrient malabsorption, renal impairment, and microbiome alterations—have spurred ongoing research and debate in the clinical community (Freedberg et al., 2017).
This review aims to summarize the pharmacological properties, clinical applications, and emerging concerns associated with long-term omeprazole therapy, drawing on recent advances and evidence-based perspectives.
2. Need for Pellet Formulation [6-7]
Pelletization provides multiple advantages including improved bioavailability, site-specific drug delivery, and reduced gastric irritation. Omeprazole pellets are designed to prevent degradation in the stomach and ensure release in the upper intestine where absorption occurs.
Pellet formulations have become increasingly important in the development of oral drug delivery systems, particularly for acid-labile drugs like omeprazole. These formulations consist of small, free-flowing, spherical granules typically coated with functional polymers to achieve controlled release, taste masking, or protection from gastric acid.
One of the key reasons for using pellet technology in omeprazole formulation is to prevent its degradation in the acidic environment of the stomach. Omeprazole is highly unstable at low pH and requires enteric coating to ensure it passes through the stomach intact and releases the drug in the more alkaline environment of the intestine Pellets allow for uniform coating, which is essential for consistent drug release and bioavailability.
Moreover, multiparticulate systems like pellets offer several advantages over single-unit dosage forms, including improved patient compliance, reduced risk of dose dumping, and more predictable gastric emptying (Vervaet & Remon, 2005). They also allow flexibility in dose adjustment and combination therapy, making them suitable for pediatric and geriatric populations.
Given these benefits, pellet-based formulations have become the preferred choice for omeprazole and similar proton pump inhibitors to ensure stability, efficacy, and patient-friendly dosage forms.
3. Composition and Formulation [8, 9]
The formulation of omeprazole presents unique challenges due to its acid-labile nature and limited solubility, necessitating innovative pharmaceutical strategies to ensure stability, bioavailability, and therapeutic efficacy. The most commonly employed method is the enteric-coated pellet formulation, which allows omeprazole to bypass the acidic environment of the stomach and be released in the intestine where it remains stable and bioavailable.
1. Core Composition
The pellet core typically contains:
2. Seal-Coating Layer
A seal coat is often applied over the core to:
3. Enteric Coating
The enteric coating protects omeprazole from gastric acid and ensures release in the duodenum. Key polymers include:
4. Outer Coating (Optional)
A protective outer coating may be used for:
5. Final Dosage Form
The enteric-coated pellets are typically encapsulated in hard gelatin capsules or compressed into multi-unit tablets. These dosage forms offer the advantages of:
4. Manufacturing Techniques [10, 11]
The production of omeprazole pellets involves sophisticated pharmaceutical processes aimed at achieving high stability, controlled release, and batch-to-batch uniformity. The following are the most commonly employed manufacturing techniques in the development of omeprazole pellet formulations:
1. Extrusion–Spheronization
Extrusion–spheronization is one of the most widely used techniques for producing uniform, spherical pellets with excellent flow properties and surface smoothness. The process typically involves the following steps:
This method is especially suitable for high drug-loading formulations and allows for uniform coating in later stages.
2. Fluid Bed Coating
Fluid bed coating is the most preferred method for applying functional coats (e.g., seal coating, enteric coating) to omeprazole pellets. This technique involves suspending pellets in an upward flow of air and spraying coating solutions or dispersions onto them in a controlled environment. It offers several advantages:
Fluidized bed systems are used to apply both the acid-resistant enteric layer and protective subcoats, which are critical for protecting omeprazole from degradation.
3. Pan Coating (Less Common for Pellets)
Pan coating, though traditionally used for tablets, can also be employed for pellets in small-scale or specific cases. In this method, pellets are rotated in a coating pan while the coating solution is sprayed and dried. However, due to less control over coating uniformity and efficiency compared to fluid bed coating, it is less commonly used for multiparticulate systems like omeprazole pellets.
Summary of Techniques
|
Technique |
Key Use |
Advantages |
Disadvantages |
|
Extrusion–Spheronization |
Pellet formation |
Uniform size and shape, good flow properties |
Requires moisture-sensitive materials |
|
Fluid Bed Coating |
Enteric & seal coating |
Even coating, scalable, efficient |
High equipment cost |
|
Pan Coating |
Optional/backup coating method |
Simple setup, familiar process |
Uneven coating, less suitable for pellets |
5. Evaluation Parameters [12-14]
The quality and performance of omeprazole pellet formulations are determined by a series of evaluation parameters that ensure the final product meets pharmacopeial and regulatory standards. According to the Indian Pharmacopoeia (IP) and other global guidelines, these evaluations are crucial for confirming controlled release behavior, stability, and acid resistance, which are essential for omeprazole's therapeutic efficacy.
1. Particle Size Distribution
Uniform particle size is critical for consistent drug release, coating uniformity, and flow properties during capsule filling or compression. The distribution is typically measured using sieve analysis or laser diffraction techniques. A narrow particle size distribution ensures:
2. Drug Content and Assay
This test confirms that each batch of pellets contains the labeled amount of omeprazole. It is typically performed using High-Performance Liquid Chromatography (HPLC) as per IP or USP methods. Acceptance criteria often allow ±5% variation from the label claim. Uniform drug content ensures dose consistency and therapeutic reliability.
3. Disintegration and Dissolution Testing
Omeprazole pellets must resist disintegration in acidic pH (typically 0.1 N HCl for 2 hours) and release the drug rapidly in alkaline pH (pH 6.8 phosphate buffer). As per IP standards:
4. Enteric Coating Integrity
The integrity of the enteric coating is evaluated through acid resistance testing, scanning electron microscopy (SEM), or visual inspection of coating defects. An intact enteric coating is essential for:
5. Stability Studies [15-17]
Omeprazole is sensitive to moisture, heat, and light. Stability testing is performed under ICH guidelines to assess:
Typical conditions include:
Packaging (e.g., aluminum-aluminum blisters) plays a vital role in protecting omeprazole from environmental degradation.
According to IP standards, the pellets should release omeprazole in a controlled manner after resisting acidic conditions for a specified period.
6. Applications and Market Relevance [18-22]
Omeprazole pellets represent a highly versatile and clinically significant formulation of a proton pump inhibitor (PPI) used extensively in the management of acid-related gastrointestinal disorders. Due to the drug’s acid-labile nature, pellet-based systems offer enhanced protection, targeted release, and improved patient outcomes. Their formulation in various oral dosage forms has expanded therapeutic reach and addressed key compliance barriers in vulnerable populations.
1. Applications of Omeprazole Pellets
a. Capsule Formulations
Omeprazole pellets are most commonly filled into hard gelatin capsules, where multiple units (pellets) ensure:
b. Sachet Formulations
Pellets are also packaged in sachets for oral suspension, particularly:
c. Orally Disintegrating Tablets (ODTs)
Innovative formulations have incorporated enteric-coated omeprazole pellets into ODTs. These tablets:
Example: Zegerid® ODT, a branded formulation combining omeprazole and sodium bicarbonate, demonstrates the market demand for easy-to-administer omeprazole forms.
2. Advantages of Pellet-Based Formulations
3. Market Relevance and Demand
Omeprazole remains one of the most widely prescribed medications globally for conditions such as:
According to market data:
Generics and branded versions of omeprazole pellets are manufactured by leading pharmaceutical companies globally, including:
CONCLUSION
Omeprazole Pellets IP represent a scientifically advanced and pharmaceutically reliable delivery system specifically engineered to overcome the challenges associated with the oral administration of acid-labile drugs. Omeprazole, being highly unstable in acidic environments, requires protection until it reaches the alkaline pH of the intestine, where it exerts its proton pump inhibitory action. Pellet-based formulations provide a multi-unit particulate system (MUPS) that offers superior control over drug release, absorption, and therapeutic consistency.
REFERENCES
Amit Adhikari *, Dr. Amit Chaudhary, Anas Khan, Formulation, Evaluation, and Applications of Omeprazole Pellets IP: A Brief Review, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 5, 2503-2509. https://doi.org/10.5281/zenodo.15426341
10.5281/zenodo.15426341
