Advantages of Pellets and Micropellets for Drug Delivery in Pharmaceuticals

The pharmaceutical industry continuously seeks innovative drug delivery systems to improve patient compliance, optimize therapeutic outcomes, and address diverse patient needs. Among these systems, pellets and micropellets stand out due to their versatility and ability to address challenges across various patient demographics, including pediatrics and geriatrics, as well as specific dosing and formulation requirements. Below, we delve into the many advantages of these systems and their potential applications.

This "The Excipients Week"′s edition features the insigths by Glatt Pharmaceutical Services - CDMO Unlimited specialized in the development and manufacturing of pellet systems for enhanced drug delivery (Glatt CDMO).

Pharmaceutical Pellets and Micropellets vs. Pellets in Other Applications

Pellets are small, solid particles used across various industries, including pharmaceuticals, agriculture, food, cosmetics, and industrial manufacturing. While the general concept of pellets applies to all these sectors, their design, composition, function, and sphericity differ significantly based on their intended application.

Pharmaceutical Pellets and Micropellets

1. Definition: Pharmaceutical Pellets: Small spherical particles, typically 500–1500 microns in size. Micropellets: Smaller than regular pellets, ranging from 100–500 microns.
2. Function: Used in oral drug delivery systems such as capsules, sachets, or as components in tablets. Enable controlled, sustained, or immediate drug release, improving therapeutic efficacy and patient compliance.
3. Composition: Made of active pharmaceutical ingredients (APIs) and excipients, often coated with functional polymers to modify release profiles (e.g., delayed or extended-release).
4. Sphericity: Importance: High sphericity (sphericity factor >0.9) is critical to ensure uniform coating, consistent drug release, and efficient manufacturing processes (e.g., capsule filling). Production: Achieved through controlled techniques like extrusion-spheronization, fluid bed granulation, or drug layering.
5. Key Characteristics: Precise particle size and distribution. Stringent quality and regulatory standards to ensure safety and efficacy.

Pellets in Other Applications

1. Agriculture (e.g., Fertilizer Pellets): Function: Deliver nutrients to soil for plant growth. Size: Larger than pharmaceutical pellets, typically 2–5 mm. Sphericity: Low to moderate, with irregular shapes acceptable for bulk distribution. Production: Focused on cost-efficiency, using bulk pressing or extrusion.
2. Food Industry (e.g., Snack or Feed Pellets): Function: Deliver specific nutritional content or texture in animal feed or processed food. Size: Varies based on application but generally larger and less uniform than pharmaceutical pellets. Sphericity: Moderate; smoother shapes aid in flowability and packaging but are less critical.
3. Industrial Manufacturing (e.g., Plastic Pellets): Function: Serve as raw material for plastic production. Size: Typically 2–5 mm. Sphericity: High to moderate, as uniform shapes ensure efficient melting and processing. Production: Extrusion methods ensure consistent geometry.
4. Cosmetic Applications (e.g., Scrub Pellets): Function: Provide exfoliation in skincare products. Size: Smaller, similar to micropellets in pharmaceuticals, often 100–500 microns Sphericity: High, to ensure smooth application and prevent skin irritation. Production: Uses specialized methods for uniformity and aesthetic appeal.

Pharmaceutical, agricultural, food, plastic, and cosmetic pellets serve diverse functions across industries.

• Pharmaceutical pellets (500–1500 microns) and micropellets (100–500 microns) are highly spherical, composed of APIs and excipients, and used for drug delivery with strict GMP compliance. Their production involves highly controlled processes to ensure precision.
• Agricultural pellets (2–5 mm) deliver nutrients to soil, using cost-focused production methods with moderate focus on sphericity and are minimally regulated.
• Food pellets, used for nutrition or texture, vary in size and are produced with minimal regulations with moderate complexity and sphericity to optimize flowability.
• Plastic pellets (2–5 mm), thermoplastic raw materials, require consistent geometry during production and must meet industrial standards.
• Cosmetic pellets (100–500 microns) ensure uniformity for user safety albeit minimalr egulations, with specialized but less complex production processes for gentle exfoliation in skincare.

Why Sphericity Differs Across Applications

• Pharmaceutical Use: High sphericity ensures coating uniformity, predictable drug release, and efficient manufacturing.
• Agriculture and Food: Cost-efficiency and scalability outweigh the need for perfect spheres.
• Industrial Manufacturing: High sphericity improves processing consistency and reduces waste.
• Cosmetic Products: High sphericity ensures gentle application and aesthetic value.

Pharmaceutical pellets and micropellets stand out due to their stringent requirements for sphericity, quality, and precision, driven by the need to meet therapeutic and regulatory standards. In contrast, pellets in other industries prioritize cost-effectiveness, bulk processing, or specific functional properties over geometric perfection.

Advantages of Pellets and Micropellets in Pharmaceutical Applications

1. Improved Patient Compliance for Pediatrics and Geriatrics

Both pediatric and geriatric populations often face difficulties swallowing conventional tablets or capsules. Pellets and micropellets offer a patient-friendly alternative as they can be formulated into dispersible forms, mixed with food or drinks, or encapsulated in easily swallowable capsules.

• Pediatrics: Pellets allow precise dosing for children, who require smaller and often variable doses. They can be flavored and coated to mask bitter tastes, improving acceptability.
• Geriatrics: For elderly patients with dysphagia, micropellets can be incorporated into semi-solid foods, making administration safer and more comfortable.

2. Flexible Dose Adjustments

Pellets and micropellets enable flexibility in dose titration, making them ideal for conditions where dosing needs vary among individuals or over time. By blending different pellet populations, precise dose customization is possible without reformulating the drug.

• Low Dose: Micropellets can accurately deliver small doses of highly potent drugs.
• High Dose: Multiple units can be encapsulated or compressed into a single dosage form to accommodate higher doses.

3. Enhanced Swallowing Experience

Swallowing difficulties, a common issue in certain patient groups, can be mitigated with pellet-based formulations. These multiparticulate systems reduce the risk of choking compared to large tablets or capsules. Additionally, the small size of pellets ensures smooth passage through the esophagus, enhancing patient safety and comfort.

4. Extended and Controlled Release

Pellets and micropellets can be coated with polymers to achieve extended or controlled drug release profiles, offering significant therapeutic advantages:

• Reduced Dosing Frequency: Extended-release formulations improve adherence by reducing the need for frequent dosing.
• Minimized Side Effects: Controlled release can prevent drug concentration spikes, reducing side effects and improving tolerability.
• Targeted Delivery: Coated pellets can enable site-specific release, such as in the colon for drugs targeting inflammatory bowel disease.

5. Combination Therapy and Drug Layering

Micropellets are ideal for combination therapies, where multiple drugs can be layered on the same pellet or blended into a single dosage form. This reduces pill burden for patients with complex therapeutic regimens, such as those managing hypertension or diabetes.

6. Uniform Distribution and Reduced Variability

The multiparticulate nature of pellets ensures uniform distribution in the gastrointestinal tract, minimizing the risk of dose dumping or variability in drug absorption. This is particularly advantageous for drugs with a narrow therapeutic index.

7. Stability and Robustness

Pellets and micropellets are less prone to segregation compared to powder blends, ensuring consistent drug content in each unit. Additionally, they offer improved stability for moisture-sensitive or heat-sensitive drugs due to their robust and protective coatings.

8. Technologies to Achieve Pellet Systems

Several advanced technologies are employed to manufacture pellet and micropellet systems, ensuring their functionality and versatility:

• Extrusion-Spheronization: A widely used process where a wet mass is extruded into strands and subsequently rounded into spherical pellets using a spheronizer.
• Rotor technologies: dry powder layering for moisture sensitive APIs and / or high drug loading in short time CPS technology: enables matrix pellets in one process steps via advanced rotor processing
• Spray granulation technologies: MicroPX and ProCell allow the formation of highly drug loaded (> 95 %) micropellets with narrow particle size distribution in a continuous process
• Hot-Melt Extrusion: Utilizes heat to mix and shape the drug and excipients into pellets, suitable for heat-stable formulations.
• Cryopelletization: A method where drug solutions or suspensions are dripped into liquid nitrogen to form frozen pellets, often used for thermolabile compounds.
• Prilling: A molten material is dripped through a nozzle and solidified into spherical pellets, often used for APIs or excipient carriers.
• Drug Layering & Coating Technologies: Functional coatings such as enteric or sustained-release polymers are applied to pellets in fluidized bed coaters or drum coaters to achieve desired release profiles. The starter cores are usually sugar (sugar and starch) or MCC (microcrystalline cellulose) pellets which are spherical particles of specific particle size ranges being drug layered and finally coated. Examples of ?Sugar Spheres: pharm-a-spheres Examples of MCC Spheres: Cellets, Celpheres The main difference between Sugar Spheres and MCC Spheres are: Solubility Sphericity Friability
• 3D Printing: An emerging technology enabling the precise layering of drugs and excipients into customizable pellet shapes and sizes.

Applications Across Formulations

Pellets and micropellets can be incorporated into a wide range of dosage forms:

• Capsules: Encapsulation of pellets enables easy administration and dose flexibility.
• MUPS tablets: A Multiple Unit Pellet System is composed of numerous small, drug-loaded pellets incorporated into a tablet.
• Orally Disintegrating Tablets (ODTs): These tablets disintegrate quickly, releasing micropellets that are easy to swallow.
• Suspensions: Pellets can be suspended in liquids, offering an alternative for patients who cannot tolerate solid dosage forms.

Conclusion

Pellets and micropellets represent a transformative approach in pharmaceutical drug delivery. Their versatility, patient-centric design, and ability to support complex dosing regimens make them an invaluable tool in addressing the needs of diverse patient populations. As advancements in coating technologies and manufacturing processes continue, the role of pellets and micropellets in delivering safe, effective, and patient-friendly therapies is set to expand further.

Interested in services and solutions for the development and manufacturing of pharmaceutical pellets? Get in touch with Glatt Pharmaceutical Services

Download the full Pellet Overview Poster to see the full content of the "teaser" below: