The Ultimate Guide to Coating Pharmaceutical Pellets

In the field of pharmaceutical research and development, multi-particulate oral drug delivery systems have been providing and expanding opportunities for pharmaceutical manufacturing. Since 1949, when research scientists SmithKline and French developed tiny drug pellets filled into capsules, this dosage form has gained significant popularity. Its advantages include enhanced drug dissolution, ease of coating, desirable release characteristics, and the ability to achieve sustained, controlled, or delayed drug release. Additionally, site-specific or pulsatile drug delivery can be achieved through different coating layers on each pellet. The spherical shape of pellets ensures better flow and even distribution in the gastrointestinal (GI) tract, leading to reduced GI irritation.

The pellet coating process is performed in fluid bed coaters and involves multiple stages, with different materials applied to inert core pellets in a stepwise manner. Each stage is designed to achieve a specific drug release profile at the desired location in the body.

Generally, inert core pellets are spherical in shape with uniform size, and these inert spheres are typically made from materials such as sucrose, tartaric acid, starch, microcrystalline cellulose, or silicon dioxide. The following are the different coatings used in pellet manufacturing:

1. Seal Coating

Seal coating is the first and most essential coating applied to core pellets. In this process, binders such as PVP K-30 and HPMC 5cps are dissolved in water to form a clear binder solution. This solution is then sprayed onto the core pellets to achieve a weight gain of 3-5% w/w.

This coating strengthens the core pellets and enhances their sphericity. Since multiple coating solutions will be sprayed onto the seal-coated pellets, and the fluidization process continues uninterrupted for several days until all coating stages are completed, seal coating plays a crucial role in ensuring the structural integrity of the core pellets.

2. Drug Loading

In this stage, the drug loading solution or dispersion is prepared using various materials along with the active pharmaceutical ingredient (API) and then sprayed onto the seal-coated pellets.

The most critical parameter at this stage is the assay evaluation of the drug-loaded pellets. This means that after the complete spraying of the drug loading solution, the pellets must undergo assay analysis to ensure that the drug content reaches 100%.  Since additional coating layers will be applied to the drug-loaded pellets in subsequent stages, achieving 100% assay at this stage is essential.

3. Sub-Coating

Sub-coating is similar to seal coating and is applied to protect the drug layer from removal due to abrasion and fluidization of pellets in the fluid bed coater. To ensure the drug content remains at 100% assay throughout the process, a binder solution is sprayed onto the drug-loaded pellets, providing an additional protective layer.

4. Polymer Loading

At this stage, two types of coating processes are involved: pH-dependent coating and pH-independent coating.

• pH-Dependent Coating
  
  This is a critical coating stage applied over the sub-coated pellets, as it controls the drug release mechanism under different pH conditions and time profiles within the body. This process, known as polymer coating, ensures that the drug is released at the desired site in the gastrointestinal tract.Enteric coating polymers such as HPMC phthalates, HPMC acetate succinates, or Eudragit coatings are used at various concentrations, depending on the required dissolution profile. Since this coating directly impacts the release behavior of the drug, it is considered a Critical Quality Attribute (CQA) in pellet dosage formulation.

• pH-Independent Coating
  
  This coating is applied after or over the pH-dependent coating. The coating solution is prepared using ethyl cellulose, which is a pH-independent polymer, meaning it prevents drug release under any pH conditions.Since most pellet formulations are designed for sustained or controlled release, drug release should occur primarily in the intestine rather than the stomach. To ensure that the polymer-coated pellets withstand the acidic environment of the stomach (pH 1-2) and do not release the drug prematurely, an ethyl cellulose coating is applied. This is crucial because the pellets may remain in the stomach for up to two hours before passing into the intestine.

5. Over-Coating

In this stage, the coating solution is prepared using the same binder as in the seal coating stage. However, if a specific color needs to be imparted to the polymer-coated pellets, a colorant is added to the binder solution. The spraying process continues until a uniform color is achieved, typically requiring a 3-5% w/w concentration.

Since different solvents are used at various stages of coating solution or dispersion preparation, the fluid bed coater parameters must be adjusted accordingly. Key parameters that vary from stage to stage include:

• Inlet temperature
• Bed temperature of pellets
• Atomization air pressure
• Wurster height adjustment
• Spray nozzle size
• Air distribution plate type
• % Inlet relative humidity (RH)

Careful monitoring and control of these process parameters is essential to ensure consistent coating quality throughout the process.

Anish Pharma, a world-class fluid bed manufacturer, provides precision-engineered solutions for superior pharmaceutical pellet coating. With cutting-edge technology, the company ensures uniform coating, controlled release, and unmatched efficiency in drug delivery.