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26 Pharmaceutical Technology ® Trends in Formulation eBook September 2024 PharmTech.com Pelletization the surface of the seed particles, enabling the gradual build-up of material and resulting in the formation of multi-layered pellets. Powder layering involves the sequential or si- multaneous deposition of powdered materials onto the seed particles through various mecha- nisms, such as f luidized bed technology or pan coater. This is particularly recommended for ac- tives with low solubility and high loading. After this step, a polymeric solution coating can be applied to modify release characteristics. This method allows for precise control of over-active content and release kinetics, ultimately improv- ing the quality and efficacy of the final pellets. Pellet types Two t y pes of pel lets are com mon ly encountered: functional and non-functional. Functional pellets are designed to serve a specific purpose or function within a formulation, such as providing modified release properties, enhancing stability, or improving the overall performance of the product. These pellets are carefully formulated to meet certain criteria and requirements to achieve the desired effect in the final dosage form. For exam- ple—multivitamin pellets, diclofenac pellets, proton pump inhibitors(PPI) pellets, cQ10 pellets—with or without modified release. The manufacturing process for functional pellets varies depending on the formulation needs, whether high- or low-drug loading is required, accompanied with the release control. High-loading formulations often utilize the extrusion-spheronization technique. Here, the inner core matrix comprises the active in- gredient itself, followed by coating with a functional polymer to modify the release pattern. This approach allows for efficient encapsulation of a large amount of drug substance within the pellet. Alternatively low-loading doses are typically prepared by coating a solution onto non-functional pellets, which can be achieved through layering mechanisms. Non-functional pellets are necessary components in both pharmaceutical and nutraceutical formula- tions, serving as inert carriers or a core material es- sential for the manufacturing process and structural integrit y of pellet dosage forms. These non-f unc- tional pellets are also known as the base pellets or non-peril seed (NPS). They provide a starting point for pelletization, ensuring consistent pellet size, shape, and weight, which is crucial for achieving accurate dosing and content uniformity. Acting as carriers for active components, they create a stable matrix for the equal distribution of ingredients throughout the pellet. These pellets also serve as substrates for functional coatings applied to the pellet surface, en- hancing stability, modifying release profiles, or im- proving appearance and taste. This ensures uniform coverage and adhesion of the coating, which further enhances the quality of the final product. Various types of non-functional pellets are avail- able, for example, sugar spheres, starch spheres, tartaric acid spheres, mannitol spheres, and micro- crystalline cellulose (MCC) spheres. Each type offers unique properties suitable for specific formulation requirements, including f lowability, compressibility, and compatibility with active ingredients. Key consideration of pelletization Key considerations in the development of pellet for- mulations, requires the special attention to critical parameters that directly or indirectly impact formu- lation quality. These considerations include: coating uniformity, adhesion and performance of coating material, moisture content optimization, particle size of excipient used, and core material selection, etc. Some of these considerations are discussed below. Coating uniformity and integrity Uniform coating is crucial in pellet development, es- pecially for maintaining the integrity of the coating process and achieving the desired drug release pat- tern, which—in turn—guarantees pellet quality. To ensure these critical factors are met there must be consistent application of the coating material to each pellet. This includes drug coating, seal coating, func- tional coating, or color coating. Inadequate coating integrity may result in the failure to protect the sensi- tive core material, as the coating also serves as a pro- tective barrier, shielding the active ingredient from degradation. It also causes premature dose dumping; and variability in release rates, which can compro- mise therapeutic outcomes. There are numerous factors that can affect coat- ing integrit y, including solution variables, excipi- ent-coating agent used, equipment selection, process parameters, machine variables, and environmental conditions. Solution variables such as viscosity, per- cent solid content, and glass transition temperature of polymer should be considered during the formu- lation process as they play important roles in the Among multi-particulate formulations, pellets stand as the foremost dosage form in the market due to their versatility across various therapeutic ranges.