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24 Pharmaceutical Technology ® Trends in Formulation eBook September 2024 PharmTech.com PELLETIZATION FIGURES COURTESY OF THE AUTHORS. T h e t e c h n i q u e u s e d f or p e l le t f or m a t ion i s k now n a s pe l le t i z at ion. It i nvolves t he conver- sion of ac t ive i ng red ient s i nto sm a l l, spher ica l units t y pically ranging from 0.4 to 2 millimetres in size (or larger). (Figure 1) This method confers multi-fold advantages in terms of therapeutic ef- f icac y a nd m a nu f ac t u rabi l it y. Wit h res pec t to ef f icac y, pelletization of fers advantages such as: i ncrea sed pa lat abi l it y, d i m i n i shed r i sk of dose dumping, improved dist r ibution w it h in t he gas- trointestina l (GI) tract, reduced irritation to t he GI mucosa, expedited onset of action, and modu- lated release kinetics (controlled, slow, sustained release). Whereas, and from a manufacturabilit y perspective, pelletization offers the advantages of increased f low properties, encapsulation capability, and reduceddusting. Pelletization techniques Pelletization utilizes several manufacturing tech- niques such as extrusion-spheronization, f luid bed coat i ng-powder layer i ng/solut ion layer i ng, a nd hot-melt extr usion, of fering precise control over particle size, shape, and composition. These meth- odologies are instr umental in the creation of uni- form pellets with tailored release profiles, allowing for optimized drug delivery kinetics and enhanced therapeutic outcomes. But first, it is important to understand the basics of how pellets are formed. When it comes to the primar y aspects of pellet- ization mechanisms, these include: nucleation—the initial formation of particles within a solid or liquid state; coalescence—where small nuclei collide to form larger particles; layering—where solid particles or liquid layers form over existing nuclei; abrasion— resulting in material transfer between particles and size reduction—where well-formed particles may undergo attrition-induced size reduction (Figure 2). These mechanisms involve different approaches for pellet development, including compaction and, layering. • Compaction: Compaction in pellet formation, involves the application of pressure to compress materials into denser particles. This process can be executed t h rough various t y pes of equip- ment including extruders, tablet presses, roller compactors, or pellet mills. Compaction entails subjecting a mass comprising active ingredients and excipients to mechanical force, leading to the creation of denser particles/f lakes. However, to produce spherical pellets with consistent size and shape, the widely utilized technology is the combination of an extruder and a spheronizer. This method entails extrud- ing the wet-mass or hot-melt noodles, which are then processed through the spheronizer to form spherical pellets, followed by drying. This pro- cess is crucial for achieving precise control over pellet characteristics, including size, shape, and density. By adjusting parameters such as pres- sure, dwell time, and speed of the compaction equipment, manufacturers can customize the properties of the resulting pellets to meet spe- cific and desired formulation requirements. • Layering: Layering, a fundamental technique in pellet formation, involves depositing successive layers of material onto seed particles or nuclei to construct the pellet structure. It can be executed by diverse methods, including spray coating, powder layering, or solution layering. During layering, a coating solution containing soluble active constituents or suspension (particularly for low-loading actives) is carefully applied onto FIGURE : Mechanism for pelletization. FIGURE : Curcumin of pellets.