Formulation of enteric-coated Pellets
Pellets are spheres of varying diameter depending on application and client need. Applications are found not only in the pharmaceutical industry but also in the agribusiness (e.g., fertilizer, fish food) and in the polymer industry.
In the pharmaceutical industry, Pellets can be defined as small, free-flowing, spherical particulates manufactured by the agglomeration of fine powders or granules of drug substances and excipients using appropriate processing equipment. The term also has been used to describe small rods with aspect ratios of close to unity.
Traditionally, a variety of pellets have been systematically produced as geometrically defined agglomerates obtained from diverse starting materials utilizing different processing conditions. Pellets for pharmaceutical purposes are usually produced in the size range of 0.5 to 1.5 mm. The final oral multiple-unit dosage form can be either a hard gelatin capsule filled with pellets or a tablet composed of carefully compressed pellets. Pellets are prepared using different technologies such as layering of the drug solution, suspension or powder on the inactive cores, extrusion/spheronization, and agglomeration in rotogranulators or rotoprocessors, compression, spray drying, or spray congealing.
Advantages and Applications
* Flexibility in dosage form design and development
* Combination of different release rates of the same drug in a single dosage form
* Controlled release technology
* Free dispersion in the GI & invariably maximize drug absorption
* Reduction of peak plasma fluctuation
* Minimization of potential side effects without lowering bioavailability
* Avoidance of high local concentration
* Less susceptibility to dose dumping
* Reduction of gastric emptying rates to minimize inter and intra subject variability of plasma profile
* Low surface area to volume ratio and provision of ideal shapes for the application of film coatings
* Reproducible fill weights in capsules
* Flexibility to mix incompatible drugs
Pellet Formation and Kinetics
Fine powders can readily be formed into agglomerates by the introduction of a liquid phase followed by suitable agitation or tumbling. The liquid and solid phases are brought into close contact; this allows binding forces to develop and bring about agglomeration. Growth of the particles occurs either by collisions and
successful adherence of primary feed particles onto which particles collide and attachés themselves. This result in pellet growth formation.
Pelletization and Techniques
Pelletization is an agglomeration process that converts fine powders or granules of bulk drugs and excipients into small, free-flowing, spherical or semi-spherical units, generally of size range 0.5-1.5 mm.
Powder layering involves the deposition of successive layers of dry powder of drug or excipients or both on preformed nuclei or cores with the help of a binding liquid.
Solution/ Suspension Layering
During processing, the formulation components are dissolved or suspended in an application medium and sprayed onto a product bed to impinge on the starter seeds. A drying phase renders dissolved materials to precipitate and form solid bridges, which continues until the desired pellet target potency is achieved.
Extrusion–spheronization is a multistep process involving equipment like extruders and spheronizers, which consist of a feeding zone, a compression zone, and an extrusion zone, to produce desired pellet size.
Spray Drying and Spray Congealing
Spray drying and spray congealing, known as globulation processes, involve atomization of hot melts, solutions, or suspensions to generate spherical particles or pellets.
Cryopelletization is a process whereby droplets of a liquid formulation are converted into solid spherical particles or pellets by using liquid nitrogen as the fixing medium.
Melt spheronization is a process whereby a drug substance and excipients are converted into a molten or semi-molten state and subsequently shaped using appropriate equipment to provide solid spheres or pellets.
Spherical agglomeration, or balling, is a pelletization process in which powders, on addition of an appropriate quantity of liquid or when subjected to high temperatures, are converted to spherical particles by a continuous rolling or tumbling action.