Overview of contract drug product manufacturing services that enable the production of coated pellets & granules with varied release profiles.
Q1. What are granules & pellets?
Granules
Granules are aggregations of fine particles of powder, drugs and excipients, bound together by binding agents into larger, free-flowing irregularly shaped spherical masses, which typically fall within 850 µm to 4.75 mm in size. Granules flow better than powders, increase compressibility, and have smaller surface areas than comparable volumes of unaggregated powders.
Furthermore, granules are produced to enhance the uniformity of the API in the final product, to increase the density of the blend so that it occupies less volume per unit weight for better storage and shipment, to facilitate metering or volumetric dispensing, to reduce dust during the granulation process in order to reduce toxic exposure and process-related hazards, and to improve the appearance of the product.
The process termed granulation, transforms fine powders into free-flowing, dust-free granules by using techniques such as extrusion granulation, wet granulation & dry granulation amongst others. After granulation, the granules are either packaged or mixed with other excipients prior to tablet compaction or capsule filling.
Granules can be divided into three distinct types:
(I) Sustained Release Granules
Sustained release granulated dosage forms are designed to release a drug at a predetermined rate in order to maintain a constant drug concentration for a specific period of time with minimum side effects and long term action.
(II) Enteric Coated Granules
Enteric coated granules are coated in enteric release coatings. This type of coating serves as a barrier on the surface of oral solid medications by protecting them from the acidic pH (i.e. acidity) of the stomach, thereby preventing dissolution.
(III) Effervescent Granules
Effervescent granules are granular finished dosage forms comprising a drug and an effervescent base which is composed of sodium bicarbonate, citric acid and tartaric acid. When added to water, the acids and the base react to liberate CO2, resulting in effervescence.
Pellets
Pharmaceutical pellets are agglomerates made from fine powder particles, characterized by a nearly spherical or cylindrical shape, mean diameters of 0.2-2.0 mm and a narrow particle size distribution. The surface of pellets is typically smooth and of low porosity.
Pharmaceutical pellets are multiparticulates created by the agglomeration of fine powdered excipients and drugs into small, free flowing, uniformly sized spheroids or semi spherical particles. The formulation development of pellets is important as pellets disperse freely in the GI tract, maximize drug absorption, and minimize local irritation of the mucosa by certain irritant drugs.
There are several pelletization techniques used for manufacturing pellets. Amongst them, agglomeration through extrusion and spheronization is the most widely used development process to form pellets. This pellet technology (bead technology) is explored further in question 3.
Some types of pharmaceutical pellets:
(I) Controlled Release Pellets (controlled release multiple unit dosage forms)
Different pellets with different release profiles can be combined together and co-administered in order to get controlled release capabilities, and are known as controlled release pellets.
(II) Immediate Release Pellets
Immediate release pellets dissolve in the body quickly after administration resulting in faster onset of action.
(III) Complex modified release pellets / Enteric coated pellets
Most enteric coatings work by presenting a surface that is stable at the highly acidic pH found in the stomach, but breaks down rapidly at a less acidic (relatively more basic) pH. Therefore, enteric coated pellets have complex modified release dosage form capabilities developed through modified release technologies.
After the formulation development and manufacturing of granules and pellets is complete, granules and pellets are processed effectively into oral solid finished dosages, such as tablets and capsules, or into multiparticulates such as enteric coated pellets & coated granules, etc. This is achieved via pharmaceutical formulation development services and advanced manufacturing capabilities offered by contract development and manufacturing organizations (CDMOs) or contract manufacturing organizations (CMOs).
Q2. What are the different types of pellet technologies and what are their benefits?
Pellets are small, free flowing spherical particles manufactured by the agglomeration of fine powder or granules. Different types of pharma pelleting technology and processes are used to produce pellets.
Pellet or bead technology is a drug development pharmaceutical CDMO technology that allows a variety of different drug delivery systems with varied release profiles to be achieved by coating ‘core pellets’ with various polymers.
Depending on the type of polymers used various profiles can be achieved such as controlled release formulations, targeted drug delivery systems, complex modified release finished dosage forms (using modified release technologies), etc.
Some important pharma pelleting technology and processes are explored below:
Cryopelletization:
Cryopelletization is a process whereby droplets of a liquid are converted into solid spherical particles or pharmaceutical pellets by using liquid nitrogen as the fixing medium. This technique is usually used to produce drug loaded pellets for immediate release as well as controlled release multiple unit dosage forms known as controlled release pellets.
Hot Melt Extrusion:
Hot-melt extrusion (HME) bead technology converts powders/raw materials into uniformly shaped, dense pellets by forcing them through a die under controlled conditions. Hot-melt extrusion can create pellets wi