Oral drug-delivery systems are the most acceptable form of controlled-release system to patients. Scientists have shown growing interest in modified-release oral dosage forms in recent years. Current technologies, such as oral multiparticulate drug-delivery systems (MDDS), have gained immensely in importance, not only because of their ability to control drug release, but also for the modified drug-release profiles they facilitate.
These systems release the drug with constant or variable release rates, thus maintaining drug concentration within the therapeutic window for a prolonged period of time. The desired release profile facilitates controlled absorption through the target site in the body, ensures good therapeutic activity, and reduces side effects (1). MDDS comprises a large number of small discrete particles (i.e., active ingredient and excipients), each demonstrating desirable features. They are prepared by methods including extrusion–spheronization, pelletization, granulation, spray drying, and spray congealing.
Multiunit particulate systemsMultiunit particulate systems (MUPS) are a novel MDDS technique for controlled and modified drug delivery. MUPS offer various advantages over other systems, including reduced risk of local irritation and toxicity, predictable bioavailability, reduced likelihood of dose dumping, minimized fluctuations in plasma concentration of drug, and high dose-strength administration (1). Multiparticulate systems show more reproducible pharmacokinetic behavior and lower intra- and intersubject variability than conventional (i.e., monolithic) formulations (2). Tableting of pellets reduces the esophageal residence time, compared with capsules, and improves physicochemical stability, compared with suspensions (2, 3).
The applications for which MUPS formulations are developed include taste masking (i.e., orodispersible MUPS tablets), enteric-release (e.g., of acid-labile drugs), and modified- or controlled-release orodispersible drugs for geriatric or pediatric patients. The technology of preparing compacted MUPS ensures that the desired objectives (e.g., taste masking coupled with orodispersibility as well as modified-release characteristics) are effectively achieved.
A good example of a MUPS is AstraZeneca's Losec, an antiulcer drug, the second-highest-selling pharmaceutical product in Sweden in 2002 (3). The product consists of microencapsulated drug granules tableted with excipients (4). Other marketed MUPS formulations include Galanil PR (Galantamine HBr) for Alzheimer's disease, antiobesity drug Lipidown (Orilistat), and Esomezol (Esomeprazole Sr) for erosive reflux esophagitis, which are all manufactured by Hanmi Pharmaceutical.
Challenges in the formulation of multiunit particulate systems
Each discrete particle in a MUPS product incorporates its own release characteristics and further contributes to the product's therapeutic activity. Compressing these subunits without affecting their individual release profiles is a major challenge of MUPS technology because compacting subunits may lead to structural changes in the coating and consequently alter drug-release behavior (5).
Other challenges for manufacturing pellets in tablets (i.e., MUPS) are weight variation, poor hardness, and friability. To prevent subunits from being altered, formulators include a cushioning agent (i.e., an excipient with protective properties) in the tablet formulation.
Pelletization and multiunit particulate systems