nems. spherical hydrogels, in micro-size (50-600 µm diameter) with 3-dimensional cross-linked polymer, can be used as drug carrier to control the release of the drug. these hydrogels are called microgels. they may possess a negative charge as example dc-beads. by ion-exchange mechanism, a large amount of oppositely charged amphiphilic drugs can be loaded inside these microgels. then, the release of these drugs can be controlled by a specific triggering factor like ph, ionic strength or temperature. pill splitting empty half-shell of a split bupropion xl 150mg manufactured by anchen pharmaceuticals that was soaked in water overnight and then shaken. some time release formulations do not work properly if split, such as controlled-release tablet coatings, while other formulations such as micro-encapsulation still work if the microcapsules inside are swallowed whole. among the health information technology (hit) that pharmacists use are medication safety tools to help manage this problem. for example, the ismp "do not crush" list can be entered into the system so that warning stickers can be printed at the point of dispensing, to be stuck on the pill bottle. pharmaceutical companies that do not supply a range of half-dose and quarter-dose versions of time-release tablets can make it difficult for patients to be slowly tapered off their drugs. history the earliest sr drugs are associated with a patent in 1938 by israel lipowski, who coated pellets which led to coating particles. the science of controlled release developed further with more oral sustained-release products in the late 1940s and early 1950s, the development of controlled release of marine anti-foulants in the 1950s, and controlled release fertilizer in the 1970s where sustained and controlled delivery of nutrients was achieved following a single application to the soil. delivery is usually effected by dissolution, degradation, or disintegration of an excipient in which the active compound is formulated. enteric coating and other encapsulation technologies can further modify release profiles.