Development of prolonged release hydrogel oral dosage form of Physostigmine

Alzheimer's disease (AD) is an insidious, degenerative, debilitating disease of the brain. AD is characterized by relentless, irreversible deterioration of intellect, cognition, emotions and behavior. Biochemically, deficits in a number of neurotransmitters and neuropeptides have been observed. The most consistent biochemical deficit observed is a decrease in acetylcholine levels. Current therapy has been directed to rectify this deficit found in the cholinergic system. One category of drugs tried is the cholinesterase inhibitors which prevent the breakdown of acetylcholine. Physostigmine (PSM) is an anticholinesterase that has shown encouraging results. The major problems associated with PSM are the need for frequent dosing due to PSM short half life and the high incidence of side effects due to PSM narrow therapeutic range. An oral prolonged release dosage form may help to alleviate these problems. Hydrogels are biocompatible polymeric materials which swell in water and other solvents, absorbing the fluid within the polymer network without dissolving themself. Hydrogels, copoly-merized from a neutral monomer, 2- hydroxyethyImethacrylate (HEMA), a monomer capable of becoming negatively charged, methacrylic acid (MAA), or N,N dimethylacrylamide (NND), a monomer capable of becoming positively charged, by free radical polymerization were investigated as prolonged release devices for PSM. [...]