For many tablets, particularly coated controlled, modified or delayed release prescription medication tablets, the drug release profile is altered or compromised upon breaking or splitting. Generally, single unit coated tablets cannot be broken into small pieces without compromising the coating. Such compromises result in differences in drug release profile rendering breaking or sprinkling of the tablet or capsule unacceptable. Thus, the American Medical Society and American Pharmacists Association recommends against splitting tablets that are modified release, combination products, unscored, film coated, friable or dose critical (Noviasky et al. The Journal of Family Practice, jfponline with the extension .com/Pages.asp?AID=4326 of the World Wide Web).
Many orally administered tablet preparations are coated either to achieve specific release profile or due to the rapid degradation of the drug in the acidic conditions of the stomach. Enteric protection is most commonly used to safeguard the drug from the acidic conditions of the stomach and is achieved by formulating enteric-coated granules within capsules, enteric-coated tablets, and enteric-coated multiple-unit pellet system commonly referred to as MUPS compressed into tablets.
For example, Omeprazole magnesium tablets manufactured by AstraZeneca (Prilosec OTC) are formulated as a “multiple unit pellet system” (MUPS). Essentially, the tablet consists of extremely small enteric-coated granules (pellets) of Omeprazole magnesium compressed into tablets using acceptable pharmaceutical excipients.
Information from clinical trials in patients with duodenal ulcers in remission indicates that the enteric coated Omeprazole magnesium 20 mg tablets (as a single unit formulation) and Omeprazole magnesium 20 mg capsules (as a multiple unit formulation) are not bioequivalent in terms of plasma AUC, Cmax and tmax. The enteric coated Omeprazole magnesium 20 mg tablets demonstrate, after repeated dosing, increased plasma Omeprazole AUC (18%) and maximum concentration (41%) in comparison to Omeprazole magnesium 20 mg given as capsules (as a multiple unit formulation).
Such differences in the pharmacokinetic parameters make substituting multiple unit pellet formulations of a drug with a single unit tablet formulation of the same drug extremely difficult.
USPTO Backgrounds
USPTO Backgrounds