Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Reexamination Certificate
1999-06-01
2001-04-10
Spear, James M. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
C424S422000, C424S423000, C424S430000, C424S433000, C424S434000, C424S436000, C424S441000, C424S443000, C424S451000, C424S455000, C424S456000, C424S458000, C424S463000, C424S468000, C424S472000, C424S474000, C424S489000, C424S490000, C514S937000
Reexamination Certificate
active
06214379
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to novel dosage forms, drug delivery regimens, methods and compositions which optimize therapeutic effects of biologically useful substances. The dosage forms, regimens, methods and pharmaceutical compositions of the present invention are adaptable to most biologically useful substances and will improve the effectiveness of said substances. The present invention is particularly useful for adaptation to the schedules, cycles and needs of individuals, thereby frequently improving compliance with their therapy, reducing amounts required daily to less than conventionally utilized, and minimizing undesired effects commonly experienced.
DESCRIPTION OF THE PRIOR ART
The administration of a substance to achieve a therapeutic objective generally requires the attainment and maintenance of a biologic response, which in turn requires an appropriate concentration of the active substance at a site of action. The appropriate dosage needed to achieve a therapeutic objective largely depends upon factors specific to the individual being treated, such as the individual's clinical state, the severity of the condition being treated, and the presence of other drugs and concurrent disease. Further, a proper dosage also depends upon factors specific to the individual substance being administered. These drug specific factors are characterized through two concepts: pharmacodynamics and pharmacokinetics.
Pharmacodynamics refers to the biologic response observed relative to the concentration at the active site. Pharmacokinetics refers to the attainment and maintenance of the appropriate concentration. Generally, once an individual's condition has been assessed and a substance is chosen for administration, a dosage amount will be selected by taking into consideration the known pharmacokinetic parameters of the substance in view of the individual's specific needs.
A substance may be administered to the individual in a number of dosage forms. For example, the dosage may be administered as a single dose in a given 24 hour period, in multiple doses throughout a 24 hour period, e.g., once a day, twice a day, or three times a day. Further, the dosage may be administered in immediate release, controlled release, sustained release, timed release, delayed release, extended release, long acting and other such forms. Regardless of which of the above forms is employed, presently used dosage forms generally fail to account for the effects of administration between time intervals of differing lengths, the time at which doses are administered, and the varying physiological needs of individuals throughout the course of a day.
For example, a common dosing regimen described in the medical literature is the 9-1-5-9 regimen in which equal doses of a drug are administered once every four hours during the 12 daylight hours of a 24 hour period (e.g., at 9:00 am, 1:00 pm, 5:00 pm and 9:00 pm), and no doses are administered during the following 12 nighttime hours. See
The Merck Manual,
Sixteenth Edition, 277:2623 (1992). Therefore, in the 9-1-5-9 regimen, an individual will receive the same amount of active therapeutic substance at 9:00 pm as at each of the other administrations, despite the substantially longer time interval of 8 hours following the 9:00 pm administration relative to the 4 hour time intervals following the other administrations.
Another common dosing regimen is that in which an individual takes one dose upon awakening and a second dose upon retiring. In this common twice-a-day regimen, sixteen hours may elapse between the daytime dose (6:00 AM to 10:00 PM) and only eight hours (10:00 PM to 6:00 AM) until the next dose is taken upon arising the next morning. Therefore, the individual will have either too high a dose during the night, or too low a dose during the day because the doses are equal.
Currently employed dosage forms, such as the ones described above, are problematic for a number of reasons. First, the administration of equal doses for time intervals of differing lengths results in levels of active therapeutic substance at the site of action which may be alternatively too high or too low to maintain therapeutic effectiveness over a given period of time.
Secondly, the currently employed dosage forms involve the administration of even doses at uneven time intervals thereby failing to account for physiological anomalies which occur throughout the course of a given 24 hour period. For example, conventional dosage forms fail to recognize the difference in an individual's metabolic rate during that individual's sleeping and waking hours.
Thirdly, currently used dosage forms will generally result in the administration of higher amounts of drug to a patient over a given period of time, which will in turn result in increased incidents of side effects. Further, as the body adapts to the presence of the higher amounts of active therapeutic substance, said therapeutic substance will likely be less efficacious.
Fourthly, currently used dosage forms fail to factor into consideration the effects of the varying solubilities of their components. For example, in currently employed drug dosage forms a therapeutic substance containing a water-soluble component and a non water-soluble component would have equal amounts of water-soluble component present in each dose. Therefore, a tablet to be administered just prior to bedtime, for example, would contain the same dose of water-soluble substance as a tablet to be administered in the morning dose. Such a dosing form fails to account for the specific absorption of each component at various times and again may result in levels of active therapeutic substance at the site of action which are either too high or too low at various times throughout a given 24 hour period.
In addition to the importance of the dosage forms for maintaining therapeutically effective drug levels at the site of action, the success of a dosing form in achieving its therapeutic objective is largely dependent upon an individual's compliance with his or her drug dosing regimen. A individual's failure to comply with a dosing regimen, e.g. failure to take one or more doses of a drug or taking too many doses, will have an adverse impact upon the success of the regimen. Individuals may fail to comply with their drug dosing regimen for a number of reasons. For example, drug dosing regimens, such as the 9-1-5-9 regimen described above involve a rigid dosing schedule that may be incompatible with an individual's personal schedule. Such a rigid dosing schedule when combined with normal human traits such as forgetfulness or denial of medical condition, as well as a busy life, represent substantial obstacles to compliance with a drug dosing regimen. Accordingly, such rigid dosing regimens often result in the failure by an individual to take one or more doses at the prescribed time. This has an adverse impact on the levels of the therapeutic substance at the active site and consequently on the overall efficacy of the therapeutic substance.
Methods for optimizing the therapeutic effects of therapeutic substances by improving patient compliance with dosage regimens have been described. York, U.S. Pat. No. 5,521,208, describes novel compositions containing non-racemic mixtures of enantiomers tailored specifically to allow less frequent dosing and thus a more convenient dosing regimen to improve patient compliance of metabolically impaired individuals, such as individuals suffering from diabetes mellitus.
Lieberman et al., U.S. Pat. No. 5,597,072, describe a totally interactive patient compliance method which encourages compliance by a patient with their drug therapy by requiring that the patient call a phone number to obtain a code which will allow the patient to remove their medication from a specially designed dispenser and by recording each such phone call to signal that the patient has complied with the regimen.
Batchelor, U.S. Pat. No. 4,889,238, discloses a medicament package designed to improve compliance with a complex therapeut
K-V Pharmaceutical Company
Nath Gary M.
Nath & Associates PLLC
Spear James M.
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