Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Reexamination Certificate
1998-12-21
2001-05-29
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
C424S465000, C424S469000, C424S470000
Reexamination Certificate
active
06238697
ABSTRACT:
BACKGROUND OF THE INVENTION
Pharmaceutical manufacturers are continuously attempting to improve methods for delivering drugs to enhance and sustain their effects in human therapy. A significant development in drug delivery systems occurred in 1972 with the development of osmotic delivery systems as described by U.S. Pat. Nos. 3,845,770 and 3,916,899. Modifications to the rate-controlling osmotic delivery systems of the prior art are also disclosed in U.S. Pat. Nos. 4,816,263 and 4,902,514.
Such modified osmotic delivery systems use a semi-permeable wall to surround an interior containing the drug to be delivered. The external wall is permeable to the passage of an external fluid and may not be permeable to the drug. Such systems may include at least one outlet in the wall for delivering the drug through the osmotic system. The systems operate by absorbing gastric fluid through the semi-permeable wall into the interior of the dosage form at a rate determined by the permeability of the semi-permeable wall and the osmotic pressure gradient across the semi-permeable wall. The absorbed fluid produces an aqueous solution containing the drug that is then delivered to the body through at least one opening in the wall.
U.S. Pat. No. 4,816,263 discloses an osmotic device form for delivering isradipine to a biological receptor site in a rate-controlled amount over a prolonged period for cardiovascular therapy. The pharmaceutical dosage form adapted, designed, and shaped as an osmotic drug delivery system is manufactured by wet granulation and includes two compositions which form a bi-layered tablet coated by a semi-permeable wall. The first composition includes the drug and contains polyethylene oxide having a molecular weight of 200,000 which is screened through a 40 mesh screen. Specific amounts of isradipine and hydroxypropyl methylcellulose having a molecular weight of 11,200 are added to the polyethylene oxide and slowly mixed with denatured, anhydrous ethanol using a conventional mixer. The wet granulation formed is then passed through a 20 mesh screen, dried at room temperature and passed through the 20 mesh screen again. Magnesium stearate is then added to the granulation and mixed in a roller mill.
The second composition used in the osmotic device is prepared by mixing polyethylene oxide of molecular weight 7,500,000 with sodium chloride in a blender to form a homogeneous blend. The blend is passed through a 40 mesh screen. The mixture is then mixed with a specific amount of hydroxypropyl methylcellulose having a molecular weight of 11,200 and with a specific weight of ferric oxide. Denatured, anhydrous ethanol is slowly added to the blended mixture while mixing again before the wet granulation is screened through a 20 mesh screen. A bi-layered press is used to compress the granulation into two-layered tablets. The tablet is surrounded with a semipermeable wall including 97% cellulose acetate and 3% polyethylene glycol of molecular weight of 3,350. The wall forming composition is dissolved in methylene chloride and methanol to make a 4% solids solution. The wall forming composition is sprayed onto and around the bilaminate in an Aeromatic Air Suspension Coater. The coated tablet is then dried. A 25 mm exit orifice is laser drilled on the laminate side of the osmotic device.
A dosage form for delivering and administering nilvadipine for treating cardiovascular symptoms in a rate-controlled dose over a period of time was developed as described in U.S. Pat. No. 4,902,514. This patent is directed to providing a dosage form manufactured as an osmotic agent that substantially reduces and/or eliminates the unwanted influence of the gastrointestinal environment and still provides controlled administration of nilvadipine over time. The device includes an insoluble coating enclosing the interior within the dosage form. The coating of the dosage form is permeable to the inward passage of exterior fluid present in the gastrointestinal tract into the interior of the dosage form.
In 1987, Urquhart et al. developed an extended-release drug delivery system for delivering a quantity of tiny pills to the gastrointestinal tract. The system includes a pharmaceutical oral capsule prepared with a drug carrier formed of an aqueous polymer and oil capable of controlling the rate of transit of the capsule and the release of the drug from the capsule to the gastrointestinal tract.
Products formulated for controlled-release are generally described as sustained release, prolonged action, depot, repository, delayed-action, retarded-release, and timed-release. Drug products which are formulated for prolonging absorption include dosage forms for oral, injectable and topical use as well as suppositories for insertion in the body cavities. Extended-release tablets are defined herein as pharmaceutical solid dosage forms containing drug substances which are released from the tablet or delivery system over an extended period of time using specific ingredients and includes mechanisms as discussed above such as timed-release, intermittent release and retarded release. They are produced by compression of a formulation containing the drug and certain excipients selected to aid in the processing and release of the drugs. Excipients are classified in accordance with their intended function. Exemplary components for such formulations include fillers, binders, lubricants, and glidants. Without excipients, most drugs and pharmaceutical components cannot be directly compressed into tablets primarily due to the poor flow and/or cohesive properties of most drugs. Extended-release tablets may be coated or uncoated, and are generally formed of powdered, crystalline materials.
Drugs can be administered from a delivery system that releases the drug as it passes through the gastrointestinal tract. Extended-release delivery systems are used because they eliminate the need for multiple dosing. The convenience of extended-release preparations which maintain the blood concentration of the drug at a desired level over a prolonged period of time has been recognized. Extended-release preparations such as a slow-release matrix type tablet in which the ingredients are embedded in a matrix, such as polymeric resins, release the active ingredient by diffusion and erosion.
Most extended-release forms are designed so that the administration of a single dosage unit provides the immediate release of an amount of drug that promptly produces the desired therapeutic effect as well as a gradual and continual release of additional amounts of drug to maintain this level of effect over an extended period of time. In this type of dosage form, the design is based on the particular qualities of each individual drug.
What may be an effective type of dosage form design for one drug may be ineffective in promoting the extended-release of another drug because of peculiar physical, chemical and biological qualities of the different drugs. To maintain a constant level of drug in the system, the drug must be released from the dosage form at a rate that will replace the amount of drug being metabolized and excreted from the body.
Other advantages of extended-release products are reduced side effects and increased patient convenience. These advantages relate to the fact that extended-release preparations maintain the blood concentration of the drug at a desired level over a prolonged period of time which allows patients to reduce the frequency of dosing. This is considered an advantage in ensuring patient compliance in taking medication. Patients required to take one or two dosage units a day are less likely to forget their medication than if they are required to take their medications three or four times a day.
Therefore, there is a need in the art for a drug delivery system that has a sufficiently long transit time in the stomach and acts as an in vivo reservoir, and which releases the drug at a controlled rate and continuously over a prolonged period of time for absorption in the stomach and the intestine.
The method of preparation and type of excipients used
Kumar Vijai
McGuffy Kevin Scott
Matalon Jack
Page Thurman K.
Pharmalogix, Inc.
Ware Todd D
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