Dual drug dosage forms with improved separation of drugs

a drug and dosage form technology, applied in the field of drug dosage forms, can solve the problems of swelling of the outer surface of the prolonged-release portion, difficulty in complying with such a schedule without the assistance of patients, and difficulty in maintaining dosage therapies such as these, so as to reduce or prevent any drug migration, reduce or eliminate any penetration

Inactive Publication Date: 2005-01-20
DEPOMED SYST INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0006] It has now been discovered that a drug dosage form that includes a prolonged-release core and an immediate-release layer or shell can be manufactured in a manner that reduces or prevents any migration of drug from the immediate-release portion into the prolonged-release portion, by interposing a thin protective layer of drug-free polymer between the prolonged-release and immediate-release portions. The protective layer is penetrable by, or dissolved in, water or gastrointestinal fluid, thereby providing full access of the gastrointestinal fluid to the prolonged-release core. The protective layer remains intact however during the application of the immediate-release layer, substantially reducing or eliminating any penetration by the immediate-release drug. The protective layer thereby allows immediate release of the entire dose of drug in the outer layer. The inclusion of the protective layer also serves to prevent interaction of the prolonged-release and immediate-release drugs, which is of value in cases where interaction between the two drugs may be detrimental to the activity of either or both of the drugs.

Problems solved by technology

While this can be accomplished if the administration is done according to a strict time schedule, many patients have difficulty complying with such a schedule without the assistance of a medical professional.
Even two-dosage therapies such as these however can be troublesome to maintain if a separate administration is needed for each dosage.
In some cases, however, the liquid carrier tends to cause swelling of the outer surface of the prolonged-release portion.
When the immediate-release drug is applied as a suspension of particles, the particles tend to become trapped in the prolonged-release matrix.
The problem can be particularly acute when the drug is insoluble or of low solubility, since unintended retention of the drug in the prolonged-release portion can significantly reduce the amount of the drug that is available for absorption into the patient's bloodstream.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

[0042] This example illustrates the preparation of tablets in accordance with this invention that contain 500 mg metformin hydrochloride as the prolonged-release component and 1 mg glimepiride as the immediate-release component.

[0043] Pre-formed tablets containing 500 mg of metformin hydrochloride in a matrix of hydroxypropyl methyl cellulose, poly(ethylene oxide), microcrystalline cellulose, and magnesium stearate were used as a starting material. A barrier layer solution was prepared by dissolving OPADRY® YS-1-19025-A Clear (“OPADRY Clear,” hydroxypropyl methyl cellulose, available from Colorcon, West Point, Pa., USA) in purified water to a concentration of 8 weight percent. This solution was sprayed onto the metformin hydrochloride tablets until the tablet weight increased by approximately 1%.

[0044] A suspension for applying the immediate-release layer was prepared by dissolving polyethylene sorbitan monooleate in purified water, dispersing glimepiride (micronized, 2-4 micron a...

example 2

[0045] This example likewise illustrates the preparation of tablets in accordance with this invention that contain metformin hydrochloride as the prolonged-release component and glimepiride as the immediate-release component, but with a higher amount of glimepiride (2 mg) than Example 1.

[0046] Pre-formed metformin hydrochloride tablets identical to those used as a starting material in Example 1 were used. Likewise, an identical Opadry solution was used as the barrier layer solution. This solution was sprayed onto the tablets to achieve a weight increase of 1%.

[0047] To prepare the immediate-release layer, a suspension similar to that of Example 1 was prepared except that it contained 0.40% glimepiride rather than 0.20%. The suspension was sprayed onto the barrier layer until the tablet weight increased by approximately 4%.

example 3

[0048] This example illustrates the preparation of tablets in accordance with this invention that contain 500 mg metformin hydrochloride as the prolonged-release component and 2 mg glimepiride as the immediate-release component, but using a poly(vinyl alcohol)-poly(ethylene oxide) poly(ethylene oxide) both as the barrier layer and as a component in the immediate-release layer. The poly(vinyl alcohol)-poly(ethylene oxide) used in the barrier layer is KOLLICOAT® IR, a product available from BASF Corporation, Chemicals Division, Wyandotte, Mich., USA.

[0049] Pre-formed metformin hydrochloride tablets identical to those used as a starting material in the preceding examples are used. The barrier layer solution is then prepared by dissolving the KOLLICOAT IR in purified water to a concentration of 8% by weight. This solution is then sprayed onto the pre-formed tablets to achieve a weight increase of 1%.

[0050] The immediate-release drug-containing coating suspension is prepared by dissolv...

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Abstract

Drug tablets that include a prolonged-release core and an immediate-release layer or shell are prepared with a thin barrier layer of drug-free polymer between the prolonged-release and immediate-release portions of the tablet. The barrier layer is penetrable by gastrointestinal fluid, thereby providing full access of the gastrointestinal fluid to the prolonged-release core, but remains intact during the application of the immediate-release layer, substantially reducing or eliminating any penetration of the immediate-release drug into the prolonged-release portion.

Description

BACKGROUND OF THE INVENTION [0001] 1. Field of the Invention [0002] This invention is in the field of pharmacology, and relates to drug dosage forms that are designed to deliver drugs concurrently in both immediate-release and prolonged-release delivery profiles. [0003] 2. Description of the Prior Art [0004] Certain pharmacological therapies either require or benefit from the sequential administration of two or more drugs. While this can be accomplished if the administration is done according to a strict time schedule, many patients have difficulty complying with such a schedule without the assistance of a medical professional. Some therapies involve only an immediate but rapidly declining high-level dosage and a prolonged dosage at a low or moderate level, the two dosages being either of the same drug or of a different drug. Even two-dosage therapies such as these however can be troublesome to maintain if a separate administration is needed for each dosage. Certain pharmaceutical f...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K9/22A61K9/24
CPCA61K9/0065A61K9/209A61K31/00A61K45/06A61K9/2027A61K9/2054A61K9/2031A61K31/4415A61K31/4015A61K31/40A61K31/155A61K2300/00A61P7/10A61P9/12A61P43/00A61K9/20A61K9/2018A61K9/2077A61K9/2853
Inventor LIM, JONGSHELL, JOHN N.LOUIE-HELM, JENNY
Owner DEPOMED SYST INC
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