Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Reexamination Certificate
1997-04-28
2001-04-03
Spear, James M. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
C424S435000, C424S451000, C424S455000, C424S456000, C424S470000, C424S468000, C514S770000, C514S772300, C514S777000, C514S778000, C514S779000, C514S780000, C514S781000, C514S782000, C514S784000
Reexamination Certificate
active
06210710
ABSTRACT:
This invention relates to a sustained release composition, and, more particularly, to a pharmaceutical composition having a polymer blend that will release a therapeutic agent for a prolonged or sustained period of time.
BACKGROUND OF THE INVENTION
Controlled or sustained release dosage forms are well known in the prior art and make broad use of polymeric compositions to delay or control the release of a medicament or nutritional supplement. Controlled or sustained release dosage forms are desirable because they provide a single dosage application without overdosing the patient and deliver a medicament or nutritional supplement at an appropriate rate to provide the desired activity over periods of time of up to 24 hours. These dosage forms can be formulated into a variety of physical structures or forms, including tablets, lozenges, gelcaps, buccal patches, suspensions, solutions, gels, etc.
Polymer blends in sustained release compositions are known and used in the pharmaceutical industry because of the blend's versatility of being able to create different release profiles. Cellulose ethers are desirable polymers for use in sustained release compositions because they are derived from naturally occurring cellulose, and are free-flowing, readily compressible powders. Unfortunately, not all cellulose ethers provide a desirable release profile for compressed tablets.
Many approaches are disclosed in the prior art for creating blends with unique characteristics. Blending of hydroxypropylmethylcellulose (HPMC) with other polysaccharides is a common blending approach as seen in the prior art. Two examples of this approach are disclosed in U.S. Pat. Nos. 4,389,393 that discloses HPMC and carboxymethylcellulose (CMC) blends and 4,756,911 that discloses HPMC and guar gum blends. Another blending approach is disclosed in U.S. Pat. No. 5,451,409 that blends hydroxypropylcellulose (HPC) with hydroxyethylcellulose (HEC) for use as sustained release pharmaceutical matrix compositions. U.S. Pat. No. 4,704,285 discloses the use of fine particle size HPC alone or blended with HPMC for sustained release applications; U.S. Pat. No. 4,259,314 also discloses the use of the blend of HPMC and HPC with both hygroscopic and non-hygroscopic materials.
Although many different approaches are disclosed in the prior art for creating blends of cellulose ethers, a need still exists in the pharmaceutical industry for having additional cellulose ether polymeric materials that would provide additional flexibility in sufficient release profiles that are stable yet economical for compressed tablets. In addition to providing the desired release rate profile, the polymeric composition should also provide required material properties to the dosage form for safe use and consistent manufacture.
SUMMARY OF THE INVENTION
The present invention is directed to a sustained release pharmaceutical composition comprising a polymer blend formed with a medicament present in a therapeutic amount where the polymer blend contains at least a first component and a second component. The first component is selected from the group consisting of HPC, ethyl cellulose (EC), and derivatives of HPC, EC, and HEC and the second component is at least one other polymer with the proviso that when HPC is the first component, HPMC, HEC or CMC will not be the second component. Another proviso is when EC is the first component, HPMC will not be the second component. A medicament is present in sufficient amount to be therapeutic.
DETAILED DESCRIPTION OF THE INVENTION
It has now been found that the sustained or extended release dosage forms of the present invention make broad use of polymeric compositions to delay or control the release rate of a medicament or nutritional supplement creating a wide range of release profiles for a wide range of medicaments. Through the blending of a wide range of polymers, it is possible to produce equivalent or enhanced tableting performance as well as enhanced sustained or controlled release properties to a wide range of medicaments. The polymeric blends of the present invention, not only improve sustained release characteristics when compared to the individual polymers, but in most cases, in tablet form have shown improved tablet hardness, improved tablet friability and a more manageable and predictable granulation endpoint.
The pharmaceutical compositions of this invention include blends of hydroxypropyl cellulose (HPC), ethyl cellulose (EC) or derivatives of HPC, EC, or HEC with other polysaccharides and their derivatives and synthetic polymers.
This invention provides a controlled or sustained release of a wide range of medicaments or nutritional supplements as well as provides a wide range of material properties to the dosage forms in which they are included. The blend of this invention contains at least two components while three or four or even five components can be used with the number of components being determined primarily by the desired release profile, desired characteristics of the dosage form, and the properties of the drugs.
According to the present invention, the components of the blend are preferably selected so that a dosage form releases the medicament drugs over precise periods of time. The blend in the composition of the present invention should be sufficient to provide the sustained release effect. Typically, the blend should be greater than 5% by weight of the composition of the present invention. Preferably, the blend should be greater than 15%, more preferably greater than 20% with the maximum being dependent upon the drug properties and release profile. A 30% blend is a preferable blend. The upper limit of the amount of the blend in the composition can be 99%, but preferably 95%, and more preferably, 90% dry weight of the composition.
Although a number of polymers may be used in the matrix blend of the present invention, this invention particularly contemplates the use of combinations of either HPC or EC or derivatives of HPC, EC or HEC as the first component with at least one other polymer. A proviso is that HPC cannot be used with HEC, is CMC or HPMC and EC cannot be used with HPMC.
Examples of derivatives of HPC or EC that are useful in the practice of the present invention are anionic modifications, such as carboxymethyl moiety, cationic modifications, such as hydroxypropyltrimethylammonium salts, and nonionic modifications, such as alkyl or arylakyl moiety having 2 to 30 carbons.
Examples of polysaccharides useful in the practice of the present invention are carboxymethylcellulose (CMC), hydroxyethylcellulose (HEC), methylcellulose (MC), ethylhydroxyethylcellulose (EHEC), hydroxyethylmethylcellulose HEMC), hydrophobically modified hydroxyethylcellulose (HMHEC), hydrophobically modified ethylhydroxyethylcellulose (HMEHEC), carboxymethylhydroxyethylcellulose (CMHEC), carboxymethyl hydrophobically modified hydroxyethylcellulose (CMHMHEC), guar and guar derivatives, pectin, carrageenan, xanthan gum, locust bean gum, agar, algin and its derivatives, gellan gum, acacia, starch and modified starches; examples of synthetic polymers are mono- and co-polymers of carboxyvinyl monomers, mono- and co-polymers of acrylates or methacrylates monomers, mono- and co-polymers of oxyethylene, or oxypropylene monomers. All of these second and subsequent components can be used either alone or as mixtures thereof.
According to the present invention, the ratio of the HPC or EC or derivatives of HPC, EC, or HEC to the total amount of the other polymer components in an uncoated dosage form should be in the range of from about 1:99 to 99:1 where the total of these components equals 100 weight percent. A preferred range is 5:95 to 95:1 with a more preferred range being 10:90 to 90:10. Preferred blends are HPC/CMC, HPC/guar, HPC/carboxyvinyl polymer, HPC/carrageenan, and ethyl cellulose/guar. The more preferred blends are those with HPC being the first component.
One or more medicaments may be combined in a single dosage form, depending on the chemical compatibility of the combined active ingredients and the
Edwards David
Hercules Incorporated
Sloan Martin F.
Spear James M.
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