Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Matrices
Reexamination Certificate
1998-02-20
2002-10-29
Webman, Edward J. (Department: 1617)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Matrices
C424S485000, C424S486000, C424S488000
Reexamination Certificate
active
06471992
ABSTRACT:
1. FILED OF THE INVENTION
The present invention relates to rapidly dispersing dosage forms, also known as “flash dose” dosage forms. In particular, the pharmaceutical compositions of the present invention release their active ingredients within a period of less than about ninety seconds and are suitable for administration to a subject via a variety of routes, preferably by insertion into a body cavity or application to a moist body surface or open wound. The invention also relates to methods of administration of a medicament and a process for the preparation of rapidly dispersing dosage forms.
2. BACKGROUND OF THE INVENTION
Tablets and pills are well known. They are generally the preferred vehicles for oral administration of both prescription and over the counter medications. There are certain situations, however, in which the use of tablets or pills is undesirable. For example, individuals with laryngeal inflammation or esophageal disorders may have difficulty swallowing. In other cases there is no liquid available to aid swallowing. Small children often find it difficult to swallow pills and/or may choke in the attempt. An alternative to tablets and pills is the use of liquid medicaments, e.g., elixirs and syrups. Liquid medicaments have their own drawbacks, however, including imprecise dose measurement and, in the case of oral administration to young children, loss of some or all of the medicament via deliberate or accidental rejection.
An ideal alternative would be a solid dosage form that can be administered orally, which rapidly disperses in the mouth, and hence does not require great effort in swallowing. Such an idealized approach minimizes the possibility of rejection, if administered to a young child, and yet remains stable in composition and structure over a reasonable period of time, i.e., has adequate shelf life. Suitable rapidly dispersing dosage forms could also be used in other applications, including the treatment of wounds and other bodily insults and diseased states in which release of the medicament by externally supplied moisture is not possible.
There have been prior attempts to make stable and quick dispersing dosage forms. Effervescent dosage forms and quick release coatings of insoluble microparticles are described in U.S. Pat. Nos. 5,578,322 and 5,607,697. Freeze dried foams and liquids are described in U.S. Pat. Nos. 4,642,903 and 5,631,023. Melt spinning of dosage forms is described in U.S. Pat. Nos. 4,855,326, 5,380,473 and 5,518,730. Each of these dosage forms has drawbacks that limit their usefulness.
In particular, effervescent dosage forms, while providing rapid dissolution, require that a combination of an acid and an alkali be used. This limits the type of active ingredients (i.e., medicaments) which can be incorporated in the dosage form to those which are insensitive to acid or alkali levels. Moreover, the coating of microparticles may affect the oral release of the microparticles themselves, but not necessarily the oral release of the free form of the medicament contained in the microparticles.
Freeze-drying is a complex process and limits the scope of suitable medicaments to those having good solubility and relatively low density. Freeze dried dosage forms are also fragile and, hence, may require special handling and packaging. On the other hand, melt spinning requires that both medicament and a carrier be forced at high temperature and pressure through a small orifice, which requires the use of highly heat stable medicaments and results in a malleable amorphous product best described as a wool or fiber.
An alternative manufacturing processes is solid, free-form fabrication (SFF), which is technique capable of creating complex structures via a layering process. One example of SFF is three-dimensional printing (3DP) which employs computer-aided design (CAD) to construct components in a sequential laminating process. U.S. Pat. No. 5,490,962 relates to the use of 3DP for the preparation of various medical devices. This patent is silent, however, and does not address the problems associated with oral administration under the situations described above, nor does it disclose, teach, or suggest the construction of rapidly dispersing dosage forms. It should be noted that this patent, as well as any other reference cited in the present specification, is incorporated by reference herein in its entirety.
Hence, there remains a need in the art for a convenient, pre-measured dosage form that is stable, and yet is suitable for oral administration to small children and others having difficulty in swallowing. There is also a need in the art for a dosage form suitable for placement in a non-oral body cavity, body surface, or exposed area which can effect rapid release of a medicament without the need of applying (i.e., without necessarily being accompanied by) externally supplied moisture. These needs are met by the dosage form of the present invention, as described further below.
3. SUMMARY OF THE INVENTION
It is accordingly an aspect of the invention to provide a rapidly dispersing dosage form suitable for placement in a body cavity, on a body surface or exposed area, such as an open wound.
It is another aspect of the invention to provide a rapidly dispersing dosage form that can disperse in less than about five minutes, preferably less than about ninety seconds, more preferably in less than about thirty seconds and most preferably in less than about ten or fifteen seconds.
It is yet another aspect of the invention to provide a rapidly dispersing dosage form that can incorporate a wide range of medicaments, and is not limited by processing considerations or composition requirements.
It is yet another aspect of the invention to provide a rapidly dispersing dosage form that can incorporate two or more medicaments either as a mixture or as separate domains within the dosage form.
It is yet another aspect of the invention to provide a rapidly dispersing dosage form having superior hardness and friability characteristics and which has a shelf life of at least about one year.
These aspects, and others set forth more fully below, including methods of administration of a medicament, processes for the preparation of certain rapidly dispersing dosage forms and drug delivery vehicles, are achieved by the present invention.
In particular, a rapidly dispersing dosage form is disclosed which comprises a solid matrix incorporating at least one active ingredient, the matrix having a three-dimensional structure suitable for administration to the subject, and wherein the matrix comprises a bulk material and a binder, the bulk material comprising at least one pharmaceutically acceptable compound in powder form, the binder comprising a substantially water-soluble pharmaceutically acceptable substance that together with the powdered compound allows the matrix to maintain its three-dimensional structure in the absence of excess moisture. The pharmaceutical composition of the present invention is designed to disintegrate with release of the one or more active ingredients within a time period ranging from about one to about ninety seconds after administration to the subject or upon contact with moisture. Such dosage forms also exhibit hardness and friability characteristics sufficient to provide a commercially acceptable shelf life, preferably a shelf life of at least about one year.
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patent: 5518730 (1996-05-01), Fuisz
patent: 5578322 (1996-11-01), Shiozawa et al.
patent: 5607697 (1997-03-01), Alkire et al.
patent: 5631023 (1997-05-01), Kearney et al.
patent: 5633021 (1997-05-01), Brown et al.
Kumar Sandeep
Monkhouse Donald C.
Yoo Jaedeok
Betcher Susan D.
Seed IP Law Group PLLC
Therics, Inc.
Webman Edward J.
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