Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2001-03-16
2003-05-06
Raymond, Richard L. (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C536S030000, C536S095000
Reexamination Certificate
active
06559134
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a solid preparation which disintegrates rapidly in the oral cavity with saliva or a small amount of water.
2. Description of the Related Art
In recent years, there is a demand for the development of an easily-taken and easily-administrable solid preparation for aged or pediatric patients who have difficulty in swallowing. Specific examples of such a solid preparation include orally disintegrating preparations, jellied preparations and paste preparations. Among them, orally disintegrating preparations can be taken conveniently and comparatively easily without water or with a small amount of water so that it can be a dosage form suited for the aged or infant.
A variety of orally disintegrating preparations have so far been proposed. For example, an orally disintegrating tablet prepared by filling PTP (Press Through Package) with an aqueous solution of an active ingredient and a polymer such as gelatin and then lyophilizing it, and a production process thereof are proposed in Japanese Patent Publication (JP-B) No. 62-50445/1987. This process, however, requires a special preparation step and in addition, the tablet thus prepared involves a problem in handling because of its insufficient strength.
In Japanese Patent Provisional Publication (JP-A) No. 5-271054/1993, proposed are an orally disintegrating tablet obtained by tableting kneaded material containing an active ingredient, a sugar and a proper amount of water under a low pressure and then drying it, and a production process thereof. This process is not suited for mass production, because the kneaded material tends to adhere to a mortar or pestle upon tableting and difficulty is encountered in water control in the production step.
In Japanese Patent Provisional Publication (JP-A) No. 8-291051/1996 or 9-48726/1997, proposed are an orally disintegrating tablet obtained by tableting a mixture of a sugar and/or sugar alcohol, a water-soluble binder, an active ingredient and the like under a low pressure, wetting the resulting tablet under moistening conditions for heightening the strength of it and then drying, and a production process thereof. This process, however, is accompanied with the problems that it requires many steps, a change in the appearance of the tablet during the moistening step impairs its commodity value and moreover, this process is not suited for an active ingredient not stable under humid conditions or an active ingredient exhibiting deliquescence.
Some processes which do not require such a special production technique but use ordinarily employed equipment have been proposed. In Japanese Patent Provisional Publication (JP-A) No. 9-71523/1997, proposed is an orally disintegrating tablet obtained by tableting, under a low pressure, a mixture comprising an active ingredient, a low-substituted hydroxypropyl cellulose as a disintegrator, crystalline cellulose as an excipient and a lubricant. This tablet, however, is inferior in practice, for example, in disintegration, solubility, texture (a feeling on the tongue) and taste owing to a large amount of a cellulose or polyvinyl pyrrolidone additive contained in it.
In Japanese Patent Provisional Publication (JP-A) No. 11-43429/1999, an orally disintegrating tablet comprising an active ingredient, a sugar and a low-substituted hydroxypropyl cellulose having a limited degree of substitution is proposed, but it has not satisfactorily improved texture or taste.
SUMMARY OF THE INVENTION
An object of the present invention is to provide a solid preparation which rapidly disintegrates in the oral cavity when taken together with the saliva in the oral cavity or a small amount of water, can be prepared easily and has strength enough to retain its form or moldability upon production or during distribution; and a production process of the solid preparation.
Finding that a solid preparation comprising a low-substituted hydroxypropyl cellulose having a loose bulk density of 0.40 g/ml or greater and a tapped bulk density of 0.60 g/ml or greater, and a sugar and/or sugar alcoho; has enough strength, is free from unpleasant taste in the oral cavity and permits rapid disintegration of the active ingredient, the present inventors have completed the present invention.
In one aspect of the present invention, there is thus provided a solid preparation comprising a low-substituted hydroxypropyl cellulose having a loose bulk density of 0.40 g/ml or greater and a tapped bulk density of 0.60 g/ml or greater and a sugar and/or sugar alcohol; and a production process of the solid preparation.
In another aspect of the present invention, there is also provided a solid preparation comprising a low-substituted hydroxypropyl cellulose having a volume average particle size, as measured by the dry laser diffraction method, of 25 &mgr;m or greater which is obtained by pulverizing a low-substituted hydroxypropyl cellulose having a loose bulk density of 0.40 g/ml or greater, a tapped bulk density of 0.60 g/ml or greater, and a volume average particle size of 30 &mgr;m or greater as measured by the dry laser diffraction method; and a sugar and/or sugar alcohol; and a production process of the solid preparation.
The solid preparation according to the present invention can easily be taken by the aged or infant having weak swallowing power, because it is excellent in formability or moldability and disintegration.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The term “loose bulk density” as used herein means the bulk density under a roughly filled state and it is determined by uniformly feeding a sample, downwards from the height of 23 cm, to a cylindrical container (material: stainless, capacity: 100 ml) of 5.03 cm in diameter and 5.03 cm in height through a 24-mesh sieve specified in Japanese Industrial Standard (JIS), leveling its upper surface and weighing one level container of the sample.
On the other hand, the term “tapped bulk density” as used herein means the bulk density under a densely filled state with the aid of tapping. The term “tapping” as used herein means an operation of dropping a container filled with a sample from a predetermined height in repetition to give a light impact on the bottom of the container, thereby filling the container with the sample densely. In practice, after the loose bulk density is determined by weighing one level container of the sample, a cap (a fixture of the below-described “Powder Tester”, product of Hosokawa Micron Corporation) is put on the container, the sample powders were added up to the upper edge of the cap and then tapping from the height of 1.8 cm is conducted 180 times. After completion of the tapping, the cap is removed, the upper surface of the container is leved, and one level container of the powders is weighed as “tapped bulk density”. The above-described operations can be conducted using “Powder Tester PT-D” (trade name; product of Hosokawa Micron Corporation).
The low-substituted hydroxypropyl cellulose to be used in the present invention has a loose bulk density of 0.40 g/ml or greater and a tapped bulk density of 0.60 g/ml or greater, preferably that available by pulverizing a low-substituted hydroxypropyl cellulose having the above-described bulk densities and in addition, having a volume average particle size, as measured by the dry laser diffraction method, of 30 &mgr;m or greater. Pulverization may be conducted in a conventional manner, for example, by using a pulverizer such as ball mill, hammer mill, knife mill or jet mill.
The term “dry laser diffraction method” as used herein means a method, like that using an HELOS apparatus of Sympatec AG/Germany, of exposing a powder sample, which has been injected by compressed air, to a laser light and determining the volume average particle size from its diffraction strength. According to, for example, page 88 of “Kaitei Zoho Funtai Bussei Zusetsu (revised and enlarged edition of Illustration of Powder Properties” edited by Funtai Kogakukai and Nippon Funtai Kogyogijutsu Kyokai, published by Nikkei Gijutsu
Obara Sakae
Tanno Fumie
Alston & Bird LLP
Shin-Etsu Chemical Co. , Ltd.
Tucker Zachary C.
LandOfFree
Solid preparation containing low-substituted hydroxypropyl... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Solid preparation containing low-substituted hydroxypropyl..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Solid preparation containing low-substituted hydroxypropyl... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3037630