Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Reexamination Certificate
1999-01-11
2001-09-11
Spear, James M. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
C424S435000, C424S441000, C424S465000, C514S770000, C514S778000, C514S781000
Reexamination Certificate
active
06287596
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a quickly disintegratable compression-molded material which has practically sufficient strength in handling of formulations in the field of pharmaceuticals and foods, and which disintegrates and dissolves quickly in the oral cavity or in water. The invention also relates to a process for producing such a material.
BACKGROUND ART
Solid peroral formulations known in the field of pharmaceuticals and foods include tablets, capsules, troches, chewable tablets, granules, and powders. However, not many formulations are designed for patient's ease in swallowing. There exists need for development of formulations which are easy to handle and easy to swallow for the aged, infants, and those having difficulty in swallowing. Tablets and capsules have drawbacks in that water is needed when they are taken. In addition, when the tablets are big or many tablets must be taken, patients have difficulty in swallowing or the tablets may become stuck within the pharynx or esophagus. These problems are very serious, especially to the aged, infants, and patients having difficulty in swallowing. Clogging of the throat sometimes suffocates such patients and medicines staying on the esophagus may cause inflammation. Troches are formulations which are gradually dissolved or disintegrated within the mouth for the application to the oral cavity or pharynx, and require no water. However, there is fear that they might stick within the pharynx or the esophagus when they are swallowed due to misuse. Chewable tablets need no water, being swallowed after chewing, but, they are not suitable for the aged or infants who have poor chewing force. Granules and powders require water for swallowing, and have drawbacks that they tend to stay in the oral cavity, choke the patient, and cause pain when they enter between false teeth.
In recent years, there is used a per tubam administration method in which medicines are given through a peroral or pernasal stomach tube catheter to a serious case having difficulty in swallowing. In practice, a prevailing method consists of injecting into the stomach tube catheter by use of a syringe a suspension prepared by adding crushed tablets or granules, or powdery medicines just as they are, to 20-30 ml of water. However, the procedures are complicated and the catheters are sometimes prone to clog since the inner diameter of the catheter is only 2-4 mm.
Against the foregoing background, there are known several formulations which are quickly disintegratable or soluble when put in the oral cavity or in water, and thus are suitable for the aged, infants, and those having difficulty in swallowing.
For example, Japanese Patent Publication (kokoku) No. 50445/1987 discloses a molded material having an open-matrix network structure obtained by filling molding pockets made of polyvinyl chloride sheet with an aqueous solution containing gelatin combined with a medicinal material, cooling and freezing the solution, and then freeze-drying the freezed solution. The publication describes that the open-matrix network structure has a density of 10-200 mg/ml, rapidly disintegrates within the oral cavity in 1-5 seconds, and is swallowed with sputum so as to prevent a patient who dislikes taking medicine from spitting it out.
In countries outside Japan, an intraoral soluble formulation known as Zydis (brand name) is commercialized by R. P. Scherer (England). The composition of the formulation is not known, but the formulation is manufactured by use of a freeze-drying process. The formulation manufactured by freeze-drying has the advantage of rapid disintegration, but it is fragile and brittle to such an extent that the hardness cannot be measured. Moreover, productivity of the formulation on an industrial scale is inferior because freeze-drying manufacturing equipment and long fabrication times are required.
International Patent Publication No. WO 93/12769 discloses an intraoral disintegratable formulation obtained by suspending a medicinal substance, lactose, and mannitol in an agar aqueous solution, solidifying the solution into a jelly state by charging the solution into molding pockets made of PTP (Press Through Package) sheet (made of polypropylene), drying the jelly under reduced pressure, and then sealing PTP-packaged products with aluminum foil. The obtained molded material has a density of 400-1000 mg/ml and is disintegrated in the oral cavity in 5-20 seconds. The publication describes that the molded material has a hardness of about 2 kg, and removal of the molded material from the PTP package does not result in cracking, crushing, or chipping. However, since the molded material has low strength as compared with conventional tablets, the material cannot be packaged in other than a PTP package, such as a bottle package. Also, productivity of the material on an industrial scale is inferior because of a long time needed for fabrication.
Several interoral disintegratable formulations which can be produced by a tableting method have been reported.
Japanese Patent Application Laid-Open (kokai) No. 271054/1993 discloses an intraoral disintegratable formulation which is obtained by tableting a mixture containing a pharmaceutically active ingredient, a carbohydrate, and a barely sufficient amount of water to moisten the surface of particles of the carbohydrate.
International Patent Publication No. WO 93/15724 discloses a rapid soluble tablet having two characteristics:
(1) the main component of the tablet is a medicinal additive having a high dissolution rate in water; and
(2) during a process where tablets containing medicinal material are produced by use of a wet granulation method, a kneaded mixture of medicinal material and medicinal additives having a high dissolution rate in water is compression molded and then dried.
Japanese Patent Application Laid-Open (kokai) No. 218028/1994 discloses:
(1) a molding method for producing tablets through a wet process, characterized by filling a mold with wet kneaded material and molding the material by use of compression molding; and
(2) a molding method for producing tablets through a wet process, in which before wet tablets are compression-molded, powder is applied on the compressed surface or the compression-punched surface of wet tablets in order to prevent wet tablets from sticking when being compressed.
Japanese Patent Application Laid-Open (kokai) No. 19589/1996 discloses a method of manufacturing tablets by charging wet powder into holes for molding tablets, and forming the powder into the tablet shape by use of a mold for molding after application of a stick-prevention film on at least one surface of the above-mentioned wet powder within the hole.
Since these methods are wet tableting methods, they use a wetting agent during molding, and molding is performed under low pressure. Therefore, they provide porous tablets having proper voids after drying and which are soft and easily disintegrated.
However, because these methods involve charging and compressing wet powder having poor fluidity, they have the disadvantage that the amount of charged material varies and sticking often occurs. Moreover, they require special drying equipment for drying soft molded material while retaining shape, and productivity on an industrial scale is inferior.
To solve this problem, an interoral disintegratable formulation produced by a dry tableting method of superior productivity has been reported.
Japanese Patent Application Laid-Open (kokai) No. 310558/1993 discloses that a highly disintegratable solid formulation composition that enables reduction of the amount of other additives having high molding characteristics; for example, cellulose-based compounds, acrylic compounds, or gelatin and the like, is obtained by mixing mannitol or lactose, which has poor bonding and molding characteristics, and sorbitol powder or granule having a bulk density of 60 g/100 ml.
International Patent Publication No. WO 95/20380 discloses an intraoral disintegratable compression molded product having rapid disintegrability and solubility in
Aritomi Hideaki
Murakami Toshio
Ueno Naoto
Daiichi Pharmaceutical Co. Ltd.
Oblon & Spivak, McClelland, Maier & Neustadt P.C.
Spear James M.
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