In the past, orally disintegrating tablets have been developed as highly convenient forms which can safely be taken by patients who have difficulty in swallowing drugs, elderly people, children, etc., and which can easily be taken without water. In addition to the need by said people, the need for the orally disintegrating tablets has been increased in the field of health food products, for example, in the situation where the convenience of taking without water can be utilized such as a supplement tablet for athletes during exercise. It is important, that the orally disintegrating tablets have sufficient breaking strength (tablet hardness) such that any cracks, powdering, etc. are not caused in the tablets during production or transportation of the tablets or during breaking their seals in the same manner as general tablets, and also, it is important that the orally disintegrating tablets have excellent disintegrability (disintegration time) such that the tablets immediately disintegrate in the oral cavity.
An excellent moldability will be required in the production of a tablet. The moldability means the relation between a tablet compression force and the tablet hardness obtained thereby. A process that needs a high tablet compression force could cause problems such as limitation in the performance of a tablet-compressing machine, reduction of productivity and reduction in the properties of coating particles comprised in the tablet. It will be therefore important for the particle or particulate composition constituting the tablet to have such an excellent moldability that a higher tablet hardness can be obtained with the same tablet compression force, or that the same tablet hardness can be obtained by a lower tablet compression force.
The tablet hardness and disintegrability are mutually opposing properties. In general, when a molding pressure is increased to increase the hardness, the disintegration time will tend to be prolonged, and, when the molding pressure is reduced to shorten the disintegration time, the hardness will tend to be smaller. Therefore, various technologies have been developed in order to cope with both the two properties or to achieve an optimal balance between the two properties.
Furthermore, the components of particles, granulation methods, etc. have been studied in order to impart superior moldability to the particles or particulate compositions constituting tablets.
For example, Patent Literature (PTL) 1 discloses a disintegrative particulate composition that is produced by homogeneously dispersing mannitol, xylitol, inorganic excipient, disintegrator and carmellose in the presence of water, followed by drying. The composition is characterized in that xylitol is solid-dispersed in mannitol particles to form composite particles, and that inorganic excipient, disintegrator and carmellose are dispersed in the composite particles. Said disintegrative particulate composition is produced by spray-granulation of the dispersion wherein the above components are dispersed in aqueous solvent or by spraying to carriers made of mannitol and the like.
PTL 2 discloses an orally disintegrating tablet comprising carboxymethylcellulose in an amount of 10% (w/w) or more based on the total amount including medicinal ingredients. It is produced by mixing each component, followed by formulation with a tableting machine.
PTL 3 discloses a method for the production of an orally disintegrating tablet comprising loratadine as a medicinal ingredient. The method include two granulation steps, wherein loratadine is granulated with at least one of additives such as a binder, excipient, disintegrator and the like in a first granulation step, and the resulting granules obtained in the first granulation step is further granulated with at least one of the same additives as in the first step. Carmellose is listed as an example of the disintegrator.
Furthermore, PTL 4 discloses a method for the production of an orally disintegrating tablet. The method comprises a step of spraying an aqueous suspension of a water-soluble and hydrophilic disintegrator onto a mixture of a medicinal ingredient and an excipient to give a granulate (A) comprising the medicinal ingredient, and a step of spraying an aqueous suspension of the same water-soluble and hydrophilic disintegrator as above onto the excipient to give a granulate (B) without the medicinal ingredient, and a step of compression molding of the granulates (A) and (B).
USPTO Backgrounds
USPTO Backgrounds