It is known to produce solid pharmaceutical preparations which ensure a constant release of active ingredient throughout the gastrointestinal tract over a long period of time and thus ensure a constant concentration of active ingredient in the body. These delayed release forms make it possible to reduce the number of doses of the drug to be administered daily and thus simplify the treatment plan considerably. Usually, tablets and capsules which are provided with a coating which regulates the release of active ingredient are used as delayed release forms. It has also already been proposed that delayed release forms be produced from a granulate mixture the individual components of which release the active pharmaceutical ingredient at different rates.
In addition, tablets with score lines are known which enable the tablets to be divided into partial doses in order to meet special therapeutic requirements. Divisible tablets of this kind must, in particular, satisfy the requirement of being easy and safe to divide and of ensuring precise dosage, even when broken into fragments.
One disadvantage of delayed release tablets provided with coatings is that any division of the tablet critically affects the total surface area of the tablet, that is, it increases it and some of the delaying coating is lost. As a result, the characteristics of the release of active ingredient are significantly altered, so that in many cases the fragments of the divisible delayed release tablet no longer have the property of delayed and continuous release of active ingredient or retain this property only to a very restricted extent.
In order to overcome this difficulty at least partially, an oblong delayed release tablet is proposed in German Auslegeschrift No. 3,030,622. This tablet consists of an elongate pressed object which is optionally provided with a coating and is formed from at least one active substance in an excipient composition which ensures a delayed, controlled release of active substance. This pressed object has to have certain characteristics with regards to its geometric dimensions.
The delayed release tablet according to German Auslegeschrift No. 3,030,622 has the following disadvantages:
(1) Since the rate of release of the active ingredient in this tablet is dependent on the size and nature of the total surface area, and the size and nature of the surface area are affected by any division of the tablet, such division of the tablet will inevitably affect the rate of release of the active ingredient from the fragments, even though the reduction in the delaying effect should surprisingly be less than expected.
(2) The delayed release form is tied to a certain shape and, in particular, to certain conditions regarding the geometric dimensions. Round delayed release tablets with score lines cannot be produced by the measures disclosed in this prior publication.
(3) In tablet pressing technology, experience has shown that as a result of the different conditions of compression near the score line in the pressed blanks, particularly in the case of deep notches, the tablet will tend to break next to rather than at the score line. Therefore, in this embodiment of the prior art, a poor degree of accuracy in dosage can be expected from the tablet fragments.
Finally, orally administerable pharmaceutical preparations are known wherein the active substance is embedded in a polymer. Pharmaceutical preparations of this kind are normally produced by dissolving the active ingredient together with a polymer in a solvent, then evaporating the solvent and granulating the solid mixture. Normally, the removal of the solvent and the granulation are carried out in a single operation by spray-drying.
Pharmaceutical preparations of this type are intended for the purpose of distributing the active ingredient in a finely dispersed form through the polymer and increasing the surface area of the substance which is to be dissolved, so as to accelerate and not delay the dissolving process.
USPTO Backgrounds
USPTO Backgrounds