Method of producing solid dosage forms

Details Method of producing solid dosage forms Method of producing solid dosage forms

2001-05-09

2004-05-18

Theisen, Mary Lynn (Department: 1732)

Plastic and nonmetallic article shaping or treating: processes

With severing, removing material from preform mechanically,...

To form particulate product

C264S310000, C425S363000

Reexamination Certificate

active

06737005

ABSTRACT:

The present invention relates to a process for producing solid dosage forms by producing a plastic mixture which comprises at least one active ingredient and at least one polymeric binder, and shaping the plastic mixture to the solid dosage forms in a molding calender with two counterrotating forming rolls.
A process of this type is disclosed, for example, in U.S. Pat. No. 4,880,585. In this process, a composition containing active ingredient and binder is plasticized using an extruder, and the resulting melt is subjected to a shaping in a molding calender. The molding rolls of the molding calender have on their surface depressions with mutually corresponding outlines. The depressions on the surfaces of the molding rolls briefly meet at the contact line of the molding rolls to form molds for the active ingredient-containing melt and then, as rotation of the molding rolls continues, diverge again to release the molded dosage forms. This process has certain disadvantages. Thus, the depressions on the surface of the molding rolls must exactly coincide with their outlines during the shaping of the plastic mixture in order to achieve complete closure of the mold. Even tiny relative displacements of the depressions, e.g. in the region of a few micrometers, immediately lead to a detectable mismatch of the upper side and lower side of the dosage form. On the one hand this requires high precision in producing the molding rolls and, on the other, there must be exactly synchronous movement of the molding rolls in the calender toward one another. This is possible only with elaborately designed machinery. The production of the molding rolls is complicated and costly because cavities with a three-dimensional structure must be provided in the roll surfaces. This particularly applies when more complicated geometries, e.g. divisible tablets with a score are desired. Because of the need for the two molding rolls to be accurately aligned in the known molding calendering processes, no segmentation of the molding rolls into individual roll disks which each comprise only one or a few lanes of depressions, and can be combined to a multilane roll as required, is possible because the individual segments easily become twisted due to the molding pressure occurring during the calendering. However, this twisting leads to the upper and lower halves of the tablet molds not being exactly coincident on rotation. Segmentation of the molding rolls is, however, desirable in order for it to be necessary, for example if individual cavities are damaged, to replace only one roll disk and not the entire roll, or for it to be possible to combine diverse molds in one roll as desired.
It has already been proposed to combine a molding roll having depressions on its surface with a second roll which contains no depressions (smooth roll). In this case there is no need for accurate alignment of the two rolls. However, the disadvantage in this case is that elaborate production of at least one of the two rolls is still necessary. In addition, there are very limited possibilities for the shape of the tablet molds with this combination.
It is an object of the present invention to provide a simple and cost-effective process for producing solid dosage forms in which no problems relating to mismatch of upper and lower halves of the dosage forms occur.
We have found that this object is achieved when the molding rolls are designed on their surface so that they are able to intermesh.
The present invention therefore relates to a process for producing solid dosage forms by
a) producing a plastic mixture which comprises at least one active ingredient and at least one polymeric binder, and
b) shaping the plastic mixture to the solid dosage forms in a molding calender with two counterrotating molding rolls, wherein one molding roll has at least one annular groove running along its periphery and the other molding roll has at least one ring, running along its periphery, of teeth extending radially outward and able to engage in the annular groove. The teeth are shaped so that, on maximum engagement in the annular groove, they essentially completely fill the cross-section of the annular groove, i.e. the annular groove and the teeth are essentially complementary in cross-section profile.
The intermeshing of the molding rolls makes it unnecessary to align the two individual rolls accurately, because only one roll of the pair of rolls has an angle-dependent surface structure. It is therefore possible to select considerably simpler designs of machinery for the calenders accomodating the molding rolls.
Molding rolls to be used according to the invention are known as “prism rolls” from compaction technology. In this connection, reference is made to B. Pietsch, Aufbereitungs-Technik 3 (1970) pp. 128-138. The use of such rolls for compacting free-flowing materials to granules is described therein. Problems of a possible mismatch between upper and lower half of the compacts formed are not mentioned in this connection.
Pairs of rolls to be used according to the invention make it possible, despite the simple design of the rolls, for the solid dosage forms produced in this way to have a considerable variety of shapes. The possible variations relate primarily to the design of the annular groove and the design of the interstice between consecutive teeth in a ring. Thus, the annular groove may have a series of different cross-section profiles (projection onto a plane containing the axis of the roll). The annular groove may have a rectangular, triangular, rounded or any other cross-section. It is generally preferred for the annular groove to have a rounded cross-section profile for easier demolding of the shaped dosage forms.
The longitudinal profile of the interstices between consecutive teeth in a ring (i.e. the projection of the interstice onto a plane perpendicular to the axis of the roll) is likewise subject to variation. Thus, the interstices may have triangular, parallelogram-shaped, rounded or another longitudinal profile. However, it is generally preferred for the interstices between consecutive teeth in a ring to have a rounded longitudinal profile.
The resulting dosage forms may have in this way, for example, a prism shape, truncated prism shape, tetrahedral shape or saddle shape, and the saddle shape is preferred.
In a preferred embodiment of the process according to the invention, a circulating bar is present on the base of the annular groove and the teeth have a corresponding recess. It is possible in this way to produce divisible tablets having a score on one side of their surface.
It is likewise possible for a bar which does not extend up to the outer surface of the roll to be present between consecutive teeth in a ring. It is likewise possible in this way to produce divisible tablets with a score.
In order to facilitate demolding of the formed dosage forms from the annular groove and the interstices between the teeth, it is possible to keep the contact pressure between the two molding rolls low, or to provide a small spacing between the molding rolls, e.g. 0.1-1 mm. This results in a “tablet ribbon” in which the individual dosage forms are still connected together by narrow flashes. The individual dosage forms can, especially when the plastic mixture shows increased brittleness after complete cooling, easily be separated from one another. It may be appropriate then to deflash the resulting dosage forms.
After the molding process, the drug forms are allowed to cool and solidify, e.g. on a cooling belt.
The present process for producing solid dosage forms comprises the production of a plastic mixture. This usually takes place by mixing and melting at least one pharmacologically acceptable polymeric binder, at least one active pharmaceutical ingredient and, where appropriate, conventional pharmaceutical additives in the presence or absence of a solvent. These process steps can be carried out in known manner.
The components can first be mixed and then be melted and homogenized. However, it has proven to be preferred, especially on use of sensiti

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