GB2049469A

GB2049469A - Process for making an osmotically driven active agent dispenser

Info

Publication number: GB2049469A
Application number: GB7916315A
Authority: GB
Original assignee: Alza Corp
Current assignee: Alza Corp
Priority date: 1979-05-10
Filing date: 1979-05-10
Publication date: 1980-12-31
Also published as: IT1120987B; FR2460680A1; GB2049469B; CH637292A5; FR2460680B1; IT7968195A0; DE2919406A1; JPS55154913A; DE2919406C2

Abstract

A process for forming the outlet passageway of osmotically driven dispensers is described. These dispensers comprise an inner core of an osmotically effective drug composition, an outer shape-retaining semipermeable membrane that encapsulates the core, and an outlet passageway extending through the membrane. They are made by compressing the composition into a solid mass 13, forming a recess 15 in the mass and spray coating the mass with a semipermeable membrane. The outlet passageway is formed automatically during the spray coating step at the site of the recess. <IMAGE>

Description

SPECIFICATION Process for making an osmotically driven active agent dispenser This invention relates to a process for forming the outlet passageway in the wall of the osmotically driven dispenser of commonly owned British Patent No. 1,415,210. Briefly, those dispensers consist of an inner core of an osmotically effective active agent composition and an outer shape-retaining semipermeable wall that encapsulates the inner core. The wall has a small hole in it that serves as an outlet passageway through which the active agent composition, in solution, is dispensed. These dispensers are made by forming the core, such as by compression, coating the core with a semipermeable polymer to form the wall, and then forming the hole in the wall. Various techniques have been used to form the hole in the dispenser wall, including penetrating the wall with a drill or a laser beam.

The invention is a process for making an osmotically driven active agent dispenser comprising: forming an osmotically effective active agent composition into a solid mass; spray coating the mass with a semipermeable material to form a wall that encapsulates the mass; and forming an outlet passageway in the wall, characterized in that the outlet passageway is formed automatically in the spray coating as a result of having formed a recess or an indentation in the mass before the mass is sprayed coated, the recess or indentation being of sufficient width and depth to remain at least partly uncovered and at least partly uncoated by the semipermeable material.

This invention may be more fully understood by reference to the drawings and the following disclosure. The drawings illustrate the steps in the invention process, a dispenser that is made by the process, and the performance of a dispenser made by the invention process as compared to a similar dispenser made by a prior art process.In the drawings: Figure 1 is a partly sectional view of a tabletshaped dispenser core being formed with a mold and die; Figure 2 is a partly sectional view of an indentation being formed in the dispenser core; Figure 3 is an enlarged, partly schematic elevational view of the dispenser core formed as in Figure 1 being coated; Figure 4 is an enlarged, elevational view of the coated finished dispenser made as shown in Figures 1-3; Figure 5 is a partly sectional view of a dispenser core being formed with another mold and die; Figure 6 is an enlarged partly schematic elevational view of the dispenser core formed as in Figure 5 being coated; Figure 7 is an enlarged elevational view of the finished dispenser made as shown in Figure 5 and Figure 6; Figure 8 is a bar graph of the release rate of theophylline versus time from a prior art dispenser; and Figure 9 is a bar graph of the release rate of theophylline versus time from the dispenser of the example, infra.

Figures 1 through 3 illustrate the process of the invention being carried out in three steps to make a tablet-shaped dispenser such as might be used to administer a pharmaceutical orally. In the first step, depicted in Figure 1,an osmotically effective active agent composition 10 is charged into the cavity of a mold 11 and is compressed into a solid mass 13 (Figure 2) by a die 12. After mass 13 is formed, die 12 is removed from the mold cavity. In the second step, shown in Figure 2, a second die 14 is inserted into the cavity of mold 11 and pressed against the top of mass 13 to form a conical indentation 15 therein.

After indentation 15 has been formed, die 14 is withdrawn and mass 13 is removed from the cavity of mold 11. The third step of the process, illustrated in Figure 3, involves coating indented mass 13 with a semipermeable polymer 16. The coating technique employed is a conventional air suspension coating process in which polymer 16 is entrained in an air stream and mass 13 is placed in the path of the air stream. The entrained polymer 16 is depicted by the curved, dashed lines in Figure 3. The entrained polymer uniformly coats onto the surface of mass 13, except at the site of indentation 15, to form a thin wall 19 about mass 13. The dimensions of indentation 15 are such that entrained polymer 16 penetrates into indentation 15 only partially.Thus the coating of polymer 16 that is applied does not reach the bottom of indentation 15 nor is the mouth of indentation 15 coated over. As a result, a hole 18 is formed automatically in wall 19 at the site of indentation 15 during the coating step of the process. The finished dispenser, designated 17 in Figure 4, consists of (a) the compressed mass 13 of osmotically effective active agent composition 10 encapsulated by (b) wall 19 of semipermeable polymer 16 with (c) hole 18 extending through wall 19 to mass 13 at the site of indentation 15.

Figures 5 through 6 show an alternate way to carry out the process. The process as carried out per Figures 5 and 6 involves only two steps. In the first step, illustrated in Figure 5, the osmotically effective active agent composition 10 is charged to the cavity of a mold 20 and is compressed by a die 21 that is rammed into the mold cavity. The shape of the end of the die 21 is such that it simultaneously compresses composition 10 into a discoid-shaped solid mass 22 and forms a cylindrical indentation 23 in mass 22.

After indented mass 22 is formed die 21 is withdrawn and mass 22 is removed from the mold cavity.

In the second step, shown in Figure 6, mass 22 is coated with semipermeable polymer 16 by the same technique as shown in Figure 3 and described above.

The finished dispenser resulting from the process shown in Figures 5 and 6 is depicted in Figure 7 and is designated by the reference numeral 24. Dispenser 24 consists of an inner core (mass 22) of osmotically effective active agent composition 10 surrounded by an outer wall 25 polymer 16. Wall 25 has a hole 26 in it at the site of indentation 23. Hole 26 was formed in the same manner as hole 18 of dispenser 17.

The dimensions of the indentation that is formed in the dispenser core before it is coated are an important factor. The transverse dimension (width) of the indentation will typically be greater than twice the thickness of the coating that is applied to the core. More usually it will be at least about 5 times the thickness of the coating that is applied to the core.

The thickness of the coating will usually be in the range of about 100 to 300 microns. For indentations whose transverse dimension varies, such as a conical indentation, the transverse dimension at the mouth of the indentation may be used in determining the above relationship to the coating thickness.

The aspect ratio (depth to width) of the indentation will typically be at least about 1:5:1 and more usually at least about 2:1. Again, for indentations whose transverse dimension varies, the transverse dimension at the mouth of the indentation may be used to determine the aspect ratio. The shape of the indentation is not believed to be an important factor.

For convenience it will normally have a regular shape such as cylindrical, conical, frustoconical, hemispherical, or cubical. The indentation or recess may be formed by known techniques such as impressing, drilling, laser penetration, and the like.

The composition of the osmotically effective active agent composition used to form the dispenser core and the composition of the semipermeable material used to form the wall about the core are not features of this invention. Suitable active agent compositions and semipermeable material are disclosed in said commonly owned British Patent No. 1,415,210 filed on 4 June 1973. Likewise, the size of the outlet passageway (hole) in the coating of the dispensers made in accordance with the invention should conform to the outlet passageway dimensions disclosed in said commonly owned British Patent No.

1,415,210.

The following example further illustrates the process of the invention and the osmotically driven dispensers made thereby. This example is not intended to limit the invention in any manner.

Osmotically driven dispensers for administering theophylline orally were made as follows. Spherical molds having a diameter of approximately 0.8 cm are filled with a blend of 125 mg of theophylline monoethanolamine, a trace of the cohesive binder sodium alginate, and a trace of magnesium stearate lubricant, and the blend is compressed into spherical cores. A cylindrical recess about 625 mm in diameter and about 1250 mm deep is drilled into the surface of each core. Next, the cores are coated in a fluidized bed with cellulose acetate, 6% in methylene chloride: methanol solution, 80:20 weight:weight percent. The cellulose acetate has an acetyl content of 32%. The resulting coating is about 170 microns thick. The coating has a hole about 375 microns wide through it at the site of the recess.

Cores were made, drilled, and coated as above but with recesses about 940 microns in diameter and about 1775 microns deep. After coating, the coating had a hole about 650 microns wide in it at the site of the recess. Also, cores were made, drilled, and coated as above but with recesses about 1320 microns in diameter and about 2540 microns deep.

After coating, the coating had a hole about 1060 microns wide in it at the site of the recess.

The in vitro release rate of theophylline, expressed as the free base, from the above described dispenser having a 650 micron wide hole in the coating was determined. The release rate is depicted graphically in Figure 9. For comparison the in vitro release rate from a dispenser of essentially identical structure and composition but made by the process described in said commonly owned British Patent No. 1,415, 210 was determined. The core of the comparison dispenser was not drilled and the outlet passageway (hole) in its coating was made by mechanical drilling after the coating was applied to the core. The release rate from the comparison dispenser is depicted graphically in Figure 8.

Claims

1. A process for making an osmotically driven active agent dispenser comprising forming an osmotically effective active agent composition into a solid mass, spray coating the mass with a semipermeable material to form a wall that encapsulates the mass, and forming an outlet passageway in the wall characterized in that the outlet passageway is formed automatically in the spray coating step as a result of having formed a recess in the mass before the mass is spray coated, the recess being of sufficient width and depth to remain at least partly uncovered and at least partly uncoated by the semipermeable material.

2. The process of claim 1 further characterized in that the recess is impressed into the mass simultaneously with the formation of the mass.

3. The process of either of claims 1 or 2 further characterized in that the width of the recess is greater than twice the thickness of the wall and the aspect ratio of the recess is at least 1.5:1.

4. The process of either of claims 1 or 2 further characterized in that the width of the recess is at least 5 times the thickness of the wall and the aspect ratio of the recess is at least 2:1.

5. The process of claim 1 and as substantially described herein.