Hard Shell Capsule Filling Machines

Figure 6.1Basic operations common to all filling machines. (Courtesy of IMA ACTIVE division, Bologna, Italy.)





Separation


The diameter of the upper bushing or housing is larger than the diameter of the capsule body bushing; therefore, the capsule cap is retained within the upper bushing while the body is pulled into the lower bushing by vacuum. Once the capsule is opened/separated, the upper and lower housing or bushing is separated to position the capsule body for filling.



Filling


The open capsule body is then dosed with the medicament. The various types of filling mechanisms are described in detail in “Capsule Filling Machine Dosing Systems” section.



Joining and Ejection


The cap and body housings or bushings are then realigned for capsule closing. An upper plate or pin will hold the cap stationary in the housing while lower closing shaft rods will push the bodies upward into the caps until the capsules are completely joined, engaging the locking mechanism of the capsule shell. The lower closing rod or shaft will ascend, ejecting the capsule from the housing or bushing into an exit chute. Compressed air nozzles are frequently used to assist the ejection of capsules from the machine, particularly with fully automatic filling machines.




Capsule Filling Machine Dosing Systems


Capsule filling machines employ a variety of mechanisms to handle the various dosage ingredients. In every case, the dosing systems are based on volumetric fills governed by the capsule size and capacity of the capsule body. The empty capsule manufacturers provide reference tables (e.g., Table 6.13) that indicate the volume capacity of their capsule body and the maximum fill weight for each capsule size based on the density of the fill material.


Table 6.1Calculated Fill Weight Capacity


























































































Capsule Size


Body Volume (mL)


Powder Density


Capsule Capacity (mg)


0.6 g/mL


0.8 g/mL


1.0 g/mL


1.2 g/mL


000


1.37


822


1096


1370


1644


00el


1.02


612


816


1020


1224


00


0.91


546


728


910


1092


0


0.78


468


624


780


936


1el


0.54


324


432


540


648


1


0.50


300


400


500


600


2el


0.41


246


328


410


492


2


0.37


222


296


370


444


3


0.30


180


240


300


360


4


0.21


126


168


210


252


5


0.13


78


104


130


156



Source: Capsugel. Coni-Snap Hard Gelatin Capsules. 2011. Brochure: Data obtained from p. 16.



Powders


When calculating maximum fill weights for powder fills, the tapped density values for the specified powder should be used. The following dosing methods are employed.



Auger Fill Method


The auger fill method (Figure 6.24) is employed by most of the semiautomatic capsule filling machines. A rotating auger blade at the discharge of the drug hopper forces the powder through a feed shoe into the open capsule bodies housed in a rotating ring beneath the drug hopper. The filling of the capsule is primarily volumetric.5 The factors controlling the dosing volume are the rotation speed of the body ring, the rotation speed and design or pitch of the auger, and the level of powder within the drug hopper reservoir.


image fig6_2.jpg

Figure 6.2Auger fill method. (From Warner Lambert Co. Capsugel Division. Operation and Maintenance of the Type 8 Capsule Filling Machine. Capsugel Publication. Morris Plains, NJ; 1989.)



Mechanical Vibration Filling Method


The mechanical vibration method (Figure 6.36) is employed specifically by Qualicaps filling machines. A level sensor located in the powder supply chute maintains a stable powder layer that fills directly into the capsule body facilitated by a vibration plate. The accuracy of the filled powder is improved by the use of an adjustable spring plunger that removes air from the powder, creating uniform density. A scraper removes any excess fill material before capsule joining.


image fig6_3.jpg

Figure 6.3(See color insert.) Mechanical vibration filling method. (From Qualicaps. LIQFIL super 40. Brochure. Whitsett, NC; 2011.)



Dosator Method


The dosator principle (Figure 6.4) is employed by numerous fully automatic capsule filling machines. The dosator consists of a hollow metal tube with a spring-loaded adjustable piston that is volumetrically adjusted to capture the powder dose. The dosator descends into a rotating dosing bowl of powder that is being maintained at a constant level. Once the dosator reaches the bottom of the powder bed, the powder dose is pre-compressed and then the piston moves downward, compressing the powder to form a plug. The dosator moves out of the powder bed and then aligns over the open capsule body. The piston descends to the bottom of the dosing tube, discharging the dosage plug into the capsule body.7 In the case of the IMA ACTIVE dosator system, the rotary dosing bowl can be configured with a patented vacuum system for pre-compacting fine powders to create a uniform powder bed density.8


image fig6_4.jpg

Figure 6.4(See color insert.) Dosator method. (Courtesy of IMA ACTIVE division, Bologna, Italy.)



Tamping Pin/Dosing Disc Method


The tamping pin/dosing disc principle (Figure 6.59) was originally developed by Höfliger and Karg and is now utilized on numerous fully automatic, intermittent motion capsule filling machines. The method consists of a rotating steel dosing disc mounted at the base of a dosing bowl. The dosing disc has six sets of precisely bored holes. The powder is metered into the dosing bowl via an auger from a powder supply hopper to maintain a consistent powder level above the dosing disc. As the rotating dosing disc indexes the holes beneath five sets of spring-loaded tamping pins, the powder is compressed in the bores, forming a powder plug. A stationary tamping ring seated below the dosing disc retains the powder in the holes during the compaction of the powder plug. After five tamps, a deflector isolates the powder from the disc as the holes index directly over the open capsule bodies. A set of transfer pins push the powder plug out of the holes into the capsule bodies.10 Weight control on a tamping pin machine is controlled by three basic steps: (1) selecting the proper thickness of the dosing disc for the density and fill weight of the powder being run, (2) proper tamping penetration station settings, and (3) the height of the powder within the dosing bowl.


image fig6_5.jpg

Figure 6.5Tamping pin/dosing disc method. (From Harro Hofliger Packaging Systems. Modular filling and closing machine for capsules. Modu-C Mid-Speed (MS). 2010. Brochure.)



Drum Filler Method


The dose of powder is metered by dosing bores in a vacuum drum, which is rotating at the base of a powder bed (Figure 6.69). A scraper blade removes any excess powder on the drum surface as it exits the powder bed. The powder dose is retained in the dosing bores by vacuum until it is discharged into the capsule body. This method is employed by the Harro Höfliger capsule filling machines for dosing powders in the micro-dose filling range with a fill amount of 1 mg and upward.


image fig6_6.jpg

Figure 6.6(See color insert.) Drum filler method. (From Harro Hofliger Packaging Systems. Modular filling and closing machine for capsules. Modu-C Mid-Speed (MS). 2010. Brochure.)



Compression Filling Method


The compression filling method (Figure 6.711) is employed by certain models of Qualicaps filling machines. It is a modified version of the Tamping Pin/Dosing Disc method that employs four subhoppers, tapping rods, and a powder molding plate. In the first subhopper, a powder stirring agitator feeds the powder into the bores of the molding plate. In the second and third subhoppers, tapping rods compress the filling powder into the molding plate, forming a powder slug. In the fourth subhopper, a weight adjustment pusher raises the molded slug to a set height above the plate, and the excess powder is scraped away. At the fifth section, a transfer rod places the finished slug into the capsule body.12


image fig6_7.jpg

Figure 6.7Compression filling method. (From Qualicaps. LIQFIL super 40. Brochure. Whitsett, NC; 2010.)



Beads and Granules/Pellets


When calculating maximum fill weights for beads and granules fills, bulk density values should be used.



Direct Fill


The direct fill method is employed by most of the semiautomatic capsule filling machines. The beads/granules flow from a drug hopper (with the auger blade removed) through a feed shoe into the open capsule bodies housed in a rotating ring beneath the feed shoe. The factors controlling the dosing are the aperture of the feed shoe and the rotation speed of the body ring.



Vacuum Dosator Method


The vacuum dosator method (Figure 6.813) is employed by Imatic and Zanasi capsule filling machines, which are manufactured by the IMA ACTIVE division. The dosator descends partway into the pellet layer in the dosing bowl, picking up the pellets with an aspiration vacuum. Excess pellets on the dosator tip are removed by either a brush or an air-jet. The pellet product is then dosed into the capsule body by reducing the vacuum and lowering the dosator piston.13 This system is also used in the dosing of microtablets.


image fig6_8.jpg

Figure 6.8(See color insert.) Vacuum dosator method. (From IMA ACTIVE. IMATIC High Speed Capsule Filling Machine. 2011. Brochure.)



Dosing Chamber


The dosing chamber principle (Figure 6.9) is employed by numerous fully automatic capsule filling machines. It consists of various configurations of vertical or horizontal adjustable chambers that pre-measure the dose volume of beads/pellets or granules and discharge them into the capsule body.


image fig6_9.jpg

Figure 6.9Dosage chamber. (Courtesy of Robert Bosch GmbH Packaging Technology, Waiblingen, Germany.)



Dosing Disc Method


Dosing pellets using the dosing disc method was developed by Bosch Packaging Technology and is similar to the powder dosing disc method, except the tamping pins are removed, and a slide gate (Figure 6.10) is installed below the dosing disc. Pellets flow into the dosing disc holes, the slide gate opens between indexes, and the pellets drop into the open capsule bodies with the assistance of the transfer pins that purge the pellets from the disc bores.14


image fig6_10.jpg

Figure 6.10Slide gate. (Courtesy of Robert Bosch GmbH Packaging Technology, Waiblingen, Germany.)



Tablet and Capsule Overencapsulation


Overencapsulation is the most widely used method of blinding clinical supplies, performed by placing the product or products (i.e., tablets, caplets, or capsules) into an opaque capsule. This prevents the clinical investigators and subjects from differentiating between the active, placebo, or comparator drug within double-blind studies.15 Overencapsulation is also used in the manufacture of combination products.



Capsules


When overencapsulating a filled capsule, the receiving capsule shell should be two capsule sizes larger.



Tablets


There are different types of capsule filling machine dosing units used to handle single tablets, multiple tablets, or microtablets. The basic design of the tablet dosing units (Figure 6.1116) consists of a feed tube or flexible spring attached to the base of the tablet feed hopper. The tablets drop into a bushing, which transfers the tablet into the capsule body. An electromechanical device, or sensor, verifies proper dosing of the tablet within the capsule body. To assure proper handling by the dosing mechanisms, tablets should ideally be spherical or have beveled edges and coated to avoid dusting. Also, the overall tablet dimensions and hardness specifications should be kept within strict tolerances.17


image fig6_11.jpg

Figure 6.11Tablet dosing unit. (From IMA ACTIVE division. Zanasi Low-medium speed capsule filling machines. 2011. Brochure.)



Liquids/Semisolids


There has been a re-emergence of liquid-filled capsules for several reasons: They can be used for active ingredients with low melting points; they are effective for compounds that are unstable when exposed to moisture or oxygen18; they enhance the content uniformity of low dose drugs; they address safety concerns when handling highly potent APIs such as cytotoxins; they allow formulations with fewer excipients; they reduce manufacturing and plant infrastructure costs19; they overcome poor aqueous solubility; and they improve oral bioavailability.20 To note, about 60% of compounds in development exhibit poor solubility.21


When calculating maximum fill volume for liquid/semisolid fills, use a target of 85–90% of the capsule body volume.


Liquid dosing systems (Figure 6.12) employ piston pumps or a series of pumping syringes. Precise volumetric dosing is accomplished by drawing liquid from the product container and pushing it into the capsule bodies utilizing a series of slide valves. Liquid containers may be fitted with a mixer and a heating and temperature control system for thixotropic or thermosetting products.22


image fig6_12.jpg

Figure 6.12Liquid dosing system. (From IMA ACTIVE Division. ZANASI LAB. 2011. Brochure.)



Multicomponent Dosing


Many capsule filling machines can be equipped with more than one type of dosing unit to provide for filling different dosage combinations into a capsule as illustrated in Figure 6.13.23


image fig6_13.jpg

Figure 6.13Multicomponent dosing. (From Warner-Lambert Company, Capsugel Division. All About the Hard Gelatin Capsule. Capsugel Publication. Morris Plains, NJ; 1991. Report No. CAP 126E.)



Capsule Filling Machinery


The commercially available capsule filling machines are summarized in Table 6.2. Capsule filling machines can be categorized by their level of automation or their special filling capabilities described in this section.


Table 6.2Capsule Filling Machinery



















































































































































































































































































































































































































































































































































































































Manufacturer


Machine Type/Motion


Model


Maximum Hourly Output (capsules per hour)


Method of Dosing


Other Dosing Capabilities


Other


Powder


Granules


ACG-pam


ACG Worldwide


Mumbai, India


Intermittent


AFT Lab


6,000


Tamping pin


Dosing chamber


Tablets, microtablets, capsule/softgel in capsule



Intermittent


AF 25T


25,000


Tamping pin


Dosing chamber


Tablets, microtablets, capsule/softgel in capsule




Intermittent


AF 40T


40,000


Tamping pin


Dosing chamber


Tablets, microtablets, capsule/softgel in capsule




Intermittent


AF 40D


40,000


Dosator


Dosing chamber


Tablets, microtablets, capsule/softgel in capsule




Intermittent


AF 90T


90,000


Tamping pin


Dosing chamber


Tablets, microtablets, capsule/softgel in capsule




Intermittent


AF 150T


150,000


Tamping pin


Dosing chamber


Tablets, microtablets, capsule/softgel in capsule




Intermittent


AF 200T


200,000


Tamping pin


Dosing chamber


Tablets, microtablets, capsule/softgel in capsule


ZRM technology


Bosch Packaging Technology


Waiblingen, Germany


Automatic/


Intermittent


GKF 700


42,000


Tamping pin




Designed for nutraceuticals


Automatic/


Intermittent


GKF 702


42,000


Tamping pin, dosator


Dosing chamber/dosing disk/dosator


R&D mini-bowl, tablets, liquids, micro-dosing, combinations


Mini-bowl, lab kit



Automatic/


Intermittent


GKF 1400


84,000


72,000—liquids


Tamping pin


Dosing chamber/dosing disk


Tablets, liquids, combinations


GKF 1400L liquid



Automatic/


Intermittent


GKF HiProTect 1700


100,000


72,000—tablets


Tamping pin


Dosing disk or dosing chamber


Tablets, liquids, combinations


Containment for processing potent substances



Automatic/


Intermittent


GKF Capsylon 705


1505


3005


42,000


92,000


175,000


Tamping pin


Dosing disk


Powder or pellets


Designed for nutraceuticals



Automatic/


Intermittent


GKF 2000


150,000


Tamping pin


Dosing chamber


Powders/pellets




Automatic/


Intermittent


GKF 2500


150,000


Tamping pin


Dosing chamber/dosing disk


Tablets, combinations, liquids, micro-dosing




Automatic/


Intermittent


GKF 2500ASB


150,000


Tamping pin


Dosing chamber/dosing disk


Tablets, combinations, liquids, micro-dosing


Automatic troubleshooting



Automatic/


Intermittent


GKF 2500 ABS IPK


150,000


Tamping pin


Dosing chamber/dosing disk


Tablets, combinations, liquids, micro-dosing


In-process statistical weight control



Automatic/


Intermittent


GKF 2500 ASB 100%


150,000


Tamping pin


Dosing chamber/dosing disk


Tablets, combinations, liquids, micro-dosing


Integrated checkweigher



Automatic/


Intermittent


GKF 3000


175,000


Tamping pin


Dosing disk




Capsugel


Greenwood, South Carolina


USA


Semiautomatic


Cap8


Up to 29,000


Dependent on capsule size


Auger


Direct fill


Feed shoe


Tablets, capsules (using TFR 8)



Semiautomatic


Ultra 8 II


Up to 33,000


Dependent on capsule size


Auger


Direct fill


Feed shoe


Tablets, capsules (using TFR 8)




Semiautomatic


Xcelodose 120


200


“Pepper-pot”


n/a


Other small dose containers


Precise dosing of drug substance weights from 100 μg to 100+ mg



Automatic


Xcelodose 600


600+


“Pepper-pot”


n/a


Capsules only


Precise dosing of drug substance weights from 100 μg to 100+ mg



Automatic


CFS1200


1,200


n/a


n/a


Liquids


Benchtop unit


Filler and sealer



Automatic


CFS 1500C


1,500


n/a


n/a


Liquids


Floor standing machine designed for containment


Filler and sealer



Manual


ProFiller 100


2,000–3,000


Manual


Manual





Manual


ProFill DB


Overencapsulation


1,000–1,500


Manual


Manual


Overencapsulation of tablets, caplets, capsules


Designed specifically for filling DB caps capsules for double-blind studies



Semiautomatic


Xcelolab


200


“Pepper-pot”


n/a


Small dose containers




Manual


ProFiller 3000


4,500–9,000


Manual


Manual




Harro Höfliger


Packaging Systems


Doylestown, Pennsylvania, USA


Automatic/Intermittent


Modu-C LS (low speed)


24,000


Dosator


Tamping pin


Drum filler


Dosing chamber


Microtablets, tablets, capsules, liquids, combinations


Laboratory operations and production


Quick-changeable (trolleys) for powder, pellets, and tablets


Automatic/Intermittent


Modu-C MS (mid speed)


100,000


Dosator


Tamping pin


Drum filler


Dosing chamber


Microtablets, tablets, capsules, liquids, combinations


Quick-changeable (trolleys) for powder, pellets and tablets


Optional weight checking system for determination of the total and net weight



Automatic


Intermittent


Modu-C HS (high speed)


200,000


Dosator


Tamping pin


Drum filler


Dosing chamber


Microtablets, tablets, capsules, liquids, combinations


Quick-changeable (trolleys) for powder, pellets and tablets


Optional weight checking system for determination of the total and net weight



Semiautomatic


Intermittent


OmniDose


100–300


Dosator


Drum filler




Lab use


Mounted on interchangeable trolleys


IMA Active


Bologna, Italy


Intermittent


Zanasi Lab 8


Zanasi Lab 16


8,000


16,000


Dosators or tamping pin


Dosators (vacuum)


Liquids, microtablets, combinations


R&D production



Intermittent


Zanasi 6 E


Zanasi 12 E


6,000


12,000


Dosators


Dosators (vacuum)


Liquids, tablets, combinations


Statistic weight checking unit for production monitoring



Intermittent


Zanasi 25E/F


Zanasi 40/EF


25,000


40,000


Dosators


Dosators (vacuum)


Liquids, tablets, combinations


E-versions are equipped with a statistic weight checking unit for production monitoring



Intermittent


Zanasi Plus 48


Zanasi Plus 70


Zanasi Plus 85


48,000


70,000


85,000


Dosators


Dosators (vacuum)


Liquids, tablets, microtablets, combinations


Statistical weight check and adjustment


100% in-line net weight control for powders (compaction force measurement)



Intermittent


Zanasi 70C


55,000




Gelatin-coated tablet


Exclusively used for production of Press-Fit and XPress-Fit Gelcaps



Continuous


IMATIC 100


IMATIC 150


IMATIC 200


100,000


150,000


200,000


Dosators


Dosators (vacuum)



The machine can be fitted with a wide range of devices, allowing operator unattended production



Intermittent


ADAPTA 100


ADAPTA 200


100,000


200,000


Dosators


Dosators (vacuum)


Liquids, tablets, microtablets, capsules, combinations (up to 3–5 products)


Interchangeable dosing units make for flexible configuration


Total in-process control: 100% control of gross and/or net weight


MG2


Bologna, Italy


Continuous motion—intermittent (depending on the type of dosing unit installed)


“Labby”


3,000


Dosators (standard and low dosage) or dosing disk


Dosing chamber


Liquids, tablets, microtablets, capsules, caplets, micro-dosing


R&D capsule filler (single dosing station)



Continuous motion—intermittent (depending on the type of dosing unit installed)


“FlexaLab”


3,000


Dosators (standard and low dosage) or dosing disk


Dosing chamber


Liquids, tablets, microtablets, capsules, caplets, micro-dosing, combinations


R&D capsule filler


Up to two dosing units can be fitted on machine


Potent compound


Containment option



Continuous motion


Planeta


6,000–50,000


Dosators (standard and low dosage)


Dosing chamber (up to 4 types)


Liquids, tablets, microtablets, capsules, caplets, micro-dosing, combinations


Up to two dosing units can be fitted on machine


Can be fitted with “MG2 Nett Weight” control systems


Lights-out version available



Continuous motion


Planeta 100


100,000


Dosators (standard and low dosage)


Dosing chamber (up to 4 types)


Liquids, tablets, microtablets, capsules, caplets, micro-dosing, combinations


Up to two dosing units can be fitted on machine


Can be fitted with “MG2 Nett Weight” control systems


Lights-out version available


MG2


Bologna, Italy


Continuous motion


Planeta 100


Pre-weight


100,000


Dosators (low dosage)


Dosing chamber (up to 4 types)


Liquids, tablets, microtablets, capsules, caplets, micro-dosing, combinations


Can be fitted with “MG2 Multi-Nett Weight” control systems



Intermittent motion


Alterna70


70,000


Tamping pin


Dosing chamber


Tablets


Up to three dosing stations



Intermittent motion


Alternova


105,000–180,000


Tamping pin


Dosing chamber


Tablets


Up to three dosing stations



Continuous motion


G-70


G-140


70,000


140,000


Dosators (standard and low dosage)


Dosing chamber


Tablets, microtablets, combinations


Can be fitted with MG2 “Nett Weight” control systems


Lights-out version available



Continuous motion


G-250


200,000


Dosators (standard and low dosage)


Dosing chamber (up to 2 types)


Tablets (2 types), microtablets, combinations


Can be fitted with MG2 “Nett Weight” control systems


Lights-out version available



Continuous motion


MultiFlexa


250,000


Dosators (standard and low dosage)


Dosing chamber (up to 2 types)



Containment for processing potent substances WIP/CIP


Can be fitted with MG2 “Multi-Nett Weight” control systems


Lights-out version available


Qualicaps


Whitsett, North Carolina, USA


Automatic/


Intermittent


FS3


3,000




Liquids


Liquid filler and sealer


Automatic/


Intermittent


LIQFIL Super LABO


1,000–2,600


Dosing disk


Dosing chamber


Liquids, tablets


Lab unit for drug formulation



Automatic/


Intermittent


F-5


5,000


Compression/tamping


Dosing chamber


Liquids, tablets, microtablets, capsules, combinations




Automatic/


Intermittent


F-40


40,000


Compression/tamping


Dosing disk


Vibration


Dosing chamber


Liquids, tablets, microtablets, capsules, combinations




Automatic/


Intermittent


JCF-40


40,000


Auger


Auger





Automatic/


Intermittent


F-80


80,000


Compression/tamping


Dosing disk


Dosing chamber


Liquids, tablets, microtablets, capsules, combinations




Automatic/


Intermittent


F-100


100,000


Vibration


Vibration





Automatic/


Intermittent


F-120


120,000


Compression/tamping


Dosing disk


Dosing chamber


Liquids, tablets, microtablets, capsules, combinations




Automatic/


Intermittent


F-150


150,000


Compression/tamping


Dosing chamber


Liquids, tablets, microtablets, capsules, combinations



Romaco S.r.l.


Bologna, Italy


Automatic/


Intermittent


Macofar CD25


25,000


Vacuum dosators


Dosing chamber


Tablets


Double station of capsule opening


Optional statistical weight control (SWC)


Automatic/


Intermittent


Macofar CD40


40,000


Vacuum dosators


Dosing chamber


Tablets


Automatic/


Intermittent


Macofar CD60


60,000


Vacuum dosators


Dosing chamber


Tablets


Double station of capsule opening


Automatic adjustment of powder/pellet dosing with feedback from SWCl


Schaefer Technologies


Indianapolis, Indiana, USA


Semiautomatic


Model 8 S


15,000


Auger


Direct fill


Feed shoe


Tablets, capsules (using insertion ring)



Semiautomatic


STI Model 10


25,000


Auger


Direct fill


Feed shoe


Tablets, capsules (using insertion ring)



Semiautomatic


STI LF10


10,000–25,000


Dependent on capsule size/formulation


n/a


n/a


Designed for liquid filling


8 L heated hopper


Will fill products with viscosities 100–1000 cps


Automatic


Dott.Bonapace IN-CAP


3,000


Tamping pin


Dosator


Dosing chamber


Tablets, liquids



Automatic


Dott.Bonapace IN-CAP HS


7,000


Tamping pin


Dosing chamber



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Dec 8, 2017 | Posted by in PHARMACY | Comments Off on Hard Shell Capsule Filling Machines
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