Material handling system
In the laboratory, materials are simply scooped or poured by hand, but in intermediate- or large-scale operations, handling of this materials often become necessary. If a system is used to transfer materials for more than one product steps must be taken to prevent cross contamination. Any material handling system must deliver the accurate amount of the ingredient to the destination. The type of system selected also depends on the characteristics of the materials. More sophisticated methods of handling materials such as vacuum loading systems, metering pumps, screw feed system.
Vacuum loading machine
Powders to be used for encapsulation or to be granulated must be well blended to ensure good drug distribution. Inadequate blending at this stage could result in discrete portion of the batch being either high or low in potency. Steps should also be taken to ensure that all the ingredients are free of lumps and agglomerates. For these reasons, screening and/or milling of the ingredients usually makes the process more reliable and reproducible.
The equipment used for blending are: V.
. Blender loading. SCALE UP CONSIDERATIONS Time of blending .blender Double cone blender Ribbon blender Slant cone blender Bin blender Orbiting screw blenders vertical and horizontal high intensity mixers. Size of blender.
V – cone blender
Double cone blender
To change the particle size distribution.Granulation
The most common reasons given to justify granulating are: 1. wet granulation has been carried out using.
. Uniform dispersion of active ingredient. 3. To impart good flow properties to the material. Sigma blade mixer. Traditionally. To increase the apparent density of the powders. Heavy-duty planetary mixer. 2. 4.
Sigma blade mixer
.Wet granulation can also be prepared using tumble blenders equipped with highspeed chopper blades.
Drying times at specified temperatures and airflow rates must be established for each product.
The most common conventional method of drying a granulation continues to be the circulating hot air oven. and if soluble dyes are involved. and the depth of the granulation on the trays. the drying process will be inefficient. migration of the dye to the surface of the granules. If the granulation bed is too deep or too dense. air temperature. and for each particular oven load. The important factor to consider as part of scale-up of an oven drying operation are airflow. which is heated by either steam or electricity.
The important factor considered as part of scale up fluidized bed dryer are optimum loads.
. rate of airflow. inlet air temperature and humidity.Fluidized bed dryers are an attractive alternative to the circulating hot air ovens.
The conventional sugar coating pan has given way to perforated pans or fluidized-bed coating columns.
Sugar coating is carried out in conventional coating pans. has undergone many changes because of new developments in coating technology and changes in safety and environmental regulations. The development of new polymeric materials has resulted in a change from aqueous sugar coating and more recently. to aqueous film coating. The tablets must be sufficiently hard to withstand the tumbling to which they are subjected in either the coating pan or the coating column.
This is because of increased pressure & abrasion to which tablets are subjected when batch size is large & different in temperature and humidity to which tablets are exposed while coating and drying process.
. A film coating solution may have been found to work well with a particular tablet in small lab coating pan but may be totally unacceptable on a production scale.Some tablet core materials are naturally hydrophobic. film coating with an aqueous system may require special formulation of the tablet core and/or the coating solution. and in these cases.
DRY BLENDING WET GRANULATION WEIGHING SIZING GRANULATION DRYING BLENDING LUBRICATION COMPRESSION DRY GRANULATION WEIGHING SIZING BLENDING COMPACTION MILLING LUBRICATION COMPRESSION
WEIGHING SIZING BLENDING LUBRICATION COMPRESSION COATING
Capsules are solid dosage forms in which the drug substance is enclosed in either a hard or soft soluble container or shell of a suitable form of gelatin. Packing and labeling
. Uniformity testing 6. Granulation and lubrication 3. Filling of capsules 5. Mixing of ingredient 2. Steps in capsule production 1. Making of capsules 4.
. Both tablets & capsules are produced from ingredients that may be either dry blended or wet granulated to produce a dry powder or granule mix with uniformly dispersed active ingredients. To produce capsules on high speed equipment .The manufacturing process for capsulated products often same to that tablets. bulk density & compressibility required to promote good flow properties & result in the formation of compact of the right size and sufficient cohesiveness to be filled in to capsule shells.the powder blend must have the uniform particle size distribution.
0 – 9. depending upon the source of the collagen and extraction.0 for type A and 4.8 – 5. Shell composition : Gelatin : Prepared by the hydrolysis of collagen.0 for type B) and by their viscosity and film forming characteristics. The two types can be differentiated by their isoelectric points (7. Gelatin in its chemical and physical properties. There are two basic types of gelatin: Type – A and Type – B.
.Manufacture of Hard Gelatin Capsules
but also may play a role in improving patient compliance. E. white.g. stimulants and antidepressants. hallucinogenic effects. Colorants : Various soluble synthetic dyes (“coal tar dyes”) and insoluble pigments are used. orange or yellow.
. The physicochemical properties of gelatin of most interest to shell manufactures are the bloom strength and viscosity.. lavender. Combination of pork skin and bone gelatin are often used to optimize shell characteristics. Not only play a role in identifying the product. analgesia.
Opaque capsules may be employed to provide protection against light or to conceal the contents.
. parabens are often selected. Preservatives : When preservatives are employed.Opaquing agents : Titanium dioxide may be included to render the shell opaque.
2) Shell manufacture :
jacketed dipping pan. pins are elevated and rotated 2-1/2 times until they are facing upward. whereas the dipping solution is maintained at a temperature of about 500C in a heated. This rotation helps to distribute the gelatin over the pins uniformly and to avoid the formation of a bead at the capsule ends. The pins are at ambient temperature.
Dipping : Pairs of the stainless steel pins are dipped into the dipping solution to simultaneously form the caps and bodies.I. II. Rotation : After dipping.
. The length of time to cast the film has been reported to be about 12 sec.
Under drying will leave the films too sticky for subsequent operation.III. Drying : The racks of gelatin coated pins then pass into a series of four drying oven. Stripping : A series of bronze jaws strip the cap and body portions of the capsules from the pins.
. A temperature elevation of only a less degrees is permissible to prevent film melting. IV. Drying is mainly done by dehumidification.
knives are brought against the shells to trim them to the required length. As the collects rotate.
. Joining : The cap and body portions are aligned concentrically in channels and the two portions are slowly pushed together. Trimming :
The stripped cap and body portions are delivered to collects in which they are firmly held. VI.V.
.3) Sorting : The moisture content of the capsules as they are from the machine will be in the range of 15 – 18% w/w. capsules are printed before filling. 4) Printing : In general. Defects are generally classified according to their nature and potential to cause problems in use. During sorting. Generally. the capsules passing on a lighted moving conveyor are examined visually by inspectors. printing is done on offset rotary presses having throughput capabilities as high as three-quarter million capsules per hour.
5) Sizes and shapes : For human use.240 0. empty gelatin capsules are manufactured in eight sizes.296 0.544 0.15 Fill weight(g) at 0.37 0.104
.95 0.21 0. Capsule capacities in table:
Size 000 00 0 1 2 3 4 5 Volume 1.37 0.8 g/cm3 powder density 1.400 0.096 0.30 0.68 0.168 0.760 0. ranging from 000 to 5.50 0.
. 15. and 12 having capacities of about 30.g. e. Some manufactures have employed distinctive shapes. symmetrical bullet shape. respectively. Lilly’s pulvule tapers to a bluntly pointed end. Three larger size are available for veterinary use: 10. and 7.5 g. Smith Kline Beacham’s spansule capsules taper at both the cap and body ends. 11. The standard shape of capsules is traditional. The largest size normally acceptable to patient is a No: 0.
6) Sealing : Capsules are sealed and somewhat reshaped in the Etaseal process. This thermal welding process forms an indented ring around the waist of the capsule where the cap overlaps the body. To maintain a relative humidity of 40-60% when handling and storing capsules.
. 7) Storage : Finished capsules normally contain an equilibrium moisture content of 13-16%.
.Filling of hard gelatin capsules
Equipment used in capsule filling operations involves one often of two types of filling systems. Hofliger-Karg machine: Formation of compacts in a die plate using tamping pins to form a compact. Zanasi or Martelli encapsulator: Forms slugs in a dosatar which is a hollow tube with a plunger to eject capsule plug.
ZANASI AUTOMATIC CAPSULE FILLING MACHINE
HOFLIGER KARG AUTOMATIC CAPSULE FILLING MACHINE
the scale-up process involve bulk density.In this both system.
. and lubricant distribution. compressibility. powder flow. Overly lubricated granules are responsible for delaying capsule disintegration and dissolution.
OSAKA MODEL R-180 SEMI AUTOMATIC CAPSULE FILLING MACHINE
Up to 5% sugar may be included to give a “chewable” quality to the shell.3-1.0-1. however. the basic component of soft gelatin shell is gelatin.0 for very hard shell to 1. the shell has been plasticized. The residual shell moisture content of finished capsules will be in the range of 6-10%.Manufacture of Soft Gelatin Capsules
I.8 for very soft shell. The ratio of dry plasticizer to dry gelatin determines the “hardness” of the shell and can vary from 0. Composition of the shell: Similar to hard gelatin shells.
The pH of the lipid can be between 2.5. Emulsion can not be filled because water will be released that will affect the shell. The liquids are limited to those that do not have an adverse effect on gelatin walls. Formulation : Formulation for soft gelatin capsules involves liquid.II. rather than powder technology. Materials are generally formulated to produce the smallest possible capsule consistent with maximum stability. therapeutic effectiveness and manufacture efficiency.5 and 7.
Water immiscible. mineral oils.The types of vehicles used in soft gelatin capsules fall in to two main groups:
1. The sealing temperature of gelatin films is 37-400C. Water miscible. volatile or more likely more volatile liquids such as vegetable oils. medium-chain triglycerides and acetylated glycerides.
All liquids used for filling must flow by gravity at a temperature of 350c or less. nonvolatile liquids such as low molecular weight PEG have come in to use more recently because of their ability to mix with water readily and accelerate dissolution of dissolved or suspended drugs.
and Inserting the “ sandwich” under a die press where the capsules are formed and cut out. Application of vacuum to draw the sheet in to the die pockets.
. Filling the pockets with liquor or paste. Plate process : The process involved
Placing the upper half of a plasticized gelatin sheet over a die plate containing numerous die pockets. Manufacture process : A. Folding the lower half of gelatin sheet back over the filled pockets.III.
As the die rolls rotate. the die cavities are machined in to the outer surface of the two rollers.B. The die pockets on the left hand roller form the left side of the capsule and the die pockets on the right hand roller form the right side of the capsule. the convergence of the matching die pockets seals and cuts out the filled capsules. Two plasticized gelatin ribbons are continuously and simultaneously fed with the liquid or paste fill between the rollers of the rotary die mechanism. Rotary die press: In this process.
A die roll. Accogel process: In general. the measured doses are transferred to the gelatin-linked pockets of the die roll. this is another rotary process involving
A measuring roll.
As the measuring roll and die rolls rotate. Pressure developed between the die roll and sealing roll seals and cuts out the capsules. and A sealing roll. The continued rotation of the filled die converges with the rotating sealing roll where a second gelatin sheet is applied to form the other half of the capsule.C.
one-piece soft gelatin capsules by a “bubble method”.
. Bubble method: The Globex Mark II capsulator produces truly seamless.4.
the liquids are discharged from the concentric tube orifice into a chilled-oil column as droplets that consists of a liquid medicament core within a molten gelatin envelop.
. The droplets assume a spherical shape under surface tension forces and the gelatin congeals on cooling. By means of a pulsating pump mechanism. A concentric tube dispenser simultaneously discharges the molten gelatin from the outer annulus and the liquid content from the tube. The finished capsules must be degreased and dried.
. the fill material must be pumpable. any materials filled into hard capsules must not dissolve. Generally. together with the development of high-resting state viscosity fills. has now made liquid/semisolid-filled hard gelatin capsules. As with soft gelatin capsules. Soft/Liquid-filled hard gelatin capsules:
Important reason: the standard for liquid filled capsules was inability to prevent leakage from hard gelatin capsules.IV. As banding and of self-locking hard gelatin capsules. alter or otherwise adversely affect the integrity of the shell.
Three formulation strategies based on having a high resting viscosity after filling have been described. Thus. Mixed thermal-Thixotropic systems. Thixotropic formulations. by selecting excipients with varying HLB balance.
The more lipophilic contents. varying release rate may be achieved. 2. the slower the release rate. Thermal-setting formulations.
CAPSULE POLISHING MACHINE
AUTO MATIC CAPSULE ARRANGEMNT
The theory and practice of industrial pharmacy. Herbert A. Volume 3. 4. Page no. Leon Lachman. Pharmaceutical process scale –up edited by Michael Levin. Kanig.References
1. 4th edition. Rhodes. Edited by Gilbert S. 681703. 2. 3. Lieberman. Lieberman. Third edition.google. Leon Lachman. Joseph B. second edition. www. Modern pharmaceutics. Schwartz.com
. 303-365. 5. Herbert A. Page no. Banker & Christopher T. Joseph L. Pharmaceutical dosage forms: Tablets. Varghese publishing house.
Dept. of Pharmaceutics
. April 30.