Tablets & Capsules

Essential properties of tablets

Accurate dosage of medicament, uniform in weight, appearance and diameter Have the strength to withstand the rigors of mechanical shocks encountered in its production, packaging, shipping and dispensing Release the medicinal agents in the body in a predictable and reproducible manner Elegant product, acceptable size and shape Chemical and physical stabilities

Advantages
Production aspect
Large scale production at lowest cost Easiest and cheapest to package and ship High stability

User aspect (doctor, pharmacist, patient)

Easy to handling Lightest and most compact Greatest dose precision & least content variability Coating can mark unpleasant tastes & improve patient. acceptability

Disadvantages
Some drugs resist compression into dense compacts Drugs with poor wetting, slow dissolution, intermediate to large dosages may be difficult or impossible to formulate and manufacture as a tablet that provide adequate or full drug bioavailability Bitter taste drugs, drugs with an objectionable odour, or sensitive to oxygen or moisture may require encapsulation or entrapment prior to compression or the tablets may require coating

Absorption of drug form tablets

Ingredients used in tablet formulations

Drugs Fillers, diluent, bulking agent Binders
To bind powders together in the wet granulation process To bind granule together during compression

To make a reasonably sized tablet

Disintegrants
To promote breakup of the tablets To promote rapid release of the drug

Lubricants
To reduce the friction during tablet ejection between the walls of the tablet and the walls of the die cavity

Glidants
Reducing friction between the particles To improve the flow properties of the granulations

Antiadherants
To prevent adherence of the granules to the punch faces and dies

Dissolution (enhancers and retardants) Wetting agents Antioxidants Preservatives Coloring agents Flavoring agents

Types of tablets
Route of administration
Oral tablets Sublingual or buccal tablets Vaginal tablets

Production process
Compressed tablets Multiple compressed tablets Tablet within a tablets: core and shell Multilayer tablet

 Sugar coated tablets Protect tablets from moisture Mask odor and flavor Elegance Film coated tablets Thin film coat Soluble or insoluble polymer film

 Chewable tablets Rapid disintegrate Antacid, flatulance: rapid action Children drug Effervescent tablets Dissolve in the water before drink

Tablet production
Powders intended for compression into tablets must possess two essential properties
Powder fluidity The material can be transported through the hopper into the die To produce tablets of a consistent weight Powder flow can be improved mechanically by the use of vibrators, incorporate the glidant

 Powder compressibility

The property of forming a stable, intact compact mass when pressure is applied

Tableting procedure
Filling
Compression Ejection

SCREENING Screener is an essential part of every pharmaceutical production process, particularly as product quality & integrity are so important. The use of a sieve gets rid of oversized contamination to ensure that ingredients & finished products are quality assured during production and before use or despatch.

GRANULATION Granulation may be defined as a size enlargement process which converts small particles into physically stronger & larger agglomerates. Granulation method can be broadly classified into two types:A. WET GRANULATION Wet granulation process simply involves wet massing of the powder blend with a granulating liquid, wet

Wet granulation has been carried out using, Sigma blade mixer, Heavy-duty planetary mixer

Sigma blade mixer

Planetary mixer

B. DRY GRANULATION In dry granulation process the powder mixture is compressed without the use of heat and solvent. It is the least desirable of all methods of granulation. The two basic procedures are to form a compact of material by compression and then to mill the compact to obtain a granules.

DRYING After the process of granulation, product exists as a wet mass from which liquid must be removed, since the presence of water leads to impairment of flow properties.

The essential constituents of an effective piece of drying equipment are a heat supply to increase the temperature & thereby reduce relative humidity, a device for removal of evaporated water. The fluidized bed dryer is the most commonly used device for drying tablet granules.

Fluidized bed dryer

MILLING Milling process is not an easily contained unit operation because of the high possibility of cross contamination. Whether used to reduce size or distribute colour or active ingredients, milling process is an integral part of the successful development & mass production of formulae

Particle size reduction can be carried out by passing all the material through an oscillating granulator, a hammer mill etc

Oscillating type granulator

Hammer mill

BLENDING The successful mixing of powder is acknowledged to be more difficult unit operation because, unlike the situation with liquid, perfect homogeneity is practically required

The equipment used for blending V- blender Double cone blender Ribbon blender Slant cone blender Bin blender Orbiting screw blenders vertical and horizontal high intensity mixers

V cone blender

Double cone blender

Ribbon blender

COMPRESSION After the preparation of granules (in case of wet granulation) or sized slugs (in case of dry granulation), they are compressed to get final product. The compression is done either by single punch machine (stamping press) or by multi station machine (rotary press).

The tablet press is a high-speed mechanical device. It 'squeezes' the ingredients into the required tablet shape with extreme precision. It can make the tablet in many shapes, although they are usually round or oval. Also, it can press the name of the manufacturer or the product into the top of the tablet.

COATING Coated tablets are defined as tablets covered with one or more layers of mixture of various substances such as natural or synthetic resins, gums, inactive and insoluble filler, sugar, plasticizer, polyhydric alcohol , waxes, authorized colouring material and some times flavoring material. Coating may also contain active ingredient.

TYPE OF TABLET COATING PROCESS:A.SUGAR COATING Compressed tablets may be coated with coloured or uncoloured sugar layer. The coating is water soluble and quickly dissolves after swallowing. The sugar coat protects the enclosed drug from the environment and provides a barrier to objectionable taste or odour.

B.FILM COATING-Film coating is deposition of a thin film of polymer surrounding the tablet core. Film coating is more favoured over sugar coating. C.ENTERIC COATING-This type of coating is used to protect tablet core from disintegration in the acid environment of the stomach.

PACKAGING Pharmaceutical manufacturers have to pack their medicines before they can be sent out for distribution. The type of packaging will depend on the formulation of the medicine.

There are generally two types of packing:1.Strip sealing 2.Blister packing 'Blister packs' are a common form of packaging used for a wide variety of products. They are safe and easy to use and they allow the consumer to see the contents without opening the pack.

Many pharmaceutical companies use a standard size of blister pack. This saves the cost of different tools and to change the production machinery between products. The blister pack itself must remain absolutely flat as it travels through the packaging processes,

Tablet compression machines

Hopper for holding and feeding granulation to be compressed Dies that define the size and shape of the tablet Punches for compressing the granulation within the dies Cam tracks for guiding the movement of the punches Feeding mechanisms for moving granulation from the hopper into the dies

Single punch machine

The compression is applied by the upper punch Stamping press

Single Punch Machine (Tablets)

Upper and Lower Collar

Collar locker

Multi-station rotary presses

The head of the tablet machine that holds the upper punches, dies and lower punches in place rotates As the head rotates, the punches are guided up and down by fixed cam tracks, which control the sequence of filling, compression and ejection. The portions of the head that hold the upper and lower punches are called the upper an lower turrets

The portion holding the dies is called the die table The pull down cam (C) guides the lower punches to the bottom, allowing the dies to overfill The punches then pass over a weight-control cam (E), which reduces the fill in the dies to the desired amount

A swipe off blade (D) at the end of the feed frame removes the excess granulation and directs it around the turret and back into the front of the feed frame The lower punches travel over the lower compression roll (F) while simultaneously the upper punches ride beneath the upper compression roll (G)

The upper punches enter a fixed distance into the dies, while the lower punches are raised to squeeze and compact the granulation within the dies After the moment of compression, the upper punches are withdrawn as they follow the upper punch raising cam (H) The lower punches ride up the cam (I) which brings the tablets flush with or slightly above the surface of

The tablets strike a sweep off blade affixed to the front of the feed frame (A) and slide down a chute into a receptacle At the same time, the lower punches re-enter the pull down cam (C) and the cycle is repeated

Although tablet compressing machinery has undergone numerous mechanical modifications over the years, the compaction of materials between a pair of moving punches within a stationary die has remained unchanged The principle modification from earlier equipment has been an increase in production rate which is regulated by
Number of tooling sets Number of compression stations Rotational speed of the press

Special adaptations of tablet machines allow for the compression of layered tablets and coated tablets A device that chills the compression components to allow for the compression of low-melting point substances such as waxes i.e. suppositories

DIFFERENT PUNCHES &DIES

DOUBLE ROTARY MACHINE

UPPER PUNCH AND LOWER PUNCH

Tableting methods
Dry methods
Direct compression Dry granulation

Wet methods
Wet granulation

Direct compression
Tablets are compressed directly from powder blends of the active ingredient and suitable excipients No pretreatment of the powder blends by wet or dry granulation procedures is necessary

Advantages
Economy
Machine: fewer manufacturing steps and pieces of equipment Labor: reduce labor costs Less process vallidation Lower consumption of power

Manufacture of Hard Gelatin Capsules

Manufacture of Hard Gelatin Capsules

1. Shell composition : Gelatin : Prepared by the hydrolysis of collagen. Gelatin in its chemical and physical properties, depending upon the source of the collagen and extraction.
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 There are two basic types of gelatin: Type A and Type B. The two types can be differentiated by their isoelectric points (7.0 9.0 for type A and 4.8 5.0 for type B) and by their viscosity and film forming characteristics.

Combination of pork skin and bone gelatin are often used to optimize shell characteristics. The physicochemical properties of gelatin of most interest to shell manufactures are the bloom strength and viscosity.

Colorants : Various soluble synthetic dyes (coal tar dyes) and insoluble pigments are used. Not only play a role in identifying the product, but also may play a role in improving patient compliance. E.g., white, analgesia; lavender, hallucinogenic effects; orange or yellow, stimulants and antidepressants.

Opaquing agents : Titanium dioxide may be included to render the shell opaque. Opaque capsules may be employed to provide protection against light or to conceal the contents. Preservatives : When preservatives are employed, parabens are often selected.

Shell manufacture

I.

Dipping : Pairs of the stainless steel pins are dipped into the dipping solution to simultaneously form the caps and bodies. The pins are at ambient temperature; whereas the dipping solution is maintained at a temperature of about 500C in a heated, jacketed dipping pan. The length of time to cast the film has been reported to be about 12 sec. II. Rotation : After dipping, pins are elevated and rotated 2-1/2 times until they are facing upward. This rotation helps to distribute the gelatin over the pins uniformly and to avoid the formation of a bead at the SRTM University, NandedDept. of capsule ends. 08 June 2009 66 Pharmaceutics

III. Drying : The racks of gelatin coated pins then pass into a series of four drying oven. Drying is mainly done by dehumidification. A temperature elevation of only a less degrees is permissible to prevent film melting. Under drying will leave the films too sticky for subsequent operation. IV. Stripping : A series of bronze jaws strip the cap and body portions of the
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V.

VI.

Trimming : The stripped cap and body portions are delivered to collects in which they are firmly held. As the collects rotate, knives are brought against the shells to trim them to the required length. Joining : The cap and body portions are aligned concentrically in channels and the two portions are slowly pushed together.
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3) Sorting : The moisture content of the capsules as they are from the machine will be in the range of 15 18% w/w. During sorting, the capsules passing on a lighted moving conveyor are examined visually by inspectors. Defects are generally classified according to their nature and potential to cause problems in use. 4) Printing : In general, capsules are printed before filling. Generally, printing is done on offset rotary presses having throughput capabilities as high as 3-quarter million capsules/hr
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5) Sizes and shapes : For human use, empty gelatin capsules are manufactured in eight sizes, ranging from 000 to 5. Capsule capacities in table:
Size 000 00 0 Volume 1.37 0.95 0.68 Fill weight(g) at 0.8 g/cm3 powder density 1.096 0.760 0.544

1
2 3 4
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0.50
0.37 0.30 0.21
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0.400
0.296 0.240 0.168 0.104
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0.15

The largest size normally acceptable to patient is a No: 0. Three larger size are available for veterinary use: 10, 11, and 12 having capacities of about 30, 15, and 7.5 g, respectively. The standard shape of capsules is traditional, symmetrical bullet shape. Some manufactures have employed distinctive shapes. e.g. Lillys pulvule tapers to a bluntly pointed end. Smith Kline Beachams spansule capsules taper at both the cap and body ends.
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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. 7) Storage : Finished capsules normally contain an equilibrium moisture content of 13-16%. To maintain a relative humidity of 40-60% when handling and storing capsules.
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Filling of hard gelatin capsules involves Equipment used in capsule filling operations
one often of two types of filling systems. Zanasi or Martelli encapsulator: Forms slugs in a dosatar which is a hollow tube with a plunger to eject capsule plug. Hofliger-Karg machine: Formation of compacts in a die plate using tamping pins to form a compact.
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ZANASI AUTOMATIC CAPSULE FILLING MACHINE

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HOFLIGER KARG AUTOMATIC CAPSULE FILLING MACHINE

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In this both system, the scale-up process involve bulk density, powder flow, compressibility, and lubricant distribution. Overly lubricated granules are responsible for delaying capsule disintegration and dissolution.

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OSAKA MODEL R-180 SEMI AUTOMATIC CAPSULE FILLING MACHINE

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I. Composition of the shell: Similar to hard gelatin shells, the basic component of soft gelatin shell is gelatin; however, the shell has been plasticized. The ratio of dry plasticizer to dry gelatin determines the hardness of the shell and can vary from 0.3-1.0 for very hard shell to 1.0-1.8 for very soft shell. Up to 5% sugar may be included to give a chewable quality to the shell. The residual shell moisture content of finished capsules will be in
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Manufacture of Soft Gelatin Capsules

II. Formulation : Formulation for soft gelatin capsules involves liquid, rather than powder technology. Materials are generally formulated to produce the smallest possible capsule consistent with maximum stability, therapeutic effectiveness and manufacture efficiency. The liquids are limited to those that do not have an adverse effect on gelatin walls. The pH of the lipid can be between 2.5 and 7.5. Emulsion can not be filled because water will be released that will affect the shell.
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The types of vehicles used in soft gelatin capsules fall in to two main groups: 1. Water immiscible, volatile or more likely more volatile liquids such as vegetable oils, mineral oils, medium-chain triglycerides and acetylated glycerides. 2. Water miscible, 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. All liquids used for filling must flow by gravity at a temperature of 350c or less. The sealing temperature of gelatin films is 37-400C.
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III. Manufacture process : A. Plate process : The process involved Placing the upper half of a plasticized gelatin sheet over a die plate containing numerous die pockets, Application of vacuum to draw the sheet in to the die pockets, Filling the pockets with liquor or paste, Folding the lower half of gelatin sheet back over the filled pockets, and Inserting the sandwich under a die press where the capsules are formed and cut out. University, NandedDept. of SRTM
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B. Rotary die press: In this process, the die cavities are machined in to the outer surface of the two rollers. 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. Two plasticized gelatin ribbons are continuously and simultaneously fed with the liquid or paste fill between the rollers of the rotary die mechanism. As the die rolls rotate, the convergence of the matching die pockets seals and cuts out the filled capsules.
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C. Accogel process: In general, this is another rotary process involving A measuring roll, A die roll, and A sealing roll. As the measuring roll and die rolls rotate, the measured doses are transferred to the gelatin-linked pockets of the die roll. The continued rotation of the filled die converges with the SRTM University, rotating sealing roll where a second gelatin sheet is applied to NandedDept. of form the other half of the capsule. 08 June 2009 83 Pharmaceutics

4. Bubble method: The Globex Mark II capsulator produces truly seamless, one-piece soft gelatin capsules by a bubble method.

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 A concentric tube dispenser simultaneously discharges the molten gelatin from the outer annulus and the liquid content from the tube. By means of a pulsating pump mechanism, the liquids are discharged from the concentric tube orifice into a chilledoil 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. The finished capsules must be degreased and dried.
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IV.

Soft/Liquid-filled hard gelatin capsules: Important reason: the standard for liquid filled capsules was inability to prevent leakage from hard gelatin capsules. As banding and of self-locking hard gelatin capsules, together with the development of high-resting state viscosity fills, has now made liquid/semisolid-filled hard gelatin capsules. As with soft gelatin capsules, any materials filled into hard capsules must not dissolve, alter or otherwise adversely affect the integrity of the shell. Generally, the fill material must be pumpable.
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 Three formulation strategies based on having a high resting viscosity after filling have been described. 1. Thixotropic formulations, 2. Thermal-setting formulations, 3. Mixed thermal-Thixotropic systems. The more lipophilic contents, the slower the release rate. Thus, by selecting excipients with varying HLB balance, varying release rate 08 June 2009 may be achieved.
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CAPSULE POLISHING MACHINE

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AUTO MATIC CAPSULE ARRANGEMNT

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