MANUFACTURING OF CAPSULE

RAHUL MISHRA-

BENGAL SCHOOL OF TECHNOLOGY

(A COLLEGE OF TECHNOLOGY) 

                                                             

                                                               INTRODUCTION:

In pharmaceuticals, encapsulation means that most of the doses used to bind drugs are in a relatively stable cover known as shape technique capsules, which allow their use, for example, orally or as a suppository. Give permission There are two main types of capsules:

• Hard capsules: dry, powdered substances or microparticles such as. The extrusion or 

spironization process. They are made in two parts: a "body" of small diameter that is 

filled and then sealed with a "cover" of large diameter.

• Soft capsules: they are mainly used for oils and active ingredients that dissolve or 

suspend in oil.

Both kinds of capsules are made of aqueous solutions of gelling agents, such as animal 

proteins (mainly gelatin) or vegetable polysaccharides or their derivatives. Other 

ingredients may be added to the gelling agent solution, including plasticizers such as 

glycerin or sorbitol to reduce the hardness of the capsule, coloring agents, preservatives,

disinfectants, lubricants and surface treatments.

                        

FEATURE OF HARD GELATIN CAPSULE

ADVANTAGES OF CAPSULES FOR ORAL ADMINISTRATION:

• Easy to swallow thanks to its soft and slippery nature.

• Easy to handle and transport.

• Can mask the unpleasant taste, color and smell of the drug by using an insipid shell

• Better bioavailability than tablets and a faster onset of action than tablets.

• The shells are physiologically inert and are digested easily and quickly in the gastrointestinal tract.

• The housings can be opacified (with titanium dioxide) or colored to protect them from light.

DISADVANTAGES OF CAPSULES:

• Bulky materials can give a large capsule size.

• The ingredients may interact with the capsules.

• Limited filling weight based on capsule volumes.

• It is known that there is a variation in the filling volume.

• It can cost more.

• Soft gel content limited to an adjusted pH range.

     MANUFACTURE OF HARD GELATIN GELATIN CAPSULES

Steps involved in making empty gelatin capsules

·        Dipping

·        Spinning

·        Drying

·        Stripping

·        Trimming and joining

·        Polishing

1. Dipping: Pairs of the stainless steel pins are dipped into the dipping solution to simultaneously form the caps and bodies. The dipping solution is maintained at a temperature of about 50°C in a heated, jacketed dipping pan.

2. Spinning: the pins are rotated to distribute the gelatin over the pins uniformly and to avoid the formation of a bead at the capsule ends.

3. Drying: the gelatin is dried by a blast of cool air to form a hard shells. The pins are moved through a series of air drying kilns to remove water

4. Stripping: a series of Bronze jaws strip the cap and body portions of the capsules from the pins.

5. Trimming and Joining: the stripped cap and body portions are trimmed to the required length by stationary knives. After trimming to the right length, the cap and body portion are joined and ejected from the machine.

SPECIFICATION:

SIZE OF CAPSULES:-

*The very large size of the capsule is No: 000

*The very small size is No: 5

*The normal shape of capsules is traditional, symmetrical bullet shape

RECTIFICATION:

·        The empty capsules are oriented so that all points are oriented in the same direction, that is, the body ends at the bottom.

·        In general, the capsules pass one at a time in a channel wide enough to allow good adhesion at the end of the lid.

·        Capsules The capsules will always be aligned from end to end, regardless of the end that enters the channel first with specially designated blades.

 SEPARATION OF CAPS FROM BODY:

·        Capsules Rectified capsules come with the body end first in the top of the divided capsules or split filling rings.

·        A vacuum applied from the bottom pulls the body down at the bottom of the split ring.

·        Diameter The diameter of the bush is too large to allow it to follow the body.

·        Bush Split rings are separated to expose bodies for filling 8.

 FILLING OF POWDER FORMULATIONS:

·        Bench -Scale Filling

·        Industrial -Scale Filling

Ø Dependent dosing system 

Ø Independent dosing system

CAPSULE FILLING:

·       Auger:

Ø Semi -automatic operation

Ø Filling based on volume

Ø Need good powder flow properties

·       Dosator:

Ø Fill based on weight

Ø Continuous operation

·       Dosing disc:

Ø Filled based on weight

Ø Continuous operation

SEMIAUTOMATIC CAPSULE MACHINE

a)     Sandwich of cap and body rings positioned under rectifier to receive empty capsules. Vacuum is pulled from beneath the rings to separate caps from bodies.

b)    Body ring is positioned under foot of powder hopper for filling

c)     After filling the bodies, the cap and body rings are re-joined and positioned in front of pins. These pins push the bodies to engage the caps

d)    The plate is swung aside and the pins are used to eject the closed capsules

FILLING -VIBRATORY FILL PRINCIPLE

·        In the powder, a perforated resin plate is positioned and connected to a vibrator

·        The powder blend tends to be fluidized by the vibration of plate and assists the powder to flow into the bodies through the holes in resin plate 11

CLEANING AND POLISHING CAPSULES

• A small amount of powder can adhere to the outside of the capsules after filling.

1. Frying pan polishing: due to its unique design (mainly in the area of ​​air flow), the Accela-Cota tablet coating tray can be used to dust and turn it into a capsule.

2. Brushing: in this procedure, the capsules are fed with soft rotating brushes that serve to remove dust from the capsule shell.

3. Cloth dusting: In this method, the filled capsule is rubbed with a cloth impregnated or not with an inert oil.

CAPSULE POLISHING AND CAPSULE INSPECTION MACHINE

STORAGE, PACKAGING, AND STABILITY

• The finished capsules normally contain an EMC of 13 to 16%.

• <12% MC, capsule layers become fragile

• >18% make them too soft

• Maintain a relative humidity of 40 to 60% when handling and storing capsules.

• QUALI-V, developed by Shionogi Qualicaps, is the first HPMC capsule developed for eventual use in pharmaceutical products.

EVALUATION OF CAPSULES:

·        Disintegration test

·        Dissolution test

·        Content uniformity

·        Weight variation

INSPECTING:

·        Visual or electronic inspection -uniform in appearance

·        Counting

·        Counting tray

·        Counting or filling machine

·        Packaging

·        Unit dose and strip packaging

·        Sanitary, identifiable, safe

·        Storing

·        In a tight closed container in a cool dry place

RECENT FILLING EQUIPMENTS:

·         Roto- fill: - 2lakh capsules/day

·         Acco -fill: - 75,000 capsules/hr

·         Roto-weigh

·         Roto-sort: - 1,50,000 capsules/hr

SOFT GELATIN CAPSULE

A soft gel or soft gelatin capsule is a solid capsule (outer shell) that surrounds a liquid or semi-solid center (inner filling). An active ingredient can be incorporated into the outer shell, the internal charge or both. They are an oral dosage form for capsule medicine. The soft gel layers are a combination gelatin, water, opacifier and a plasticizer such as glycerin and / or sorbitol (s). 

                  FORMULATION OF SOFT GELATIN CAPSULES:

Plasticizers:

These are used to make the soft gel shell elastic and pliable. They usually account for 20-30%.The most common plasticizers used in soft gels is  glycerol,  although  sorbitol  and  propyleneglycol-400  are  used  frequently  often  in combination  with  glycerol.  The  amount  and choice  of  the  plasticizer  contribute  to  the hardness  of  the  final  product  and  may  even affect  its  dissolution  or  disintegration characteristics,  as  well  as  its  physical  and chemical stability. One of the most important aspect of soft gel formulation is to ensure that

There is minimum interaction or migration between the liquid fill matrix and the soft gel shell.  The  choice  of  plasticizer  type  and concentration  is  important  in  ensuring optimum  compatibility  of  the  shell  with  the liquid fill matrix.

Water: The other essential component of the soft gel shell is water. Water typically accounts for between 30 and 40% of the wet gel formulation and its presence is important to ensure proper treatment during gel preparation and capsule capsulation. In dry gels, the equilibrium water content is generally between 5 and 8% w / w, which represents the proportion of water bound to the gelatin in the flexible gel envelope. This level of water is important for good physical stability, because in difficult storage conditions, the soft gels will either become too soft and fuse together, or too hard and fragile. Dyes / Opacifiers: Dyes can be synthetic or natural and are used to impart the desired shell color for product identification. An opacifier, generally titanium dioxide, may be added to produce an opaque shell when the fill formulation is a slurry or to prevent photodegradation of the light-sensitive filler ingredients. 

Titanium dioxide can be used alone to produce a white opaque shell or in combination with pigments to produce a colored opaque shell.

preservatives:

Preservatives are used to preserve the drug from microbes. It is used about 0.2% of the total concentration of the drug. Methylparaben and propylparaben are mainly used as preservatives.

 Flavoring agents:

Flavoring agents are used for taste

Hiding. Ethyl vanillin, essential oils and

Different sugars, mainly sucrose, are also used flavouring agent

FEATURE OF SOFT GELATIN CAPSULE

Advantage of soft gels

·        Easy to swallow, no taste, temper proof.

·        Wide variety of colors, shapes, and sizes.

·        Accommodates a wide variety of compounds filled as a semi-solid, liquid, gel or paste.

·        Immediate or delayed drug delivery.

·        Can be used to improve bioavailability by delivering drug in solution or other absorption enhancing media.

Disadvantages of soft gels

 Requires special manufacturing equipment.

· Stability concerns with highly water soluble compounds, and compounds susceptible to hydrolysis.
· Limited choices of excipients/carriers compatible with the gelatin

Outer shell of soft gels

The outer shell is composed of a gelatin or potato starch matrix. Gelatin matrix consists of gelatin, plasticizer, solvent and optional ingredients such as flavours and colorants.

MANUFACTURING OF SOFT GELATIN

CAPSULE:

Following methods are used:

1. Plate process

2. Rotary die process

3. Reciprocating die process

4. Accogel process

5.     Seamless gelatin capsules

1. Plate process:           

In this process a warmed sheet of gelatin sheet is placed over a die plate having a number of depression or moulds or numerous die pockets. The sheet is drawn into these depressions or pockets by applying vacuum.  A measured quantity of liquid medicament is pour over it. Over this another plate of the mould is placed and the pressure is then applied to the combine plate.  The capsules are then simultaneously shaped, filled, sealed and cut into individual units.  This method is uses for small scale preparation of soft gelatin capsules. It has 20-40% of net moisture content.

2. Rotary Die process: Two ribbons of gelatin are fed continuously into a rotating die assembly and are simultaneously formed into the two halves of a capsule. The ribbons converge adjacent to a fill injector. The fill injector is actuated by a pump which measures and dispenses the appropriate volume of fill material into the capsules. The filled capsules are subsequently sealed as the die assembly rotates. This process permits accurate and reproducible fill uniformity. Pump heads are available for fill weights as low as 100 mg. For oral dosage forms, the fill weight ranges from 100 mg up to about 1 gram.

The following should be monitored/controlled:
· Gelatin temperature
· Fill temperature
· Ribbon thickness
· Seal or seam width
· Fill quantity

Following encapsulation, the capsules undergo drying in a tumble drying tunnel with an elevated temperature and a large volume of forced air. From the drying tunnel, the capsules are transferred onto trays and placed into a low humidity drying room.

The following should be monitored:

1.     Gelatin moisture

2.     Fill moisture

3.     Capsule hardness

Drying:-

Drying is a dynamic process, whose objective is to bring the gelatin shell to a moisture content of equilibrium between 6 and 8%.The oil dries quickly faster than PEG and generally reaches 6-8% moisture in the deposits in 24 hours.If the water migrates to the embankment, it must return at least or be at least in balance with the moisture content of the hull for good stability. This is more typical of PEG fillers. These can take 7 to 10 days to reach acceptable humidity levels, and can still retain up to 10% water after drying.

Finishing:-

After drying, the soft gels are classified (sized), polished, printed and quality inspected. Soft gels are packaged in suitable containers, usually low density polyethylene (LDPE) bags, vials or high density polyethylene (HDPE) ampoules. The recommended storage conditions for soft gels include a temperature range of 15 to 300 ° C and a relative humidity of 50% maximum. When stored under these conditions, the equilibrium moisture content of the cover material and oxygen permeability through the material are minimal, which improves the stability of soft gel products.