HARD CAPSULES

Question 1

what is a capsule

Answer 1

an edible package made from gelatin or other suitable material and filled with a drug(s) to produce a unit dosage, mainly for oral
use.

Question 2

what is a hard gelatin capsule

Answer 2

r two-piece capsules which are composed of two pieces in the form of cylinders closed at one end. The shorter piece, called the “cap”, fits over the open end of the longer piece, called the “body”.

Question 3

Tablets are the most diffused dosage form among all. Capsules are the second. Nowadays, the ratio of capsules to tablets produced Worldwide is1-to-5.5.

Answer 3

one to five and a half ratio

Question 4

what are the advantages of capsules vs tablets

Answer 4

The formulation of capsules is somewhat easier, as there is no need to take into consideration the compactability of the powders or granules

Question 5

what is the main disadvantage of capsules vs tablets

Answer 5

its slower to produce

Question 6

what are the materials used in making hard capsules

Answer 6

1.gelatin (most common)

2.hydroxyppropyl methycellulose “HPMC”

Question 7

what are the advantages of HPMC

Answer 7

to produce a shell with low moisture content → this has a clear advantage so the material
loaded inside the capsules will be less exposed to moisture

Question 8

what are the content of a hard capsule shell

Answer 8

Gelatin
* Colourants
* Wetting agents
* Preservatives

Question 9

what is gelatin

Answer 9

semi natural
prepared by hydrolizing collagen
two types: A acidic hyrolysis(pork), and B alkali hydrolysis(beef bones)

Question 10

why is gelatin used a lot

Answer 10

Safety: it is non toxic, widely used in foodstuffs andacceptable for use worldwide. * Solubility: it is readily soluble in biological fluids at bodytemperature. * Film forming properties: it is capable of producing strongflexible films (Thickness of the wall of a hard gelatin capsule isonly about 0.1 mm).

Question 11

what are the colourants types

Answer 11

• Water soluble dyes
• Water insoluble pigments (pigments are preferred becausethey are not absorbed on ingestion- less risk of toxicity)
   To prepare the range of colours seen in the capsules, dyes andpigments are mixed together in solutions or suspensions

Question 12

what is the use of Titanium dioxide

Answer 12

used as an opacifier to make the capsuleopaque (and white)

Question 13

what are the function of wetting agents in the shell formulation (not more than 0.15% sls

Answer 13

ensure that the lubricated metal moulds areuniformly covered when dipped in the gelatin solution, duringmanufacturing of the gelatin shells.

Question 14

why were preservatives used before in the foramlation of the shells

Answer 14

added to hard capsules to preventmicrobial contamination.
 Hard gelatin capsules contain between 13 and 16% w/v ofmoisture. However, because the moisture is strongly bound tothe gelatin molecules, gelatin usually doesn’t support microbial
growth.

Question 15

what is the process of manufacturing shells

Answer 15

1st step - Preparation of the raw materials
 A concentrated solution of gelatin 35-40% is prepared using demineralized hot water 60-70°C. This is stirred until gelatin is dissolved and then a vacuum is applied to remove any entrapped air bubbles. The required amounts of dye solution and pigment suspension are added.
 The viscosity of the gelatin solution is measured and adjusted to a target value by addition of hot water. Viscosity is important to control
the thickness of the capsule shells during production. The higher the viscosity the thicker the shell wall produced

2nd step – Dipping
 The gelatin (coloured) solution is passed into the Capsule machine.
 The machine consists of two mirror image halves one for the cap and the other for the body.
 The moulds which are known as ‘pins’ are made of stainless steel and are mounted in sets on metal strips, called ‘bars’.
 Capsules are formed by dipping sets of moulds, which are at room temperature 22°C, into a ‘dip pan’ that holds a fixed quantity of gelatin solution having a constant temperature of 45-55°C.
 A film is formed on the surface of each mould by gelling

3rd step – Spinning
 The moulds are slowly withdrawn from the solution and then rotated during their transfer to the upper level.
 This is done in order to:
1. uniform the film
2. avoid the formation of a bead at the capsule ends

4
h step – Drying
 The pin bars are allowed to dry in the upper level of the machine.
 Further drying is achieved by transfer to the lower level.
 Drying is achieved by blowing large volumes of air at low humidity over the moulds.

5th step – Stripping

6th step – Cutting
 The dried films are then cut to the correct length (a maximum±0.15 mm tolerance is allowed).

7th step – Joining
 The two parts joined together and the complete capsules delivered from the machine

Question 16

what are the available sizes for capsules

Answer 16

000 and 00 too big for human

0-4 for humans

5 for rodents

size depends on density

Question 17

what is the used shape after 1960s

Answer 17

To ensure reliable closing of the filled capsules,
capsule shells with locking grooves (or
indentations) have been prepared. The two
grooves fit into each other for tight closing and
prevent accidental separation (or splitting) of
the capsules.
 These capsules have a series of indentations
on the inside of the cap and on the external
surface of the body which (when the capsule
is closed after filling) form an interference fit
sufficient to hold them together during
mechanical handling.

Question 18

how does moisture effect gelatin caps

Answer 18

usually has 13-16%

hpmc has 3%-6%

At low relative humidity, moisture is lost and the capsule becomes brittle.Moreover, hygroscopic formulations can absorb water out of the shell
leading to brittleness and drying-out of the shell. * At high humidity levels they will gain moisture and soften.
 In order to maintain the moisture content constant (so to prevent unwanted cracking or softening of capsules) should be stored in sealed container.

Question 19

what are the limitations to filling capsules

Answer 19

Must not react with gelatin (e.g. formaldehyde causes
crosslinking reaction that makes the capsule insoluble). * Must not interfere with the integrity of the shell (materials with high level of free water, that can be absorbed by gelatincausing it to soften). * In case of low density formulation, large doses cannot be used.

Question 20

what are the types of fillings

Answer 20

 Dry solids: Powders, Pellets, Granules, mini-tablets, mini-capsules.

 Semisolids: * Thermosoftening mixtures (during filling are in the molten state and fluid enough to be pumped and filled). On standing solidification happens. E.g. PEG 4000, solid fat. * Thixotropic mixtures: thin with low viscosity upon shearing by mixing and form hard mass with high viscosity upon standing when shearing ceases. During filling they are fluid and semisolid during shelf life.

 Liquids: Non-aqueous liquids: requires sealing by applying gelatin solution at the cap-body joint to form sealing gelatin band upon drying. If not sealed leakage at the joint will happen during handling. Sealing also reduces oxygen permeation into the content, protecting them from oxidation

Question 21

what is bench scale filling
dose depended

Answer 21

are used to filled small quantities of capsules
 are used only for extemporaneous compounding (hospital andcommunity pharmacy) and in the industry for clinical trails.
 They generally consist of sets of plastic plates with pre-drilled holes to take from 30-100 capsules of a specific size.

1. The bodies are locked in their plate by means of a screw and the caps in their plate are removed.
2. The powder is placed onto the surface of the body plate and is spread with a spatula so that it is filled into the bodies.
3. The cap plate is then repositioned over the body one and the capsules are rejoined using manual pressure.
    The uniformity of fill weight is very dependent upon good flow properties of the powder.

Question 22

what is industrial scale filling

Answer 22

Machines for the industrial-scale filling of hard capsules come in agreat variety of shapes and sizes, varying from semi- to fullyautomated and ranging in output from 3000 to 150000 per hour.

Question 23

what are the types of industrial filling

Answer 23

1. Dependent: which use the capsule body directly to measure the powder.
2. Independent: where the powder is measured independently of the body in a special measuring device.

Question 24

what are the dose dependent auger system

Answer 24

3 stations

Station 1, for capsuled feeding and opening: Empty capsules are fed into a pair of ring holders, the caps being retained in one half and the body in the other.

Station 2, for capsule filling:
The two holders (stuck together) are moved from station 1 to a revolving turn-table (station 2).The caps holder (upper) is removed from the table (1).
The powder hopper is pulled over the lower holder, which rotates underneath, filling thepowder into the capsule bodies (2).
The upper holding ring and lower holding ring are put back together (3)The filling of powder through the hopper into
the capsule bodies must be very rapid for this
reason inside the powder hopper an auger
forces the powder down.

Station 3, for capsule closure and ejection:
 The two assembled holders are moved from station 2 to the ejector(station 3) (1).
 Here metallic pins push the bodies into the caps (closing the capsules-2)and induce ejection of the capsules from the holder (3).

 The weight of powder filled into the body is dependent on the timethe body is underneath the hopper during the revolution of the plateholder.
 The dependent dosing systems are semiautomatic in operation,requiring an operator to transfer the capsule holder from oneoperation to the next.
 The output from such machines varies between 15,000 and 25,000per hour and is dependent on the skill of the operator.
 Relatively old technology, still in use in many developing countriesand they are used by the herbal and supplements industries.

Question 25

what is dose independent filling

Answer 25

Fully automatic systems. Use a dosing mechanism that forms a ‘plug’ of powder that is transferred then to the capsule shell. Plugs are soft compacts formed at low compression forces (10-100 N). Plugs are soft because they are not the final dosage form, unlike tablets, as they will be contained inside a capsule shell.

Question 26

what are dosators dose independented

Answer 26

These consist of a dosing tube inside which there is a movable spring-loaded piston, thus forming a variable-volume chamber in the bottom of the cylinder. 1. Initially the tube is lowered open end into a bed of powder. 2. As the powder enter the tube and fill the chamber it forms the plug (i.e. the powder become slightly compressed). 3. The plug may be further consolidated by applying acompression force with the piston. 4. The assembly is then raised from the powder bed andis positioned over the capsule body. 5. The plug is then ejected into the capsule body by lowering the piston. The weight of powder filled for a certain formulation depends on: 1. The initial height of the piston 2. The height of the powder bed loaded in the machine This system is the most widely used and its output ranges from 3000 to 150000 capsules filled per hour.

Question 27

what are tamping finger and dosing disc system

Answer 27

The dosing disc forms the base of the dosing or filling chamber. The dosing disc has a series of accurately drilled holes in which powder plugs are formed by several sets of tamping fingers (stainless steel rods).  At each position the fingers push (compress) material into the holes, building up a plug. The plug is moved to next finger by the movement of the dosing disc. By the action of several fingers in sequence, an increasingly higher plug is formed. At the last position the finger pushes the plug through the disc into a capsule body The powder fill weight can be varied: 1. by the amount of insertion of the fingers into the disc (i.e. by how much the fingers are lowered into the holes), 2. by changing the thickness of the dosing disc, 3. by adjusting the amount of powder in the dosing chamber.

Question 28

what is in the powder formula

Answer 28

Diluents: give plug forming properties. Lubricants: reduces powder to metal adhesion. Glidants: improve powder flow. Wetting agents: improve water penetration. Disintegrants: produce disruption of powder mass.

Question 29

whats in the drug formula

Answer 29

Low-dose potent drugs are the easiest to formulate for capsulefilling. In this case the drug occupies only a small percentage ofthe total formulation (<20%) and so the properties of the mixturewill be governed by the excipients chosen. On the other hand, in case of high dose drugs (500mg of anantibiotic or paracetamol), the excipients must be chosencarefully to exert their effect at low concentrations (<5%) and theproperties of the mixture will be governed by that of the activeingredient

Question 30

what is a diluent

Answer 30

Give plug forming properties. Should have the following ideal properties: Good flow: obtainable using free flowing diluents and glidants. Cohesion: important for plug formation; diluent should be compressiblediluents.* *Note 1: this is only important when independent dosing systems for filling thecapsules (based on plug formation) are used, but not for dependent dosingsystem. *Note 2: compressibility of the powder formulation should be good enough toform a soft plug, yet not too high: in fact, hard plug can result in too slowdisintegration and dissolution. (Remember: a plug is not a tablet). For water insoluble hydrophobic drugs, water soluble diluents,such as lactose is chosen, because it will improve drug dissolutionand bioavailability. → The soluble diluent will make the powder mass filled insidethe capsule more hydrophilic, thus facilitating its break upafter the capsule shell has dissolved. Most commonly used diluents in capsules are: lactose,microcrystalline cellulose, starch 1500.

Question 31

what are glidants

Answer 31

 Uniform filling of capsule bodies is mainly dependent on good powder flow.  Glidants reduce inter-particulate friction, such as colloidal anhydrous silica, and talc.  Low dose actives can be made to flow well by mixing them with free-flowing diluents. And thus glidant is usually not necessary in this case.  For high dose drugs, because little space is available for diluent addition, and flowability is governed by the drug; glidant addition is usually a must.

Question 32

what are lubricants

Answer 32

Lubricants: reduce powder to metal adhesion, such asmagnesium stearate.  Lubricants are usually hydrophobic materials that achieve theiractivity by coating the surface of pharmaceutical powders.  At high levels they can reduce the solid mass wettability andthus reduce dissolution rate and drug release frompharmaceutical solids.

Question 33

what are disintegrants

Answer 33

 Disintegrants are required to break filled powder mass into primarypowder particles.  In the past disintegrants were not added into capsules, becausethe conventional disintegrant used in tablets (i.e. starch) does notwork well in capsules. This is because the plug is less compactedand more porous than the tablet and the starch does not swell enough to fill all the pores and break the plug.  The modern superdisintegrants swell more and are often usedtoday inside capsules formulations (Sodium Starch glycolate andCrospovidone and Croscarmellose sodium)

Question 34

what are wetting agents

Answer 34

 Are used when the drug is poorly soluble and hydrophobic.They reduce interfacial tension between drug particles and theaqueous dissolution medium, promoting solvent penetrationand wettability.  Sodium lauryl sulphate at levels of 1% in combination with awater soluble diluent has been shown to increase dissolutionrate of poorly soluble drugs.