hard capsules

Question 1

how has hard capsules evolved over time?

Answer 1

gelatine- PEG-hpmc-enteric-pva

Question 2

what are gelatine for hard capsules made from?

Answer 2

Fibrous protein, made from collagen 
Triple helix (quaternary structure). H-bonding/weak covalent bonds- animal skin, bones, hide, tendons.

Question 3

how do you prepare gelatine for hard capsules?

Answer 3

• Size reduction, removal of meat, blood, fat etc
• Hydrolysis, denaturation of quaternary structure (reduce strength)
• Extraction, washing, sterilization
• Drying, size reduction and fractionation

Question 4

what are gelatine capsules soluble in?

Answer 4

•Soluble in acid environment of stomach•Solution gives suitable viscosity (colloidal solution) with thermally reversible gelation properties•Films are clear, strong, flexible and high gloss

Question 5

what is the moisture content of gelatine?

Answer 5

Gelatin high moisture content (13-15 % w/w)

Question 6

what happens if moisture is removed from gelatine capsules?

Answer 6

becomes brital and may break

or due to reaction with aldehyde groups (contents) or UV (cross linking)

Question 7

what other materials can be used for hard capsuels?

Answer 7

•Hydroxypropylmethylcellulose (HPMC)(3-5 % w/w)
peg
Other materials = methylcellulose, starch, cross-linked dextrane, PVA (polyvinyl alcohol) copolymer (with acrylic acid and methyl methacrylate)

Question 8

what may be added to hard capsules?

Answer 8

colours- usually for identification
plasticisers- makes more flexible
dyes or pigments
surfactants
flavours/sweetners
surfactants

Question 9

what is the most common cell size?

Answer 9

size 3

Question 10

what does choice of capsule depend on?

Answer 10

tappened powder density

Question 11

what will interparticular forces give?

Answer 11

-a larger difference between poured and tapped densities-increase in number of taps required to give tightest packing state

Question 12

what is used to estimate powder flow?

Answer 12

Carr’s compressibility index and Hausner ratio use powder packing data to estimate powder flow

Question 13

what does the hausner ratio indicate?

Answer 13

value less than 1.25 indicates good flow (= 20% Carr),value greater than 1.5 indicates poor flow (=33% Carr).between 1.25 and 1.5, added glidantnormallyimprovesf low.>1.5 added glidantdoesn’t improve flow

Question 14

how do you calculate the capsule powder fill?

Answer 14

Capsule fill wt= tapped bulk density of formulation x capsule volume

Question 15

how do you manufacture two-piece hard capsules?

Answer 15

• stock solution preparede.g. gelatin& additives
• Gelatindissolved (30-40% w/w) in hot (60-70oC) distilled water. Vacuum applied to removed bubbles of air.
• in hot solution, gelatinhydrolyses & viscosity gradually decreases therefore small batches prepared to minimise this
• colourantsadde

Question 16

how is the thickness of the shell goverened?

Answer 16

•thickness of capsule shell governed by viscosity (changes as water lost by evaporation – must be taken into account i.e. may have to reduce viscosity of batches made earlier)

Question 17

how is a capsule formulated?

Answer 17

• stainless steel mould pins dipped into solution (50-55oC) – slowly lowered then slowly withdrawn
• solution in jacketed vessel, with constant stirring
• pins are set in line on metal bars -pin bar. Also lubricated with release oil(pins for body are longer)
• capsule shells are slightly tapered towards closed end
• film formed on surface of each mould by gelling
• pins removed from solution and rotated about a horizontal axis to spread gelatin evenly over the pins
• stream of cool air helps set the gelatin

Question 18

how are capsules dried?

Answer 18

pin bars passed through a series of drying kilns – air at 22-28oC•target moisture content at this stage is 15-18 %w/w (to facilitate removal)

Question 19

how are casules removed?

Answer 19

the holder rotates against a knife that cuts the capsule to correct length
•gelatinis tough so needs sharp ceramic knife

Question 20

during manufacturing what do they check in the samples?

Answer 20

• length of cap & body, cap & body diameter, closed joined length
• thickness of capsule wall and end wall (dome). Capsule flattened in measuring gauge
• weight
• moisture content

Question 21

how are capsules sorted?

Answer 21

•empty shells are sorted by placing them on plates with holes. Unacceptable capsules (damaged) cannot pass through holes
.•sorting may also be done by directing a beam of light at capsule, defects would scatter light and activate a rejection process

Question 22

what is IPC- Capsule Moisture?

Answer 22

Measurement of the water activity inside the box.

Correlation with Official Loss on Drying used in QC for final release

Question 23

what is IPC- External Diameters?

Answer 23

Go / No-go gauges with 0.01mm incrementsDiameter = smallest bore that the capsule passes through

Question 24

how is capsule printing done?

Answer 24

insoluble pigments (iea suspension in the vehicle chosen), dispersed in volatile solvent containing a film forming polymer (usually shellac)•pigments e.g. carbon, iron oxides, titanium dioxide•usually on empty capsules

Question 25

why is capsule printing done?

Answer 25

•information examples: product name, strength, company details – allows identification

Question 26

what process is the capsule printing done?

Answer 26

offset process-ink transferred to rubber offset roll, which prints onto capsules passing under the roll

Question 27

what are the defects associated with capsules?

Answer 27

* critical defects * usually cause filling problems –too short, too long, squashed, holes, cracks and flat areas * major defects * cause a problem in use and reduce effectiveness of filled capsule –separated capsules, thin walls & splits * minor defects * do not affect performance, but spoil appearance – surface blemishes such as pits, bubbles & specks

Question 28

what are some of the print defects ?

Answer 28

unprinted | ink line/ spot

Question 29

what are the two types of hard capsules?

Answer 29

* self-locking capsules– prevent capsules opening. Features moulded into cap & body e.g. Posilok(Qualicaps), Coni-snap (Capsugel). Prelockfeature keeps parts together before filling. •Air venting is needed when capsules closed to prevent pressure build up – achieved by having grooves on body * capsules for liquid fill– either liquids mobile at ambient temperature or semi-solid matrix formulations. Must prevent leakage – open end of body must push in and make contact with dome of capsule. Use sealing liquid or layer of gelatin(called banding) at join.

Question 30

how are the powder formulated?

Answer 30

Drug – particle size important, dissolution rate. Poorly soluble drugs mixed with soluble diluents. Soluble drugs may be mixed with insoluble diluents e.g. starch•Low dose drugs mixed with diluents (fillers) e.g. lactoseTightly packed powder (high bulk density) may dissolve more slowly.•Glidantsto improve flow (reduce interparticulatefriction) e.g. silica dioxide, and lubricants (reduce powder/metal adhesion) e.g. magnesium stearate (hydrophobic) or sodium stearylfumarate(hydrophilic)•Disintegrating agents e.g. sodium starch glycollate

Question 31

what is considered when choosing an appropiate filter?

Answer 31

Dose of drug•Particle size distribution•Particle shape•Solubility•Wetting properties•Stickiness/self-lubricating properties•Powder flow

Question 32

how are capsules filled?

Answer 32

•machines developed for industrial use automatically:•separate the caps from the empty capsules, •fill the bodies, •scrape off the excess powder,•replace the caps, seal the capsules as desired,•clean the outside of the filled capsules •at up to 165,000 capsules per hour. •the dosing mechanisms either:•dependent type (powder filled directly from hopper into capsule) machines e.g. Auger (screw) •independent type machines e.g. the Dosator& Tamp filling

Question 33

what is Auger or screw filling?

Answer 33

powder/granules in hopper. Inside is rotating screw which feeds powder into capsule body. Empty capsules are rotated beneath and filled. Powder fill mass depends on rotation rate & screw design

Question 34

what is Tamp filling?

Answer 34

powder fills up cylindrical holes in dosing disc and metal rods compress powder to form plugs. Disc rotating and when positioned above capsule, plug is pushed into body. Some tamping machines can fill 150,000 capsules per hour

Question 35

what is Dosator filling?

Answer 35

- powder plug taken from bed and placed inside capsule