hard capsules Flashcards
how has hard capsules evolved over time?
gelatine- PEG-hpmc-enteric-pva
what are gelatine for hard capsules made from?
Fibrous protein, made from collagen Triple helix (quaternary structure). H-bonding/weak covalent bonds- animal skin, bones, hide, tendons.
how do you prepare gelatine for hard capsules?
- Size reduction, removal of meat, blood, fat etc
- Hydrolysis, denaturation of quaternary structure (reduce strength)
- Extraction, washing, sterilization
- Drying, size reduction and fractionation
what are gelatine capsules soluble in?
•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
what is the moisture content of gelatine?
Gelatin high moisture content (13-15 % w/w)
what happens if moisture is removed from gelatine capsules?
becomes brital and may break
or due to reaction with aldehyde groups (contents) or UV (cross linking)
what other materials can be used for hard capsuels?
•Hydroxypropylmethylcellulose (HPMC)(3-5 % w/w)
peg
Other materials = methylcellulose, starch, cross-linked dextrane, PVA (polyvinyl alcohol) copolymer (with acrylic acid and methyl methacrylate)
what may be added to hard capsules?
colours- usually for identification plasticisers- makes more flexible dyes or pigments surfactants flavours/sweetners surfactants
what is the most common cell size?
size 3
what does choice of capsule depend on?
tappened powder density
what will interparticular forces give?
-a larger difference between poured and tapped densities-increase in number of taps required to give tightest packing state
what is used to estimate powder flow?
Carr’s compressibility index and Hausner ratio use powder packing data to estimate powder flow
what does the hausner ratio indicate?
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
how do you calculate the capsule powder fill?
Capsule fill wt= tapped bulk density of formulation x capsule volume
how do you manufacture two-piece hard capsules?
- 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
how is the thickness of the shell goverened?
•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)
how is a capsule formulated?
- 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
how are capsules dried?
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)
how are casules removed?
the holder rotates against a knife that cuts the capsule to correct length
•gelatinis tough so needs sharp ceramic knife
during manufacturing what do they check in the samples?
- 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
how are capsules sorted?
•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
what is IPC- Capsule Moisture?
Measurement of the water activity inside the box.
Correlation with Official Loss on Drying used in QC for final release
what is IPC- External Diameters?
Go / No-go gauges with 0.01mm incrementsDiameter = smallest bore that the capsule passes through
how is capsule printing done?
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
why is capsule printing done?
•information examples: product name, strength, company details – allows identification
what process is the capsule printing done?
offset process-ink transferred to rubber offset roll, which prints onto capsules passing under the roll
what are the defects associated with capsules?
- 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
what are some of the print defects ?
unprinted
ink line/ spot
what are the two types of hard capsules?
- 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.
how are the powder formulated?
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
what is considered when choosing an appropiate filter?
Dose of drug•Particle size distribution•Particle shape•Solubility•Wetting properties•Stickiness/self-lubricating properties•Powder flow
how are capsules filled?
•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
what is Auger or screw filling?
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
what is Tamp filling?
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
what is Dosator filling?
- powder plug taken from bed and placed inside capsule
