9. Hard and soft gelatin capsules

rivubako's version from 2017-02-18 11:28

Section 1

Question Answer
advantages of hard and soft gelatin capsules?good for taste and odour masking, attractive, easy to administer, mechanically strong but flexible, fewer ingredients, good bioavailability
why do capsules have greater bioavailability?gelatin shell dissolves in GI tract in 2 mins leaving powder plug which if a wetting agent is added will be penetrated v quickly, already in finely divided state the drug will dissolve quickly and be readily absorbed, bioavailability may be further increased by filling capsules with liquids, bioavailability may be modified by coating with polymers or an enteric to modify rate of release
disadvantages of capsules?rate of capsule filling slow, unless considerable care in taken poor weight uniformity can result, high cost of equipment
why are capsule shells nearly always made of gelatin?non toxic, ready sol in biological fluids, good film forming material, natural substance, though synthetic HPMC substitute available
what is bloom strength?measure of gel rigidity
what is the bloom strength test?the force in grams to push a standard 12.7mm plunger a distance of 4mm into a standard 6.67%w/v gelation solution, 16-18h after manufacture at 10oC. it must be high for HGCs (approc 200-250g) & lower for SGCs (150g)
why is viscosity important?will determine film thickness. thicker visc=thicker capsule
what are HGCs made of?1. bone gelatin for toughness, 2. pork skin gelatin for plasticity & elasticity though HPMC is an alternative. 3. glycerol or propylene glycol as a plasticiser to ensure remains flexible (more important in SFCs), 4. preservatives as gelatin capsules have 13% moisture content, 5. colours/opacifiers, 6.water important as an alternative to a plasticiser, lower conc will cause brittleness, high conc soft and weak
how are capsule shells manufactured?comprised of two pieces, one part is slightly narrower and longer than the other. A mould is dipped into a gelatin solution to form the two halves before drying, stripping from the mould and joining.
the size of the capsule required is determined by?caps fill weight=tapped bulk density x caps vol

Section 2

Question Answer
what may capsules be filled with?powders, granules,pellets, semi-solids, liquids
what are typical ingredients of powder filled capsules?diluent (soluble for insoluble API for fast dist, less soluble for soluble API to avoid competition for solute), glidant, lubricant, wetting agent
typical ingredients of granule filled capsules?API+diluent+wetting agent granulated with suitable binder/granulating fluid. once dried blended with glidant & lubricant. disintegrants rarely used
pellets are...exceptionally free flowing, do not exhibit any cohesion, cannot be compressed, different filling mechanism
filling mechanism for pellets?Double slide mechanism: pellets 1st flow from a hopper into dosing chamber, chamber closed off from the hopper with the dosing slide, outlet slide is opened above the capsule body and the pellets flow into it, process repeated.
filling mechanism for tablets?used for special release. special hopper used to drop tablet/s into lower half before it continues with the further filling, capsules can therefore contain a mix of small tablets with powder, granules or pellets
filling mechanism for liquids & semisolids?semi solids can be packed into HGCs. must be thermosoftening (API dispersed in hot melted polymer such as PEG which will solidify when cool) or thixotropic (API dispersed in thixotropic base which is liquid during filling but will solidify when shearing has stopped. both types are filled into capsules using the metered pump device
capsule formulation examples?capsules filled with coated granules: Vanlafaxine, antidepressant released via diffusion through coating. Capsules filled with pellets: morphine sulphate- Avinza. Capsules filled powders: Celebrex
capsule shell filling equipment positions capsules by?the principle that capsules will automatically fall the right way up if they are allowed to fall into a channel that is of a diameter slightly greater than the bottom shell of the capsule and slightly narrower than the top half.
capsule shell filling equipment separate the two halves by?lightly gripping the bottom half & using a vacuum system to remove the top
after the 1/2s are sepereated capsule shell filling equipment....fills the lower 1/2 with formulation, replaces the cap on the body allowing air to escape before the 2 1/2s are locked together.

Section 3

Question Answer
what is the Flooding method of capsule filling?lab based, formulation must flow uniformly & easily. The empty capsules are placed on the capsule filler, the capsule filler in shaken to move the capsules into the grooves, powder is added to the empty capsule bases, the powder is distributed equally, the caps are joined to the bases and removed
what is the plugging method of capsule filling?most widely used system, comprises of a dosing tube containing a spring loaded plunger. important that powder/granules are cohesive as efficient flow would result in powder loss from dosator during transfer
what is the Vacuum method of capsule filling?similar to plugging, powder held in dosator by -ive pressure, when positioned over capsule body compressed air is used to expel powder plug, cohesive not required
what is the Tamping method of capsule filling?used for poor flowing powder, machine provides a tamping or auger device which forces the powder into the capsule body.
what is the Locking method of capsule sealing?2 series of indentations formed on shell during formation the 1st of which holds 2 1/2s together loosely during transport, the 2nd 2 lock the 2 together after filling
what are the other methods of capsule filling?spot welding, banding (band of molten gelatin formed around the join)
what tests are part of capsule final product testing?content of active ingredient of capsules, uniformity of mass, disintegration test for capsules, dissolution rate of capsules, also often appearance testing
what are the packaging requirements for capsule products?HGCs and SGCs must be stored in containers that are impervious to moisture, stored in tightly closed containers, away from direct sunlight, less than 25oC and rel humidity under 60%, typically stored in blister packs

Section 4

Question Answer
advantages of SGCsmore appealing due to ease of swallowing, absence of taste & convenience, greater bioavailability reduces dose required and so size required
SGCs are used for?lipophillic liquids
what is the Globex method of SGC encapsulation?gelatin solution maintained at approx 80oC in 1 tank & the excipient solution in other, both pulse pumped simultaneously through a double dosing tube with gelatin sol around outside, the gelatin immediately forms a spherical shape to reduce the interfacial free energy & traps dose inside, SGC falls through a cooling liquid, capsules collected washed & dried
what is the Rotary Die method of SGC encapsulation?gelatin fed over 2 die rolls in the form of 2 molten ribbons, as the 2 ribbons come together the API dispersed/dissolved in oily liquid is dosed in gap between, ribbons seal and formulation enclosed, SGCs automatically cut from ribbon, cooled and tumble dried
how does SGC formulation differ from HGC?much of the gelatin replaced by water, 40-50% gelatin, 20-30% plasticiser i.e. glycerol or sorbitol, 30-40% water preservatives and dye. API usually dissolved/disspersed in either oily non water miscable base (veg oil or waxes) or water miscable base (PEG 4000 with wetting agent)