Capsules
materials used in gelatin production
-44% pig skin -28% bovine hides -27% bones -1% other
gelatin
-G is a water soluble protein -it is a thermo-reversible structure (neat and that's why we can make things bc it stiffens them and turns them into a solid at a lower temp) -solubility at temp greater than 45 degrees C -setting at temp less than 30 degrees C
other capsule materials
-HPMC capsules: hydroxypropyl methylcellulose -pullulan capsules: water-soluble polysaccharide derived by bacterial fermentation from corn -PVA capsule: cellulosic -starch capsule: made from potato starch -V Caps: cellulosic, Kosher and Halal certified
collagen
-a defined matrix -keeps our bones from bumping into each other -keeps our joints lubricated -triple helix often times -boring AA composition -can make collagen softer to do things or chill to fully set them -organized helix gives us structural rigidity that we are after
what is a capsule
-a solid oral dosage form consisting of a shell and a filling -the shell is composed of a single sealed enclosure, or two halves that fit together and which are sometimes sealed with a band -capsule shells may be made from gelatin, starch, or cellulose, or other suitable materials, may be soft or hard, and are filled with solid or liquid ingredients that can be poured or squeezed -capsule shells are a combination of gelatin, water, opacifier and a plasticiser such as glycerin or sorbitol (mixing these together in a heating format to get this)
two aerodynamic air vents
-allow air to escape from the cap -critical when operating high speed filling machines -pushing air down when putting cap on, so this keeps API from blowing back out
inner cap technology: product examples
-arthritis relief: nebulized ibuprofen (outer capsule) -chemotherapy: anti-emetic solution (outer capsule) -solid COX II inhibitor (inner capsule) -chemotherapy agent (inner capsule) -keeps cancer patients from having to take 6 different pills
other uses of capsules
-as a suppository dosage form: soft capsule, can have lubricant, designed to melt at 37 degrees celsius -single dose application for topical, ophthalmic, and rectal ointments designed to be broken
Advantage over tablets
-better masking of aroma and taste (don't need much coating) -easier to formulate (using premade container rather than press) -easier to manufacture (automation, but more parts) -easier to vary dosage -easier to combine APIs -easier to swallow (size well contained, smooth) -very suitable to blinded clinical trials -useful for extemporaneous compound by Pharmacist -easier but not cheaper
determining filler amount
-calculate the volume displaced by the capsule components to determine the correct filler amount -QS= quantity sufficient (means you take it to final volume that it can contain)
disadvantage of soft capsules
-can be costly to produce -drug and capsule interactions -microbes like gelatin (food source) -gelatin is sticky when damp -can not perform extemporaneous compounding
inner cap technology: delivery system examples
-capsular system delivering a liquid, enrobed tablet and crystalline filled capsule -capsular system delivering a lipophilic matrix and two synergistic compounds separated by two separate capsules -HPMC capsular system administering a solubilized compound, two coated tablets and crystalline filled capsule
hard gelatin capsules
-consists of a base or body and a shorter cap, which fits firmly over the base of the capsule -start going up in numbers as they get smaller -tops and bottoms are usually different sizes
agarose
-double helix -dual helix made of galactose and anagalactose monomers -in terms of stiffness and hardness, its just like collagen
tapered rim
-engages easily with the cap for problem-free closure -allows the top to fit on well -allows for machinery to fit on there to decrease tolerance of machinery
six elongated dimples
-for gripping -maintain precise round capsule diameter, improving filling machine performance
capsule filling
-hard gelatin capsules can be filled with a large variety of materials of different physicochemical properties
hard vs soft capsule
-in soft gelatin capsule the plasticizer and gelatin ratio is 0.8:1 -in hard gelatin capsule the plasticizer and gelatin ratio is 0.4:1 so it's stiffer
closure of hard gelatin capsules
-lock caps -gelatin bands -heating -moistening -warm gelatin coating
limitation in properties of materials for filling into capsules
-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 gelatin causing it to soften and distort) -the volume of the unit dose must not exceed the size of capsule available -can spend less time on tablet process -very limited in size because limited by container of vessel
soft gelatin capsules
-one piece hermetically sealed soft gelatin shell containing a liquid, suspension or semisolid -improved bioavailability due to the API being pre-dissolved (can get drug effect much quicker (pain meds) -very good for water insoluble drugs (oils)--good for dissolving (not water resistant, which is not good because external H2O can cause problems) -easiest to swallow solid oral dosage form
other capsule dosage forms
-tablet within a capsule -capsule within a capsule -delayed release capsule -sustained release capsule
two half capsules
-tapered rim -6 elongated dimples -two aerodynamic air vents -closely matched locking rings -rounded, hemispherical ends
inner cap technology
-the combination can consist of a high potency insoluble active in a lipid emulsion, sustained release tablet and a cocktail of two crystalline active materials -can create combination of release profiles -can deliver incompatible and compatible drugs using different physical phases -consists of a primary HPMC capsule containing an emulsion, pH coated tablet, crystalline filled HPMC capsule and a beadlet filled gelatin capsule
advantage of soft capsules
-very stable when kept dry -compatible with liquids, suspensions and pastes -water miscible, water-immiscible, volatile (easily evaporated at normal temps) and nonvolatile
determining capsule size
-volume does NOT equal mass -volume * density = mass -volume changes depending on the manufacturing process
cGMP requirements for capsules
-weight 200 mg -uniformity 100% -disintegration 5 min -dissolution cm/sec -stability multiple -moisture permeation color and mg -the end of every good manufacturing process is quality control -tablet in ideal form will have 0% water **thickness, hardness and friability are not on this list
filling possibility
can mix around types to get around extended release (ppl want pain release fast) -can mix powders and pellets to get around this -pellets: extended release -powders: immediate release
rounded, hemispherical ends
mechanically stronger and more resistant to deformation
closely-matched locking rings
provide full-circumference leak-free closure
manufacture of hard gelatin shells
stage 1: spraying (sealing fluid is sprayed onto joined between cap and body); capillary action draws fluid up between the cap and the body. suction removes excess fluid stage 2: warming (a gentle heat application completes melting and fusion); gentle heat melts the two layers, which fuse together to form an impervious seal stage 3: setting (capsules set and harden at room temp)
preparation of gelatin
take bone and grind up that bone (comminution), process it and cook it with acid for couple days. then neutralize acid and let it sit for a bit longer, remove lime, adjust pH, and wash it. STUDY THAT FLOW DIAGRAM
gelatin and plasticizers
the function of the plasticizer is to reduce or control the rigidity of the gelatin. in addition, the type of plasticizer is not the same between dosage forms. water is the primary plasticizer for hard capsules while glycerol is commonly used for soft capsules. Plasticizers promote plasticity which is important for both hard and soft capsules -they add to the quality of being easily shaped and molded -softness makes it useful -water is plasticizer
