Capsules: hard and soft shell 💊 Flashcards
1
Q
Differentiate the materials used in the preparation of hard-shell capsules
Explain the impact of powder properties on capsule formulation/behaviour
Explain the steps involved and factors affecting drug release from hard-shell capsules
Explain how to extemporaneously prepare capsules
Determine if capsules fit pharmacopoeial requirements
A
2
Q
what are capsules and the two types?
A
Capsules are unit dosage form and are mainly destined for oral administration.
hard shell and soft shell
3
Q
Describe the shape and parts of a hard-shell capsule.
A
- cylindrical
- cap (red, short)
- body (yellow, long)
4
Q
How are capsules generally prepared?
A
- content filled into body
- cap snapped securely into place to prevent content leaking
Modern capsule shell will have indentations in the cap (on the inside) and body (on the outside), so that the cap is secured in place.
5
Q
What are the advantages of hard-shell capsules?
A
- longer shelf-life
- simpler formulation compared to tablets
- convenient
- good absorption profile
- tampering relatively easy to detect
6
Q
What are the disadvantages of hard-shell capsules?
A
- can be difficult to swallow in some patients-large
- specialist equipment required to manufacture
- issues if to be filled w liquid
7
Q
What substance are hard-shell capsules typically made from and how is it produced?
A
gelatin: hydrolysis of a protein from connective tissue known as collagen. sources of collagen: animals (swine, bovine, fish)
8
Q
two types of gelatin and production and how long it takes?
A
Type A gelatine
acid hydrolysis (pH 1-3).
The process can take up to 10 days.
Type B gelatine
basic hydrolysis
process can take up to 3 months.
9
Q
What is a non-mammalian source of gelatine and what are its properties?
A
Fish gelatine
- no bovine spongiform encephalopathy disease (BSE)
- renewable sourcing (from skin and bones of fish)
- odourless and tasteless
10
Q
What two properties can be used to characterise gelatine?
A
- bloom strength
- viscosity
11
Q
What is bloom strength?
A
gives info on rigidity of gel.
the force (in grams) needed to depress the surface of a gelatine gel (6.67%w/w aged for 16-18mins at 10°C) by 4mm using a flat-bottomed plunger (diameter 12.7mm)”
12
Q
What is the typical bloom strength of hard-shell capsule gelatine?
A
230-275g
13
Q
How is the viscosity of gelatine measured (and at what concentration)?
A
using a U-tube viscometer, concentration 6.67%w/w
14
Q
What is the range of values of viscosity for hard-shell capsule gelatine?
A
3.3-4.7mPas
15
Q
What are the organoleptic properties of gelatine capsules?
A
tasteless, odourless, clear
16
Q
How do gelatine capsules behave in body-temperature water vs room temperature water?
A
body-temperature: dissolve readily
room temperature: swell and soften
17
Q
hard shell capsules have XX mechanical properties
A
have good mechanical properties
18
Q
What is the approximate moisture content of gelatine capsules? What does the water within the gelatine do?
A
- 13-16%
- water acts as a plasticizer, maintaining film flexibility
- important when making drugs susceptible to hydrolysis
19
Q
What drugs should have careful consideration before formulating with a gelatine shell?
A
those susceptible to hydrolysis due to the high moisture content
20
Q
How does a gelatine capsule’s moisture content change in high humidity? What are the consequences?
A
- the capsule absorbs water
- shell becomes softer and more malleable
21
Q
How does a gelatine capsule’s moisture content change in low humidity? What are the consequences?
A
- the capsule releases water
- shell becomes more brittle and prone to breakage
22
Q
What 2 powders are gelatine capsules not compatible with and why?
A
- deliquescent and hygroscopic
- the desiccant/excipient within the powder will absorb humidity
- this will make the capsule softer/more malleable
23
Q
What APIs are gelatine capsules not compatible with and why?
A
- APIs susceptible to hydrolysis
- API absorbs moisture from the shell, this can affect the integrity of both the shell and API
24
Q
What is cross-linking within gelatine capsules? What is the consequence?
A
- the irreversible formation of strong covalent bonds between individual gelatine chains
- low/incomplete dissolution
- delay in disintegration
25
What can cause gelatine capsule cross-linking?
- light
- oxidising agents
- aldehydes and ketones
- metal ions
- heat
- high/low humidity
- sugars
26
How can cross-linking of gelatine capsules be prevented?
adding a protease to the dissolution medium (as gelatine comes from the protein collagen, will help it be broken up)
- pepsin: mild to moderate cross-linking
- pancreatin: mild cross-linking
27
What are 4 categories of excipients found in the shell formulation other than gelatine?
- colouring agents
- opacifying agents
- processing aids
- preservatives (not common anymore)
28
What are two types of colouring agents?
- water-soluble dyes
| - water-insoluble pigments
29
What are colouring agents used for?
- used for identification purposes: branding
- can colour entire shell or be used to write
- must meet legal requirements of country
30
What are opacifying agents used for?
- makes capsule shell opaque
- can be used in clinical trials to hide contents
- can provide some protection to light
31
What are processing aids used for?
ensure a uniform filling in the mould when manufacturing shells e.g. surfactants like sodium lauryl sulfate
also added as wetting agent
32
Why are preservatives not used as much in hard-shell capsules anymore?
capsule not very likely to come into contact with contamination due to insufficient moisture
and too tightly bound to allow microbial growth
33
What is advantages about gelatine being produced from collagen?
collagen is a protein so is water soluble and will readily dissolve and disintegrate in the GIT
34
What are 3 alternative materials to gelatine?
- potato starch
- HPMC/hypromellose
- Pullulan
all sourced from plants, unlike gelatine
35
How are potato starch capsules sealed?
a hydro-alcoholic solution is applied on the inside of the cap before it's placed on top of the body
36
whats the moisture content of the 3 alternatives to gelatin in hard shell production
Potato starch: 12-14%. moist moisture tightly bound
HPMC: 2-6% low
Pullulan: 10-15%
37
Why can potato starch capsules be used for modified-release preparations?
these shells can be coated where the coating solution will have good adhesion
38
In what ways is potato starch similar to gelatine?
- similar dissolution profile
| - odourless, tasteless
39
HPMC stability and behaviour in high and low temps
good stability
HPMC gels at higher temperatures and stays soluble at lower temperatures and sometimes, the addition of a gelling agents is required for manufacture.
40
what does the lowest moisture content of HPMC mean compared to gelatin?
HPMC is less hygroscopic than gelatine
less sensitive to low environments
so there's a lower risk of moisture leaking from the capsule shell to the API
41
How do the incompatibility issues of HPMC compare to gelatine?
HPMC has less
42
What drugs is HPMC not a suitable capsule shell for?
drugs sensitive to oxidation
43
How can HPMC shells vary from 1 manufacturer to another?
- gelling agents can affect the dissolution/disintegration profile
- therefore different manufacturers will have different release profiles
44
What is pullulan made from? use?
plant souce, fermented from tapioca
can use for clear shell capsules
45
What is similar between pullulan and gelatine?
similar disintegration and dissolution profile
46
What drugs is pullulan suitable for?
those sensitive to oxidation as pullulan is a good barrier
47
What is an issue with pullulan capsules and what can be done to overcome this?
- can adhere to tongue, palate, oesophagus, throat
| - wetting agents can be added
48
most common capsule shell alternative to gelatin? (hard shell)
HPMC.
Moisture content: low as 2-6% for HPMC capsules. This can help inform capsule selection for drug susceptible to hydrolysis
Permeability to oxygen: lowest for pullulan. This will have an impact if formulating drugs that are susceptible to oxidation.
Opacity- this can have an impact if capsules are used in clinical trials
49
range of capule sizes and most useful in humans?
000 --> 5
biggest ---> smallest
0 to 4 used most
50
Capsule size and the volume they can accomodate
```
000: 1.37ml
00
0: 0.68ml
1:0.50ml
2
3
4:0.21ml
5:0.1ml
```
51
How do elongated capsule sizes compare to regular capsule sizes?
- can fill an extra 10%
- capsule is narrower so will fill less volume
000el: 1.02ml
00el: 0.78ml
52
What 2 things does the capsule size selection depend on?
- the formulation: capsule should accommodate enough powder required for a dose
- the patient: studies indicated preference for small, distinctive coloured capsules
53
What is an important consideration with extemporaneous capsule preparation and how is this overcome?
- availability of capsule shell size
| - it may be necessary to split doses into multiple doses and advise patient on how many to take
54
What steps (unit processes) are involved in powder formulation for encapsulation?
- particle size reduction
- mixing
- capsule-shell filling
- packaging of finished product
55
Why is particle size reduction required? before filling
to ensure homogenoous mixing and lower risk of demixing
56
How does the number of excipients of capsules compare to other dosage forms?
capsules have the least excipients compared to other dosage forms
57
What are the requirements for the powder filling of capsules?
- uniform filling
- good stability of final product, avoiding incompatibilities
- should comply with pharmacopoeial quality requirements
- powder should have good flow properties
- drug released and available to be absorbed within the expected timeframe
- adhesion should be avoided, but some cohesion may be useful for plug formation
58
What types of drug are easier to formulate as hard-shell capsules? Why?
- potent drugs
| - they may only take up <20% of the capsule volume
59
What will the flow properties of a potent drug hard-shell capsule be determined by? What will it affect?
- the type of diluent used
| - will also affect the plug-forming ability of the powder
60
What is a plug?
a lightly compressed powder used to fill the capsule
| Plugs are prepared at much lower compression forces (20-30 N) compared to the forces used in tablets (30 kN)
61
What types of drugs will occupy most of the capsule volume? What are the consequences?
- less potent APIs
| - excipients need to be active in low concentrations as they can only be used in limited amounts within the formulation
62
How are flow properties improved in capsules with the API as the majority of the content? (less potent drug)
- glidants - reduce friction w surfaces
| - lubricants - reduce adhesion
63
What other excipients are added to hard-shell capsules?
- disintegrants - increase release rate esp when using plug
| - surfactants - improve wetting of power esp hydrophobic ones with a high HLB
64
What are 2 ways capsules can be filled?
small batches: extemporaneous production
- individually
- using a manual capsule-filling machine
65
What are the main steps in manually producing capsules?
- caps separated from bodies
- bodies placed in filling machine
- bodies filled to capacity uniformly
- caps sealed onto body
- capsules cleaned off excess powder
66
What are 2 ways of sealing capsule?
- with a gelatine band
| - using hydro-alcoholic solution
67
how are manually filled capsules polished in order to remove traces of powder on the outside of the capsule in lab?
they can be shaken with NaCl
| wear gloves
68
What 2 steps should be taken to decide what capsule size to use for extemporaneous preparation?
- use a chart
| - calculate the quantities, despite not knowing the densities of the API
69
What does the capsule size chart tell us?
the fill weight that common chemicals occupy within a given capsule size
use these to estimate how much of your powder will fit in a capsule of a given size.
= rough idea of capsule size to use but final decision depends on powder properties (density and compressibility) and consider excipients
70
How would you use the chart to find the correct capsule size?
- choose a chemical similar to your powder substances
- determine the maximum capsule capacity
- pick a capsule size where at least 75% is occupied by the chemical
- use calculations to estimate how much powder will fit in a given size
- Don't forget excipients!
71
2. fill weight calulations. know density
calculate the fill weight of lactose and API needed to prepare 20 capsules with a dose of 100mg API per capsule. Size 0 capsules are available. API density = 0.9g/cm^3 and lactose density = 0.8g/cm^3 (all tapped densities)
1) first find the volume a size 0 capsule will hold = that's 0.67ml
2) next find the total volume required to fill 20 size 0 capsules: 0.67*20 = 13.4ml
3) find the total mass of API required if we're making 20 100mg capsules: 20*100 = 2000mg or 2g
4) find how much volume of the capsule this takes up by using the density: 2/0.9 = 2.22ml
5) subtract this from the total volume to find how much still needs to be filled: 13.4-2.22 = 11.18ml
6) use lactose's density to find how much weight in lactose you'll need: 11.18 x 0.8 = 8.944g.
72
How would you calculate the fill weight for lactose and API if you didn't have the densities?
- remember that for the previous example we needed to density to find the volume occupied by the API
- instead, find the total mass (2000mg) as before, and measure this amount in a graduated cylinder - this will tell you the approximate volume it will occupy
- then subtract that volume from the total volume occupied by the capsules i.e. (13.4-(volume occupied by 2000mg)
- this remaining volume is what lactose will occupy - measure that amount in a graduated cylinder
73
In a gelatine capsule shell, what will release depend on?
the dissolution of the gelatine shell exterior
disintegrate quick at body temperature
74
What part of the capsule splits first during dissolution?
the shoulders.
whereas the cap-body overlap takes longest to dissolve
75
What are the steps to the dissolution of a gelatine shell capsule?
- water will enter the shell and interact with powder
- the gelatine polymer will hydrate
- the gelatine polymer will begin to dissolve
- the first split will occur at the shoulder of either the cap or body
- the contents will begin to release before the shell has been dissolved
- the cap-body overlap is the last to dissolve due to the extra strength
76
What does the dissolution profile of a capsule depend on: the capsule shell or the powder contents? Why?
- the powder contents
| - not all of the shell needs to dissolve/disintegrate before the contents are released
77
what type of shell material capsules take longer to split
HPMC may take longer than gelatin
78
Drugs we use in capsule formulations are usually....
hydrophobic and poorly water soluble
79
What is the effect of adding a water-soluble diluent to a hydrophobic drug-containing capsule?
it will increase/improve the dissolution rate by providing water solubility and affinity. can use lactose: water soluble
dissolve in water, create space and easier for hydrophobic powder to break down.
drug in solution to be absorbed! this process helps
80
How do capsules with hydrophobic drug contents behave in contact with water? What does this impact the rate of?
- after shell dissolution, the contents will stay together as a tight compact mass
- this is due to the reduced affinity to water making it difficult to penetrate
- this will impact the drug release rate
81
How does lactose affect the drug-release rate of a hydrophobic drug?
- it will be incorporated into the tight compact mass of hydrophobic drug particles
- upon water contact, lactose will dissolve creating gaps
- these gaps will allow for the mass to be broken up easier and allows for quicker dissolution
82
A super hydrophilic drug will have a(n) soluble/insoluble diluent added to...
2 e.g.?
...control the dissolution rate
e.g. starch/microcystalline cellulose
83
what type of excipients to add to hydrophobic powder
soluble diluents (e.g. lactose) should be preferred
Surfactants can also be added to improve the wetting of a hydrophobic powder
84
Apart from the drug contents, what else within a capsule can affect the release profile?
- the excipients
| - lubricants/glidants can sometimes be hydrophobic which will impact the release profile
85
Apart from capsule contents, what else impacts the drug release?
the particle size of the powder
86
What particle size will have the quickest dissolution and hence absorption in the blood stream?
the smallest.
| highest peak and quickest on mean blood level/ time graph
87
What equation describes how particle size impacts dissolution?
the Noyes-Whitney equation
88
Why control release in capsules? 3
- protect contents from harsh environments
- improve tolerability
- control where the contents are released within the GI tract
89
How does the disintegration time compare between HPMC-shell capsules and gelatine-shell capsules?
HPMC-shells take slightly longer to disintegrate
90
Why are capsules more difficult to coat then tablets? What is done instead?
- capsules are less dense than tablets
| - powder is granulated, then granules are coated and encapsulated
91
When formulating capsules for controlled release, what 3 aspects of the GI tract can we exploit?
- pH
- transit time
- enzymatic profile/ microbiome
92
How do enteric coatings work?
- contain polymers that are active at higher pH values
| - therefore contents won't dissolve until the reach the small intestine (duodenum) where the pH increases slightly (6-7)
93
How does colon-specific release work?
- coating contains chemical bonds/specific carbs that can only be degraded by bacteria in colon as only found there
94
What is the beneficial environment of the colon and how does this help colon-specific release?
- lower proteolytic activity: improved drug stability
- allows for macromolecule drugs such as proteins to survive there with greater stability. otherwise degraded in small intestine
95
how are capsules with liquid or semi-solid filling are filled by...
by weight or volume
96
What are 4 ways to prevent liquid/semi-solid filling leakage from a capsule?
- avoid aqueous fillings as they can affect shell integrity
- inside of the cap can be sealed with hydroalcoholic solution
- a gelatine seal: belt can be placed around the cap and body
- a suitable base should be used
97
What should a suitable base for liquid/semi-solid filled capsules ensure?
that the capsule contents are solid at room temperature and liquid at body temperature
98
What are 4 categories of excipients used for semi-solid/liquid-filled hard-shell capsules?
- long-chain triglycerides
- medium-chain triglycerides
- solubilising agents/emulsifying agents/surfactants/absorption enhancers
- cosolvents
99
How should co-solvents be added as an excipient to hard-shell liquid/semi-solid filled capsules?
- cannot be added alone, and only in small concentrations
| - must be mixed with compatible excipients to be added in low concentrations
100
what is over-encapsulation and why is it done?
- filling a tablet within a capsule
- filling a capsule within a capsule (should have no incompatibility issues)
done to mask the contents inside a capsule e.g. in clinical trials
101
In what states could the contents to over-encapsulate be?
- whole or crushed tablet(s)
| - whole of an emptied capsule
102
When over-encapsulating the whole of an emptied capsule, what should be considered?
the capsule size - choose the one with the least impact on the biopharmaceutical properties
103
What are 3 formulation considerations with over-encapsulation?
- needs to be the right colour
- should be securely locked: tampering
- backfill with appropriate diluent in empty space
104
What are the biopharmaceutical considerations of over-encapsulation? (i.e. what should be unaffected?)
- unaltered dissolution
- unaltered bioavailability- legal challenges. not best conditions during clinical trial etc.
need right shell material and diluent in capsule. dont want ot over encapsulate as amount dissolved reaches max much quicker
105
What are the two packaging options for capsules?
- blister packs: opaque for protection
- glass/plastic bottle w child-resistant cap +/- dessicant capsule to absorb moisture to prevent moisture-induced degradation
106
pharmacopoeial requirements of hard--shell cpasules:
| What tests must capsules comply with?
- uniformity of dosage form: if the API is <2mg or fills <2% of the capsule contents
- disintegration
- dissolution: similar to tabs
107
What are the reasons for failing a uniformity test? (causes of under-filled capsules)
- loose powder plug- dose lodd
- electrostatically charged pellets- incomplete transfer
- cracks/holes in the dosage form
- poor powder flow
- variation in powder size/presence of large agglomerates
- weak dosator/tampering head spring
- overfilled capsule body
108
Under what conditions is the disintegration test performed?
water for 30 minutes
- with/out 0.1M HCl
- with/out enzymes
109
What capsule-shell material is the disintegration test valid for?
gelatine - HPMC may take slightly longer to start disintegrating
110
affect of adding too much magnesium stearate
lubricant: can increase hydrophobicity of a powder and slow release from capsule
111
how to improve dissolution rate of encapsulated hydrophobic powder?
add soluble diluent and
| high HLB surfactant
112
what can gelatin capsules not be filled with?
aqueous solutions: affect integrity of capule shell
113
what 2 things must over encapsulation not affect?
dissolution rate and bioavailability
114
Discuss the advantages and disadvantages of soft-shell capsules
Describe the main similarities and differences between hard-shell and soft-shell capsules
Discuss the formulation of soft-shell capsules and parameters affecting drug release and absorption
115
what are soft shell capsules?
soft shell/ softgel/ gelcaps = one piece hermetically (airtight) sealed capsules.
116
how is the shell of hard shell and soft shell capsules similar?
the shell is commonly made of gelatin, water and a plasticizer.
117
what is the appearance of softshell capsules like?
transparent/opaque with colouring and flavouring agents sometimes added
118
2 reasons why capsules may be coated?
to delay release or prevent release in the stomach
119
what should the water content be like in both hard and soft shell caps?
water content should be insufficient to allow microbial growth and preservatives are not normally added to the shell.
120
Soft-shell capsules are used to encapsulate what? (2)
Liquids (non-aqueous)
Semi-solids
usually oval shape
121
advantages of softgel caps (7)
- improved absorption = Increases bioavailability
- Easy to swallow
- Acceptable to patients
- Good organoleptic properties
- Avoids issues linked to handling powders
- Liquid flow easier to predict and control
- Improved stability
122
2 disadvantages of softgel caps?
expensive manufacturing process
| specialised manufacture equipment required
123
what type of gelatin is commonly used for softshell caps?
type B but both are suitable
124
softgel capsules use gelatins with a bloom strength of ?
Gelatins with Bloom strengths of ca. 150 g
up to 250g can be used for stronger shells but more expensive
125
role of plasticizers added to softgel caps shells?
Plasticizers (15-30 wt%) are added to make the shell flexible and elastic.
126
Common plasticizers added to softgel caps (5)
- glycerol (glycerin)
- sorbitol, maltitol, mannitol
- propylene glycol
- low MW polyethylene glycol
- mixtures of any of the above
127
in addition to having an affect on properties of the softgel shell (flexibility and elasticity), what else is affected? (3)by plastisicers
disintegration
dissolution
stability
128
what must be avoided regarding addition of a plasticizer?
incompatibility issues- plasticizer shouldnt leach from shell and combine with capsule contents
129
what will the soft shell's permeability to oxygen depend on? (protection against oxygen diffusion)
thickness of shell
| composition of shell-plasticizer and moisture content
130
what should be considered if the softgel capsules are to contoain ingredients suceptible to oxidation?
keep plasticizer conc low
store caps in cool,dry place
131
how will the moisture content of softshells have impact in
a) high humidity
b) low humidity environments?
a) becomes soft and sticky
| b) becomes hard and brittle
132
what makes softgel capsules suitable for encapsulation of drugs that are sensitive to hydrolysis
low moisture content.
| especially if the drug is dissolved or dispersed in an oily vehicle.
133
What are the 4 main types of softgel capsules available?
- capsules to be swallowed whole
- chewable caps
- suckable caps
- meltable caps
134
where will disintegration occur for capsules to be swallowed whole with water?
expected in stomach
135
why are some capsules chewable?
chewed to trigger drug release
the drug may be added to the shell
organoleptic properties will be important!
136
how are suckable capsules different in terms of content?
capsule shell contains the medicament
the inside of the capsule is either empty or contains a suitable liquid
organoleptic properties will be important!
137
what are meltable capsules often used for?
these include softgel capsules used as pessaries or suppositories
138
fill formulation
| Softgel capsules may be filled with: (3)
Solutions
Suspensions
Emulsions
but, consider incompatibilities i.e. not all liquids/semi-solids are suitable capsule fillings.
139
what 7 types/properties of materials are generally incompatible for softgel caps?
- v high solid content
- high water content
- very high/low pH
- lots of hygroscopic ingredients
- high concs of salts
- high concs of solvents e.g. ethanol
- high viscosity e.g. molasses
140
what may the 7 incompatibility materials for softgel caps affect?
stability/ integrity of the capsule shell, uniformity of filling (e.g. highly viscous liquids may not flow as easily and may cause issues during the filling process).
141
4 Formulation considerations for softgel capsule filling
- drug solubility in chosen vehicle
- how quick content disperse in GIT
- possible compatibliity issues with shell
- if can optimise drug absorption and bioavailability. through careful selection of the type of filling and excipients
142
name the 3 ways lipophilic/lipidic liquid fill formulations can be prepared
using:
- free fatty acids
- fatty acid esters derivatives of hydrophilic compounds
- triglycerides (e.g. medium or long chain)
143
preparation of a simple lipidic formulation
by solubilising/ suspending drug in a triglyceride (digestible oil or medium chain triglyceride- emulsions SoM1).
144
Lipophilic fill formulations may be suitable for.. (2)
```
potent drugs and/or
lipophilic drugs (log P >4)
```
145
what will the process and route of absorption vary depending on?
softgel caps-lipophilic fill formulations
depending on the type of oil used.
| digestible vs non-digestible oils vs medium-chain triglycerides
146
what will be used as an alternative when some drugs (even poorly water soluble ones) will not be soluble in long chain triglycerides?
medium-chain triglycerides may be used as an alternative OR free fatty acids may be added to the preparation.
147
softgel caps- why must you take care if the drug is in suspension?
examples?
to ensure that the suspension is homogenous, to ensure uniformity of content.
Examples: vitamin D, vitamin E, hormones
148
what are pre-concentrates and when may they be used?
self-emulsifying systems.
- included in lipid formulations of softgel caps.
- capsule filled with oil phase (contain oily vehicle, drug, stabilisers/surfactants/co-solvents).
149
Advantages of using preconcentrates?
- Improved drug solubility
- High surface area of the resulting micro- or nanoemulsion
rapid diffusion out of the oil phase into the intestinal fluids
- Improved pharmacokinetics
Example: cyclosporine
150
with preconcentrates, where is the final emulsion formed?
| benefit of this?
The final emulsions will be formed in situ in the intestines, once the capsules contents are released and mix with the aqueous fluids in the small-intestine.
= Improved drug solubility
151
give 3 possible fill formulations for softgel caps?
lipophilic fill forms
preconcentrates
hydrophilic liquids
152
softgel caps: fill formulation III.
what are hydrophilc liquids?
Suitable polar, non-aqueous vehicles should have a molecular weight large enough to allow the preparation of a solution or suspension.
e.g. Poly(ethylene glycol) 400 Da.
153
why is viscosity of Hydrophilic liquids important?
it will affect liquid flow and how easy it will be to fill the capsules
154
ideal properties of the Hydrophilic liquids used in softgel caps?
- suitable viscosity
- low MW solvents (e.g. ethanol) used at low concs only (<10%)
- avoid highly hygroscopic solvents
155
for hydrophilic liquids for softgel cap fill form, why should solvents be low MW and used at low concs?
Lower molecular weight solvents (e.g. ethanol) should be used at low concentrations (<10%) only, to avoid destabilising the gelatin shell.
156
how is content released for hard and soft shell caps?
the capsule shell will need to dissolve, at least partly, to allow its contents to be released.
157
what effect will cross-linking have on softgel capsules?
Crosslinking will affect dissolution/disintegration of the shell.
158
what 4 things affect dissolution rate of capsule content? (softgel)
- polymorph
- particle size and or size distribution
- crystalline state of a drug formulated as a suspension
- solubility of drug solubilised with help of hydrophilic solvent(s) or co-solvent(s)
159
how will particle size and/or size distribution affect dissolution rate of softshell capsule content?
for example due to Ostwald ripening in suspensions or emulsions
160
how will solubility of a drug solubilised with the help of hydrophilic solvent(s) or co-solvent(s) affect dissolution rate of softshell capsule content?
upon release the solvent(s)/co-solvent(s) will mix easily with aqueous fluids (in GIT), potentially triggering the precipitation of the drug
sometimes triggered by migration of water from the shell into the capsule contents
161
quality assessment of softgel caps during manufacturing process? (4)
Thickness of the gelatin film
Sealing of the capsules (absence of leaks)
Filling weight and shell weight
Moisture content and hardness after drying
162
quality assessment of softgel caps after manufacturing process? (3)
Softgel capsules will be assessed against pharmacopoeial criteria. Tests can assess:
uniformity of content
dissolution
disintegration
163
can softgel caps be used easily to perform a blinded clinical trial?
no cant open as with hard shell and add things. make new form, wouldnt have same properties.
164
how can lipidic filling formulation help improve bioavailability of a drug?
as with emulsion: sometimes have surfactants. --. solubilisers.
helps if have lipid phase
suscept to hydrolysis-degraded
by water
lipid: solubiliised in gut- affect bioavailability
165
disintegration test: What may have caused the capsules to fail to disintegrate in water and HCl, but not in the artificial gastric juice?
Cross linking of capsules = Low/incomplete dissolution = delay in disintegration
Enzymes can degrade proteins in GI tract- protease medium
- Pepsin degrades proteins therefore will degrade capsule during test.
Dilution so final conc not 1M (too high for physio. Condition)
