Excipient list Flashcards
What types of bases are used in vaginal dosage forms?
Water soluble or water miscible
–> polyethylene glycol or glycerinated gelatin
What are the two types of action that an active ingredient could be used for in a suppository?
Local –> anti-fungal, astringent, anti-inflammation, hemorrhoids, anesthetics and antiseptics
Systemic –> antiemetic (N/V) and analgesic
What are the 3 drugs from Top 100 that can be used as an active analgesic ingredient in suppositiories?
Acetaminophen, aspirin, and morphine
What is an example of a preservative used in suppositories?
Parabens
What is an example of an antioxidant used in suppositories?
Butylated hydroxytoluene (BHT)
What are some examples of a plasticizer used in suppositories? (2)
- cetyl alcohol
- propylene glycol
What is the purpose of a plasticizer in suppositories?
reduces brittleness and increases flexibility
What are absorption enhancers used for in suppository formulation?
Surfactants to increase wetting and spreading, may increase permeability of the rectal membrane
What is an example of a viscosity enhancer used in suppositories?
Also called suspending agents; Silicon dioxide
What are some properties of an ideal suppository base?
- melt at body temperature or dissolve and disperse in the rectal fluids
- release drug readily/compatible with drugs
- stable on storage and when heated above its melting point
- non-absorbable
- non-toxic and non-irritant to rectal mucosa
- keeps shape when handled
What are the two classifications of suppository bases? Give two examples of each.
- Fatty/pleaginous/hydrophobic bases:
- cocoa butter
- synthetic/semi-synthetic - Hydrophilic/water soluble/water miscible bases:
- glycerinated gelatin
- polyethylene glycols (PEG)
What are some of the physical characteristics of Cocoa butter or Theobroma oil?
- yellowish-white solid with chocolate like odour
- mixture of triglyceryl esters of palmitic, stearic, oleic and other fatty acids (mostly unsaturated)
- softens at 30o and melts at 34-35o (B-form)
What are some of the advantages of cocoa butter/theobroma oil as a suppository base?
- melts readily on warming
- compatible with many ingredients
- non-irritating
What are some of the disadvantages of cocoa butter as a suppository base?
- polymorphism when heated above melting point
- adherence to mold
- should be refrigerated
- slow deterioration during storage
- poor water absorbing capacity
- leakage from body
How are semi-synthetic fatty bases (or hydrogenated vegetable oil bases) made?
hydrolyzing vegtable oil and re-esterfying the acids with glycerol
What is Fattibase a mixture of?
Palm, palm kernel, coconut oil, self-emulsifying glyceryl monostearate and polyoxyl sterate
What is the melting point range of Fattibase?
35.5-37o
What is Witepsol a mixture of?
triglycerides of saturated fatty acids (C12-C18) range
What is the melting point range of Witepsol?
33-350
What category of suppository bases do Fattibase and Witepsol fall into?
Semi-synthetic fatty bases
What are some advantages of semi-synthetic fatty bases?
- no polymorphism
- tolerance to oxidation
- rapid solidification
- better contraction
- improved drug release and bioavailability with presence of surfactants
What are some of the disadvantages of semi-sythetic fatty bases?
- some bases need to be stored in the fridge
- become brittle if cooled quickly (Witepsol)
- may have dehydrating effect because of the surfactants
What is the composition of glycerinated gelatin bases?
10% water
70% glycerin
20% gelatin
What are glycerinated gelatin bases frequently used for and why?
Vaginal suppositories → they have a laxative effect which is not compatible with rectal dosage forms
What are some of the advantages of glycerinated gelatin bases?
- slowly dissolves in mucous lining (makes it better for antiseptics than fatty bases because of slow dissolving ~30-40 minutes)
What are some of the disadvantages of glycerinated bases?
- osmotic laxative effect
- more difficult to prepare and handle
- dissolution time depends on the age of the base, content and quality of the gelatin
- hygroscopic → leads to irritation and dehydration of mucosa
- incompatible with protein precipitants like acids
Why were two forms of gelatin developed and what is the difference between types A and B?
Developed to use with either cationic or anionic antiseptics
→ type A = cationic
→ type B - anionic
How can you adjust the physical properties of PEG bases?
Varying the mixture of high and low molecular weight polymers
What is Polybase a mixture of?
PEGs and polysorbate 80 (surfactant)
What are some of the advantages of PEG bases?
- easier to prepare
- contracts significantly and does not stick to mold → makes it easier to remove
- no cool storage required
- does not leak from the body
- absorbs water well
- good solvent properties
- reliable, slow release of drug (30-50 minutes to dissolve)
What are some of the disadvantages of the PEG base?
- hygroscopic → should be moistened with water before insertion
- contract significantly on cooling → may form pits/holes
- incompatible with phenolic substances
- tannic acid
- aspirin
- benzocaine
- salicylic acid
What is the difference between group 1 and 2 excipients for tablets?
Group 1 → processing and compression characteristics of the tablet (diluents, binders, glidants and lubricants)
Group 2 → gives physical characteristics to the finished tablet (disintegrants, surfactants, colours, flavours, sweetening agents, polymers)
What is the purpose of diluents in tablet formulation?
Added to increase the bulk to make the tablet a practical size for compression
What role does lactose play in the formulation of a tablet? Are there different types for direct compression and wet granulation?
Lactose = diluent
For direct compression use anhydrous and spray dried lactose
For wet granulation use monohydrate grades
What role does microcrystalline cellulose play in tablet formulation?
Microcrystalline cellulose = diluent OR binder
Used in direct compression; 100 um
Used in granulations; 50 um
What does dicalcium phosphate dihydrate do in tablet formulation?
Dicalcium phosphate dihydrate = diluent
→ excellent flow properties and brittle
What role does calcium carbonate/sodium carbonate play in tablet formulation?
Diluent
→ brittle material
What role does starch play in the formulation of a tablet?
Starch = Diluent OR disintegrant OR binder
What role does dextrose, sucrose, mannitol or sorbitol play in the formulation of tablets?
Diluents OR filler and sweetener in effervescent or chewable tablets
What does a binder do in the formulation of tablets?
Imparts cohesive qualities to powdered material and to the tablet formulation
Ensures tablet remains intact after compression
What happens when you have too little or too much/too strong of the binder in tablet formulation?
Too much = inhibits disintegration
Too little = tablet falls apart
What are the two types of binders?
Solution binder → added as the granulation fluid (more effective and most common)
Dry binder → added before wet granulation or mixed with other ingredients before compaction
What are some examples of solution binders?
- starch mucilage (most common - 10-20% in aqueous solution)
- sucrose solution
- polyvinylpyrrolidone
- gelatin
- cellulose derivatives
What are some examples of dry binders?
- microcrystalline cellulose
- polyvinylpyrrolidone
- pre-gelatinized starch (easier to prepare than starch mucilage)
What does a lubricant do in tablet formulation?
Prevents adhesion of the tablet material to the surface of the dies and punches
Facilitates ejection of the tablets from the die cavity
What are some examples of insoluble lubricants used in tablet formulation?
- magnesium stearate (most common)
- calcium stearate
- stearic acid
- light mineral oil
What are some examples of soluble lubricants in tablet formulation?
- sodium benzoate
- PEG 4000 and 6000
- sodium lauryl sulfate (also used as a surfactant to help dissolution rate)
What are the most effective lubricants?
Hydrophobic lubricants
At what point in the formulation would you add in a lubricant?
LAST → after all of the other components have been thoroughly mixed
What does ‘bolting’ the lubricant mean?
Lubricant being finely divided by passing it through a 60-100 mesh onto the granulation
Are lubricants inert?
NO → they effect both dissolution and absorption
smaller concentrations of stearate increase dissolution and absorption
What does a glidant do in tablet formulation?
Improves flow characteristics of a powder mixture by reducing inter-particle friction
***you do not need a glidant if your powder has good flow
At what point in the formulation would you add in a glidant?
Always added in the dry state, just prior to compression (during lubrication step)
What are some examples of glidants in tablet formulation and what is the most common one?
- colloidal silicon dioxide (most common)
- talc
- calcium silicate
- magnesium carbonate
What does a disintegrant do in tablet formulation?
Added to a tablet to facilitate it’s breakup or disintegration after administration
What are the three major mechanisms of disintegrants in tablet formulation and what are some examples of each?
- Facilitated water uptake → facilitates transport of liquids into the pores of the tablet (starch, microcrystalline cellulose)
- Swelling on contact with water → also called super-disintegrants (sodium starch glycolate, croscarmellose sodium, crospovidone)
- Gas production in effervescent tablets → when in contact with water produces CO2 (citric acid, tartaric acid + sodium bicarbonate)
What are the most commonly used colouring agents?
Iron oxide pigments (red, yellow, black) and indigo carmine (FD&C) Blue 2
When should you add colour into the tablet formulation to get a more uniform colour?
during the coating step
What is the role of wetting and solubilizing agents in tablet formation and what are some examples?
Facilitates solubilization or water-insoluble drugs and wetting of hydrophobic tablets
→ SLS, docusate sodium, lecithin, poloaxamer, polysorbate 80
What is the purpose of sorbents in tablet formulation and what are some examples?
Absorbs oils or oil-drug solutions into a powder mixture during granulation and compaction
→ microcrystalline cellulose, fumed silica, magnesium carbonate, kaolin
What are the two types of gelatin used in hard capsule shells?
Type A → derived from pork skins by acid processing
Type B → derived from bones and animal skins by alkaline processing (takes longer as you have to decalcify the bones)
What are some of the advantages of gelatin hard capsule shells?
- strong flexible film
- consistent dissolution → soluble in water and GI fluids at body temperature
What are some disadvantages of gelatin hard capsule shells?
- cannot be used in vegetarian patients
- cross linking can happen and greatly slows dissolution
- mechanical stability is dependant on the water content
What ingredients are included in gelatin capsule shells?
- gelatin (20-30%)
- water
- colouring agents
- flavouring agents
- processing aids (<0.15% of SLS to help gelatin uniformly cover molds)
- preservatives → parabens
What are some advantages of hydroxypropyl methylcellulose (HPMC) hard shell capsules?
- plant-based; good for vegetarian patients
- immediate and modified release options available
- low moisture content → great physical stability
- consistent dissolution → no cross linking
What are some disadvantages of HPMC shell types?
- rough capsule surface; not as shiny (could also be considered an advantage because they’re easy to coat)
- harder to produce uniform colouring
What fillings are compatible with hard capsules?
- dry powders
- pellets
- granules
- tablets
- semi-solids
- non-aqueous liquids
What are soft gelatin capsules?
A liquid or semi-solid matrix inside a one-piece plasticized gelatin shell
What are the ingredients usually used in soft gel formulation and how much of the weight do they take up?
- gelatin (type B more common) → 40% of gel mass
- Water (solvent) → 30-40% wet gel mass, 8-16% after drying
- Plasticizers (glycerin, sorbitol, propylene glycol) → 20-30%
- preservative (parabens) → 0.1%
- colour and opacifier (TiO2) → qs
What are some alternative polymers that can be used in softgel shell formulation instead of gelatin?
Starch and carrageenam
polyvinyl alcohol (PVA)
What are the types of fill formulations for soft gel capsules?
- Hydrophilic liquids
- lipophilic liquid
- Self-emulsifying drug delivery systems (SEDDS)
- Self-micro emulsifying drug delivery system (SMEDDS)
- Self-nano emulsifying drug delivery system (SNEDDS)
What are some of the properties of hydrophilic liquid fill formulations in soft gel capsules?
- PEG 400 and 600 are commonly used
- also propylene glycol and glycerin
- ethanol and water incorporated below 5-10%
- problem with drug precipitation when contact with water in the GI tract
What are some of the properties of SEDDS/SMEDDS/SNEDDS fill formulations in soft gel capsules?
- oil phase and non-ionic surfactants mixture
- spontaneous emulsion formation in the GI fluid; stable for a longer time
- high surface area provided by the surfactant micelles containing solubilized oil and drug
What type of base makes up hard lozenges?
hard sugar candy base
What type of base is used for soft lozenges/pastilles
PEG base, sucrose, acacia base
What type of base is used in the formulation of chewable lozenges (gummies)?
glycerinated gelatin base
What was the first type of coating used for tablets and how long does it take?
Sugar coating in 1856
→ traditional process = 3-5 days
→ automated process = 1 day or less
What was sugar coating largely replaced by and why?
Film coating → cheaper, takes less time, gives ability to modify release
What does film coating involve?
Deposition of a thin, uniform polymer coating onto the surface of the tablets, capsules or multiparticulates/pellets
What are some polymers used in immediate-release coating?
- cellulose derivatives → hypromellose or MPMC, hydroxypropyl cellulose (HPC)
- Vinyl derivatives → polyvinyl alcohol (PVA)
- acrylic derivatives → methymethacrylate copolymers, methacrylic acid copolymers
What are some of the properties of polymers used in film coating?
- good solubility range and pH range
- good film strength, flexibility and adhesion
- compatible with film coating excipients
- stability under storage conditions
- absence of bad taste
- non-toxic
What are enteric coatings used for?
Protect the drug from the stomach acids and deliver it to the intestine
What effect does pH have on the polymers used in film coating?
Low pH → polymers remain unionized and insoluble
High pH → polymers readily ionize and dissolve (>pH 5)
What are some properties of extended-release coatings used in film coating?
- polymers are insoluble in water
- films are permeable to some extent
What are some examples of extended-release polymers for film coating?
Ethylcellulose
acrylic resins
polyvinyl acetate (PVA)
What are the two types of solvents used in film coating?
Organic → alcohols, ketones, chlorinated hydrocarbons, dichloromethane
Aqueous → water is most common
What are some of the disadvantages of organic solvents used in film coating?
- expensive; need efficient venting and plant optimization
- safety issues; flammable, toxic
What are some of the disadvantages of aqueous solvents?
- slow evaporation, longer drying time
- appearance of small amounts (picking) or larger amounts (peeling) of film fragments
- mottling (colour migration)
What is the purpose of a plasticizer in film coating?
Improves flexibility of the coatings, reduces risk of film cracking
What are some examples of plasticizers used in film coating?
Polyols: propylene glycol, glycerin, PEG
Organic esters: diethyl phthalate, dibutyl sebacate, triethyl citrate, tributyl citrate, triacetin
What do colourants do in film coating?
Improve product appearance and identification, improve coated product stability
What type of pigment is preferred for film coating and why?
Insoluble is preferred because:
- reduce permeability of the coating to moisture; improves product stability
- bulking agent; increases overall solid content in the coating dispersion without increasing viscosity
- less colour migration
- opacifying
What is the role of the anti-adherent in film coating and what are some examples?
Reduces stickiness of the film and prevents substrate agglomeration
→ talc, magnesium stearate, glyceryl monostearate, high MW PEGs
What is the role of surfactants in film coating and what are some examples?
Emulsifies water-insoluble plasticizers, improves tablet wettability, ensures rapid dissolution of the coating in the stomach
→ polysorbate 80, sorbitan monoleate, sodium dodecyl sulfate
