Pre-Midterm Flashcards
8 advantages of Solid Dosage Forms
Unit dose
Cost of shipping
No breakage or leakage
Masking taste less difficult
More portable
Require less space per dose
Good physical and chemical stability
Elegant distinctive appearance which has a high patient acceptability
Disadvantages of a solid dosage form
Potential bioavailability problems
Potential irritant effect on GI mucosa
Occasional difficulty in formulation
Manufacturing can be more technical or
specialized
What are the Physical Properties of Solids
a) Particle size
b) Mixing powders
What are the Types of compounded powders
Bulk powders for internal use
Other bulk powders
Dissolution rate:
the rate at which the particle dissolves.
By increasing the surface area, one may increase the bioavailability for some poorly soluble drugs, because there is often a direct relationship between dissolution rate and bioavailability and drug absorption.
Suspendability
the ability of particle to remain undissolved but uniformly dispersed in a liquid vehicle.
Accuracy of dosage form
there must be uniform distribution of drug substance in a powder mixture or dosage form, and to ensure batch-to-batch uniformity.
Penetrability
the ability of particle to reach their intended location, e.g. to be inhaled deep into the respiratory tract particles should be 1-5 μm.
Non-grittiness
do not want solid particle in dermal products to feel “gritty”. Finer particles allow for a smoother texture and better appearance and flow. This is also important for oral products such as chewable tablets.
Chemical stability
refers to degradation reactions (e.g. oxidation and hydrolysis). Smaller particles have an increased surface area, leaving them more exposed and vulnerable to reactions with oxygen, water and light.
Flowability
effect on flow properties of powders and mixing of powders and granules. This is important in the manufacturing of tablets and capsules.
Compressibility
effect on adhesion and “sticking” together when compressing granules into tablets. This is important in the manufacturing of tablets and capsules.
the larger the mesh#
the smaller the particles
Monodisperse powders
powders containing particles of uniform size, RARE
Polydisperse
particle size varies a great deal
Comminution
Comminution is the mechanical process of reducing particle size of a solid substance to a finer state of subdivision.
Small-scale comminution
Most commonly involves the use of a mortar and pestle and is done by
the pharmacist or technician.
trituration
the process of grinding a drug in a mortar to reduce its particle size
levigation
the process of mixing a powder with a liquid or semi-solid vehicle (the levigating agent), in which the powder is insoluble, to form a smooth paste
pulverization by intervention
particle size reduction with the aid of an additional material, which can be later, removed
lSpatulation
blending powders with a spatula on a tile or paper
Advantages (of powders as a dosage form)
Flexibility in compounding.
Suitable for infants and young children who cannot swallow tablets or capsules.
Rapid onset of drug action because disintegration is not required.
Can be applied to many body cavities such as ears, nose, tooth socket, and throat.
Relatively good chemical stability.
Disadvantages of powders
Potential for misunderstanding of the correct method of
use that can lead to inaccurate dosing.
Undesirable for bitter or unpleasant tasting drugs
Dentifrices
dental cleaning powders, denture powders
What types of substances that do not dissolve gelatin may be encapsulated in capsules.
Dry powders, semi-solids and liquids
Water content of HGC shells?
13-16
Spot-welded
by means of a heated metal pin pressed against the cap, fusing it to the body.
Banded
colored molten gelatin is laid around the joint between the 2 capsule parts in a strip and dried
Most common capsule diluents are
Lactose
Microcrystalline cellulose
Starch
Most common capsule disintegrants
Pre-gelatinized starch
croscarmellose
sodium starch glycolate
Disintegrants
Disintegrants serve assist in the break off the powder
Mass/granules and help in distributing the drug through-out the stomach.
Lubricant and Glidant
Improves fluidity and flow of powders
Decreases sticking of powders to metal surfaces
Wetting Agents
Surface active agent such as
sodium lauryl sulfate
are often added to facilitate the wetting of the drug substance by the GI fluids, thus enhancing dissolution.
What are the components of a tablet?
Diluent, Binders, Disintegrants, colorants, coatings
Examples of diluents for tablets
Lactose
Dextrose
Starch
MCC
Mannitol
What happens if you have to little binder?
fragile tablets
What happens if you have too much binder?
Excessive hardness
Example of disintegrants
Corn Starch
Potential Problems with Sugar Coating
Many steps of this process involve tumbling – tablets must be hard enough to withstand it
Sugar coating pans must mix uniformly or coating goes on unevenly resulting in tablets of different sizes and weights
Most common tablet coating
Film Coating
What can aqueous tablet coating lead to?
Orange peel effect where the surface due ot failure of spray droplets
What is Enteric Coating?
Allows for disintegration in the intestine rather than the stomach.
WHat are the physical feautres of a tablet?
Appearance
Size
Shape
Organoleptic Properties
Friability test
Ability of tablet to withstand abrasion in packaging, shipping and handling; in other words, its tendency to crumble).
What is an acceptable amount of loss during the friability test? %
Usually acceptable value is <1% loss
Drug Content Uniformity
Two tests can be used to evaluate whether the amount of drug is uniform from one tablet to another one:
Weight Variation
Relies on tablet weight to assess the amount of drug in each unit
The greater the amount of drug, the more accurate the method is
Content Uniformity
May be applied in all cases (items listed under weight variation)
Assesses uniformity of content by assaying each dosage unit.
Disintegration
Tablets (or other solid dosage forms) must disintegrate within a specified time period
What is the most important test?
Dissolution
What is the Dissolution test?
dissolution test measures the amount of time required for a certain % of the drug substance to dissolve under specified conditions (which resemble physiological conditions).
What are Molded Tablets?
Prepared by molding rather than by compression
What are Molded tablets not appropriate for?
Not appropriate for potent drugs due to difficulties with content uniformity
limitations of chewable tablets?
Drug material is bitter and flavouring is important and often5 difficult.
What is Mannitol?
Adds sweetness and a cool tase
~50% of formulation in chewable tablets.
Effervescent Tablets
Large wafer-like tablets which dissolve rapidly in water
Tablet breakup is facilitated by the release of carbon dioxide (CO2) generated from sodium bicarbonate and citric or tartaric acid
Where are buccal tablets placed?
Side of cheek
What does gelatin do to a tablet?
Makes it soft hence usually a soft chewable
What does corn syrup do to a tablet?
Make it hard hence hard lozenge
What does polyethylene glycol do?
Make it soft so more likely a soft lozenge
Capping
the partial or complete separation of the top or bottom
crowns of a tablet from the main body of the tablet.
Lamination
the separation of a tablet into 2 or more distinct layers,
i.e. transverse cracking and separation of tablet.
Causes of Lamination / Capping
Air entrapment in light and fluffy powders
Excessive “fines”
Too little moisture in granulation
Weak granules or too weak a binder
Improper adjustment of machinery
Picking
the surface material from a tablet that is sticking and being removed from the tablet surface by a punch. Usually associated with letters such as “A”, “B”, “O” and “P”, etc from logos and lettering in the punch surface.
Sticking
tablet material adhering to the die wall.
Causes of Picking/Sticking
Inadequate lubrication (adhesive components may be present)
Insufficiently dried wet granulation
Poor finish on punch surfaces
What is Whiskering?
fine edge attached but not broken off tablet. End up with high friability values since “whiskers” are removed in friability testing.
Causes of Whiskering
Especially deep concave punches
Punches worn and in poor condition
Friability
It refers to the ability of the compressed tablet to withstand abrasion or crumbling in packaging, handling and shipping.
Causes of Poor Disintegration
Tablet hardness too high
Low amount of disintegrant. May require better disintegrant
Too much binder
Over lubrication causing “waterproofing”
Mottling
an unequal or uneven distribution of colour on or in a tablet.
Low Hardness
Low hardness can lead to rapid release of drug from dosage form or tablet will be too fragile for shipping and handling.
Dissolution
The transfer of molecules and ions from a solid phase into a solution
Factors affecting solubility
Molecular weight, volume.
Presence of functional groups and their position.
Acids or bases (pH dependent solubility – ionized form more soluble).
Increase temperature ___ solubility
decreases
Increasing pressure ___ solubility
Increases
Miscibility
expresses the mutual solubility of components in a liquid-liquid system (mixes without separating)
In an Endothermic solution Solubility ___ with increase temperature
increases increases
In an exothermic solution solubility ___ with increased temperature
decrease
Primary solvent for many organic compounds
◼ alcohol
◼ isopropyl alcohol
◼ glycerin
◼ propylene glycol
◼ polyethylene glycol 400
What is the most common solvent?
Alcohol
Advantages of semi-polar solvents?
◼ Better solubility for many compounds
◼ Can be used as co solvent
◼ Better stability for the drug:
◼ Hydrolysis
◼ Bacterial growth
◼ 70% is used as a skin antiseptic or for sterilizing work surfaces (BSC)
Limits for Alcohol in OTC products:
Children <6
Children 6-12
Adults
0.5
5
10
Denatured alcohol
Has additives (ketones or kerosene) to render it more poisonous and unfit for internal use
Absolute alcohol (100%)
Essentially water-free ethanol
Diluted Alcohol NF
prepared by diluting Alcohol USP with an equal volume of Purified Water USP
Rubbing Alcohol:
◼ Around 70% by volume.
◼ Effective antiseptic-disinfectant
◼ For external use only (dye can be added)
Miscible Solvents
a solute may be more soluble in a mixture of solvents than in one solvent = co-solvent effect
If there are two or more solvents and two or more solutes in a formulation,
each solute should be dissolved in the solvent in which it is most soluble before mixing with other liquids in the preparation.
Complexes are
loose molecular associations that can either increase/decrease solubility.
Solutions for oral administration often include additives WHY?
Storage stability, enhance solubility, taste etc.
What are the 4 primary tastes
Sweet, Sour, Bitter, Salty
What is the Flavouring techniques Physiological
anesthetize the taste buds/receptors
What is the Flavouring techniques Physical
◼ Prevent dissolution of drug (prevent it from coming in contact with taste buds)
What is the Flavouring techniques for Overshadowing
Addition of a flavour whose intensity is longer and stronger than the taste of the drug (e.g. Methyl salicylate)
What is the Flavouring techniques for Blending
add flavours which compliment the taste and modify the flavour
perception (e.g. Vanillin, benzaldehyde)
◼ sourtaste–blended with fruit flavours
◼ bitter taste – adding salty, sweet and sour flavour
Chemical
Drug can be complexed or a prodrug can be made
Used in drug product manufacturing
Other factors besides taste:
Aroma
Texture
Viscosity
2 categories of sweeteners
Natural sweeteners that include
sugars and polyols such as sucrose,
Artificial sweeteners
What are the sweeteners-Sugars
Sucrose
Lactose
Dextrose
What are the Natural Polyols? (Sugar free)
Sorbitol
Mannitol
Xylitol
Artificial sweeteners
Saccharin
Cyclamate
Aspartame
Sucralose
Stevia
What is the issue with Aspartame?
Aspartame degrades into diketopiperazine when
exposed to high temperatures (180C)
Intolerance in patients
PKU incidence 1 in 20 000
No colour is certified for use in the?
Eye
What concentration of dye colour do we usually use?
0.0005-0.001%
When should preservatives/antimicrobials not be used?
Formulation used immediately
No water is present
PH is less than 3 or greater then 9
Where are preservatives CI?
Neonates
Ophthalmics
Volumes greater than 30
What are the 2 aqueous solutions?
Syrups and Aromatic waters
What are the non-Aqueous Solutions?
Elixirs, Spirits, tinctures
What concentration of alcohol is usually in syrups?
up to 10%
What are the non medical ingredients in Syrups that we should know? (4)
Glycerin, Propylene glycol, sorbitol, sucralose
What % of sucrose should be in syrups before not having to add antimicrobrials
<80%
What is simple syrup?
Concentrated with sucrose and has self preservative properties
What is the alcohol content of a spirit?
62-85%
What is the alcohol concentration oin tinctures?
15-80%
What is the concentration of alcohol in elixirs?
3-44%
