Exam 2 Flashcards
if a drug is formulated in a solution, suspension, and a tablet, which would have the best chemical stability?
tablet, less degradation of drug so least reactive
optimize the absorption rate of drug, increase the ease of administration by the patient, control the rate and site of drug absorption, mask the taste of therapeutic agent, improve chemical stability of drug
solid dosage forms designed to do all these things
increased stability (solid dosage forms have longest shelf life), ease of packaging/storage/dispensing, convenience and accurate dosing, little to no taste/smell of drug
advantages of solid dosage forms
solubility (drug must dissolve from solid dosage form), not suitable for some patients (pediatric/geriatric, patients have difficulty swallowing solid dosage forms - dysphagia), solid dosage forms not suitable for some routes of administration (IV, transdermal, ophthalmic, otic), some drugs lose their activity in solid form (therapeutic proteins, several biological products)
limitations of solid dosage forms
evaluate the impact of physiochemical characteristics of the drug (API) and excipients (solubility, dissolution rate, permeability, drug-excipient compatibility, stability), suitability and therapeutic activity of final drug product (quality, stability, marketability, patient acceptance, cost)
performulation studies
drug particles in some solid products are often micronized, this process increases….
dissolution rate of the drug (decrease the particle size)
purity (efficacy and safety), organoleptic properties (color, odor, taste), presence of polymorphs (crystal forms), surface properties (wettability), particle size and size distribution (monodisperse - uniform particle size vs polydisperse - different particle sizes)
solid-state properties
which has faster dissolution rate, higher solubility, but lower stability?(amorphous or crystalline)
amorphous structures
what is the function of a wetting agent in solid dosage forms?
increase contact between drug particles and liquid
what is used to measure the wetting of a substance by a liquid?
contact angle, lower angle number greater contact
a hygroscopic drug is one that…
adsorbs moisture from the environment
will take in moisture from the air until it gets saturated, want a drug that will not be this at low relative humidity, also need to take into consideration the amount of water being taken up (% weight change)
hygroscopicity
stability issues, physical changes, dosing accuracy, microbial growth, packaging challenges
problems due to hygroscopicity
methods to prevent problems due to hygroscopicity
moisture-resistant excipients, incorporate desiccants or moisture barriers, appropriate packaging materials, implement appropriate storage and handling practice
particles are measured in ___________ but this can be a challenge with irregular particles, use __________
diameter, equivalent sphere
examples of physical stability problems
capsules stick to each other, solvent from a solution evaporates, tablet dissolves slower than its specifications
excipients for solid dosage forms
diluents, binders, disintegrants, lubricants, glidants, opacifiers
a diluent is added to solid dosage formulations to…
act as a filler
glidants/lubricants are added in the manufacture of solid dosage forms to…..
reduce friction among particles
some excipients can perform more than one function, pre-processed and co-processed excipients, provide multiple functionalities to the formulation
multifunctional excipients
mannitol-calcium silicate co-processed excipient
chewable properties, flowability, compressibility
simple and convenient to use (solid unit dosage form), quick and safely manufactured into convenient doses for dose accuracy, carried in portable packages (improving compliance), can disguise unpleasant tastes with film coating, easily identified by markings, shape, and color for safety
tablet features
not all drugs suitable for oral use, some drugs deactivated by the liver (first pass metabolism), may not be suitable for emergencies (slow onset of action, need for patient cooperation), not suitable for patients that can’t swallow, some drugs poorly absorbed by GI tract, pill-cheeking
drawbacks to tablets
may affect drug product performance, makes powder blend more compact and affects tablet hardness
compression
disintegrate slowly, results in slower rate of dissolution, reduces rate of systemic drug absorption, affecting the clinical response
excessive compression may cause tablets to do these things
segregation of drugs from excipients (different particle sizes, density), friction between particles and between particles and equipment (clumping, sticking to equipment, poor flow)
problems with powders
dust reduction (reduces fine particles), improved flowability (spherical shape, less contact surface), particle size and uniformity control (monodispersity), compaction enhancement (binders), improve dissolution profiles (hydrophilic excipients), increased bulk density (compact, dense)
reasons for granulation
spraying, moistening, solidifying, finished agglomerate, HPC, MCC, PVP, starch, gelatin, sucrose, polyethylene glycol, drying with hot air
wet granulation
to determine whether tablets or capsules disintegrate within the prescribed time, quality-assurance measure, USP sets standards for this
disintegration test
control the rate and duration of drug release, target drug release to certain regions of the GI tract (small intestine or colon), plasticizers are added to render the coating flexible
film-coating tablets
mask taste, odor, color of drugs/excipients, provide a smooth finish for easy swallowing, make the tablet physically stronger, protect from moisture, oxygen, light, protect form toxicity due to contact with drug, provide identification, brand recognition, facilitate printing, enable controlled/delayed release
reasons for coating tablets
orange peel effect (roughness), blistering and film cracking, sticking (tablets stick together), bridging (coating bridges across logo), chipping (edge of tablet chips), color variation, tablet breakage, most of these are manufacturing issues but bad storage conditions can lead to these
tablet coating defects
required strength unavailable, fractional doses in flexible, increasing, decreasing dosage regimen (dose titration, as needed dosing), ease of swallowing, cost
why tablet split
dose uniformity (does the tablet split exactly into two equal parts?), do not crush list (is it proper to split a tablet not scored by the manufacturer?), how much of the tablet crumbles into fragments?, how easy is the process of splitting for elderly or disabled patients?
tablet splitting
crumbling, uneven sizes, waste, lack of dexterity, confusion about dose, forgetting to split
concerns with splitting scored tablets
dose dumping of controlled release products, destroy enteric coating, poorer stability, bitter taste, unwanted increase in dissolution rate, danger of exposure to the drug, patient’s counseling
dangers of splitting unscored tablets
coated with a polymer that does not dissolve under acidic conditions (stomach) but does dissolve under the more alkaline conditions of the small intestine (pH greater than 4), protection against possible drug degradation, reducing or preventing irritation of gastric mucosa
enteric coated tablets
separation of drugs into separate layers that may be incompatible when formulated as a single layer, conventional tablet, delivery of therapeutic agents at different rates or to different sites within GI tract
multilayer tablets
reaction between weak acid and bicarbonate produces carbon dioxide, helps mask taste, provide faster dissolution, allow administration of a large dose
effervescent tablets
tablets are chewed before swallowing, suitable for patients who have difficulty swallowing conventional tablets (pediatric, some adults), large size tablets (antacid formulations)
chewable tablets
rapid disintegration in the mouth, no need for water, improve adherence, 3D printed tabs, lyophilized (freeze dried tablets), loosely compressed, molded tablets
orally disintegrating tablets (ODT)
tablets administered under the tongue, small and flat tablet, suitable for conditions like angina, or migraine
sublingual tablets
tablet or film in the cheek or upper gum
buccal
patient measures out individual doses, limited to relatively non-potent drugs like laxatives, antacids, dietary supplements
bulk powders/granules
single doses in individual containers
divided powders/granules
- patients who cannot swallow
- longer shelf-life (more stable)
- convenient for dispensing drugs with a high dose
- medicaments have faster dissolution rate than tablets/capsules (drug release from powders/granules will be faster than from the corresponding tablets/capsules
- easy to formulate (compounding)
why powders/granules as dosage forms
less convenient for the patient to carry/administer, masking of unpleasant tastes may be problematic, bulk powders/granules not suitable for administration of potent drugs, not suitable for drugs that are inactivated in stomach, cause damage to stomach, sustained or controlled drug delivery
limitations of powders/granules
the particle size distribution of a powder is determined by…..
analytical sieving (USP)
to prevent segregation of ingredients in powder mix for dose uniformity, improve flow properties of mix (ease of dosing, reduce the loss of drug in packaging), improve compaction characteristics of mix (packaging), reduce dust (easier handling)
reasons for granulation
protects against light, air, moisture (improve chemical stability of API), multi-compositions (various release profiles like immediate and sustained release beads, chemically incompatible drugs physically separated), good flowability, mask taste and smell
benefits of particle coating
diluent/filler, glidant, lubricant, coloring and flavoring agents
excipients in powders/granules
solid dosage forms in which the API and excipients are enclosed within a soluble container/shell, shell may be composed of body and cap or single piece, shells usually made from gelatin but can be made from vegetable products, most designed for oral administration
capsules USP definition
hard shell (powder/powder-like contents), soft shell (oils/oily semisolid formulations), modified-release (delayed or extended release)
types of capsules
dipping, spinning, drying, stripping, trimming/cutting, joining
steps in production of hard gelatin capsule shells
- gelatin: type A and B gelatin
- water: 12-16%, functions as plasticizer (additional plasticizers can be added if needed)
- colorants, opacifying agents, wetting agents, and preservatives if needed
composition of empty hard gelatin capsule shells
what will hygroscopic materials do to capsule shells?
may dry out the capsule shell and cause it to become brittle
what will efflorescent materials do to capsule shells?
soften the capsules (take up water)
- rectification: placing empty gelatin capsules with bodies facing downward
- separation: of caps from bodies
- dosing: of fill material, the body is filled with formulation, dosing-disc machine/dosator machine
- replacement of caps: and closing capsule shells
- ejection: of filled capsules
capsule filling basic steps
spraying, warming, setting
fusion-sealing process of capsule sealing which prevents leaks and is tamper-proof/evident
oral softgels, chewable softgels, enteric softgels
types of soft gelatin capsules
test to measure the strength of a gel/gelatin, determines the weight in grams needed by a specified plunger to depress the surface of the gel 4 mm without breaking it at a specified temperature
bloom strength
high bloom strength gelatin is used in manufacturing of…..
hard shell capsules
shells of soft gelatin capsules may be made elastic/plastic by the addition of….
sorbitol (plasticizer)
- gelatin
- water (4-10%)
- plasticizer
- preservatives
- coloring and opacifying agents
- flavorings and sweeteners
composition of soft gelatin capsule shells
hygroscopic, volatile, acidic, aldehyde materials
can’t use these in filling softgels
