Prelims Flashcards
The general area of study concerned with the formulation, manufacture, stability and effectiveness of pharmaceutical dosage forms.
PHARMACEUTICS
This study deals with different dosage form designs which converts a drug into a medicine
PHARMACEUTICS
DRUG DELIVERY SYSTEMS
- The means of administering drugs to the body in safe, efficient, effective, reproducible and convenient manner
- allows for precise dosing
- In all cases, the goal of a drug delivery system is to get the right dosage to the right place
the group of atoms in the molecule of a drug
responsible for the drug’s action
pharmacophore
the ability of drug to bind to its biological target
Drug affinity
Drug should bind to specific receptor site on the cell
Selectivity
atmospheric oxygen or humidity
Coated tablets and sealed ampule
influence of gastric acid after oral administration
Enteric coated tablet
provide liquid preparation of substance that are either insoluble or unstable in the desired vehicle
Suspension
conceal the bitter, salty, offensive taste or odor of a drug substance
Coated tablet, capsules, flavored syrups
provide liquid dosage forms of substances soluble in the desired vehicle
Solution
provide rate-controlled drug action to decrease the frequency of drug administration
Sustained release tablets, capsules
provide optimal drug action from topical administration site
Ointments, creams, transdermal patches, ear and nasal preparations
insert a drug into one of the body’s orifices
Suppositories
place a drug directly into the blood stream or into body tissue
parental injection
provide optimal drug action through inhalation therapy especially to asthmatic patients
Inhalations, aerosols
Liquid Medicinal Agents: 2 approaches
- Liquid substances are sealed in a soft gelatin capsule
2. Liquid substances are developed into a salt form to convert into a solid such that it is chemically modified.
Example of liquids medicinal agent convert to solid
Arecoline and Scopolamine turns to hydrobromide form as solids
most preferred by researchers medicinal agents
Solid Medicinal Agents
following advantages of Solid Medicinal Agents
Stability, Ease of handling, and could be made into tablet and capsule
most encountered destructive processes in drug formulation are
hydrolysis and Oxidation
process in which drug molecule interact
with water molecules to yield breakdown products of different chemical constitution
HYDROLYSIS
In case of liquid formulation how can you protect it from hydrolysis?
the use of anhydrous vegetable oils as vehicle will also stabilize the formulation
Substituting liquids (hydrolysis)
glycerin, propylene glycol and alcohol for water
destructive process occurring in pharmaceutical. involves the change in the number of electrons from an atom or molecule
OXIDATION
taste of Low molecular weight substance
salty
higher molecular salts
bitter except some lead salts
increase the sweetness of the compound
organic compounds, an increase in the number of hydroxyl group (OH-)
nitrogen containing compounds are
extremely bitter like plant alkaloids
certain ether nitrogen containing compounds are extremely sweet like
saccharin
approved color additives are classified into 3 groups
FD & C dyes
D & C dyes
External D & C dyes
mixtures of finely divided drugs and/or chemicals used externally or internally in dry form
powders (pulvis)
process of grinding a powder in a mortar and pestle to reduce its particle size
TRITURATION
process of reducing particle size by first forming a paste of the solid with a minimum amount of a levigating agent and then triturating the paste in a mortar or on slab with a spatula
LEVIGATION
Is the reduction of particle size with the aid of a second agent which can be readily removed from the pulverized product
PULVERIZATION BY INTERVENTION
PARTICLE SIZE REDUCTION (COMMINUTION)
TRITURATION
LEVIGATION
PULVERIZATION BY INTERVENTION
method by which small amount of powders may be blended by a spatula on a sheet of paper or pill till.
SPATULATION
May be employed both to comminute and to mix powder using mortar preferably with a rough inner surface.
TRITURATION
small amount of potent substance is to be mixed with a large amount of diluent a general method
“geometric dilution”
process of mixing by passing the powder through sifters. Not generally acceptable for potent drugs
SIFTING
process of mixing powders by placing in large containers or powder blenders the rotates by tumbling motion
TUMBLING BY MECHANICAL MIXING
involves the pressing of mixed powders into an object to be reground into a precise powder
DRY GRANULATION
DRY GRANULATION also called
slugging or roller compaction
used to improve flow, reduce segregation,
enhance drying, and limit wide particle size distribution
Milling equipment
an efficient and versatile blending machine for
mixing and lubrication process of dry powders homogeneously
“V” BLENDER
volatization when incorporated may be prevented or
retarded by use of
heat-sealed plastic bags or by double wrapping with a waxed or glassine paper inside a bond paper
absorb the moisture from the atmosphere
Hygroscopic
absorb the moisture from the atmosphere and convert it into solution
Deliquescent
when two or more low melting substances are mixed together they liquefy due to formation of new compund
eutectic mixture
Are products which are completely soluble and are intended to be dissolved in water prior to use as antiseptic or cleansing agent for a body cavity
DOUCHE POWDERS
Form of bulk powder, generally containing flavors, soap or detergent, mild abrasive, & an polishing agent
DENTIFRICES
dilution of potent powdered drugs prepared by intimately mixing them with a suitable diluent in a definite proportion by weight
TRITURATION
Are non-toxic preparations for local application and therefore no systemic effect.
DUSTING POWDERS
Are finely divided powders introduced into the body cavities such as the ears, nose, throat, tooth sockets and vagina
INSUFFLATIONS
(powder blower) is usually used, pressure
aerosols are being employed especially for potent drugs.
Insufflator
administered by inhalation with the aid of dry-powder inhalers, which deliver micronized particles of medication in metered quantities
AEROSOL POWDERS
After the powders have been properly mixed by the geometric dilution, it may be divided into individual units based upon the dose.
DIVIDED (CHARTULAE)
dry mixture of the ampicillin and diluents and
stabilizing agents – anti-infectives
Ampicillin Soluble Powder -
used as a topical anti-infective
Polymyxin B Sulfate and Bacitracin Zinc Topical Powder, USP
mixture of Clioquinol, lactic acid, zinc stearate, and lactose - vaginal insufflation as an antitrichomonal
Compound Clioquinol Powder, USP
employed as a topical dusting powder in the
treatment of mycotic infections
Nystatin Topical Powder, USP
vaginal Insufflations as antimicrobial
Compound Iodochlorhydroxyquin Powder NF
local anti-infectives for diaper rash in infants
Methylbenzenethonium Chloride Powders NF
Are prepared agglomerates of smaller particles
GRANULES
granules usually in a size of
4 to 12 sieve size range
granules method of preparation
o Dry Granulation (Fusion)
o Wet Granulation
induce vomiting
emetic drugs
prevent vomiting
antiemetic drugs
increase the flow of urine;
Diuretic drugs
increase respiratory tract fluid
expectorant drugs
evacuate the bowel
cathartics or laxatives
study of the biochemical and physiologic effects of drugs and their mechanisms of action
pharmacodynamics
deals with the absorption, distribution, metabolism or biotransformation, and excretion (ADME) of drugs
pharmacokinetics
applies pharmacologic principles to the study of the effects and actions of drugs in humans
clinical pharmacology
transit through the liver and exposure to the hepatic enzyme system
first pass effect
deals with the adverse or undesired effects of drugs.
Toxicology
must be considered before the development of a pharmaceutical formulation
Physical characteristic Chemical characteristic Solubility Partition coefficient dissolution rate physical form Stability
Enhanced aqueous solubility may be achieved by preparing more soluble derivatives of the parent compound
salts or esters
chemical complexation
reducing the drug’s particle size
preference for lipids
lipophilic
preference for an aqueous phase
hydrophilic
speed at which a drug substance dissolves in a medium
dissolution rate
considered a process of solution and diffusion, with the penetrant dissolving in the plastic on one side and diffusing through to the other side
Permeability
True or False
Glass containers are less permeable than
plastic containers
True
a term used to describe the movement of components of a container into the contents
Leaching
devised to make possible the administration of drugs in measured and accurate amount
dosage form
Physical properties
physical description, particle size, crystalline structure, melting point, and solubility
relate to its ability to get to a site of action and elicit a
biologic response.
Biologic properties
FD&C dyes
which may be used in foods, drugs, and cosmetics
D&C dyes
some used in drug, some for cosmetics and some for medical devises
external D&C dyes
use of which is restricted to external parts of the body, not including the lips or any other body surface covered by mucous membrane
powders were found to be a convenient mode of administering drugs derived from hard vegetables such as
roots (e.g., rhubarb), barks (e.g., cinchona), and
woods (e.g., charcoal)
reduction of the particle size of a solid substance to a finer state
Comminution
is used to facilitate crude drug extraction, increase the dissolution rates of a drug, aid in the formulation of
pharmaceutically acceptable dosage forms, and enhance the absorption of drugs
Comminution
particles are passed by mechanical shaking through a series of sieves
SIEVING
Sieving range
from 40 to 9500 micrometers, depending upon sieve sizes
Particles are sized through the use of calibrated grid
background or other measuring devise
Microscopy
In which particles is determined by measuring the
terminal settling velocity of particles through a liquid medium in gravitational or centrifugal environment
SEDIMENTATION RATE
particle size is determine by the reduction in light reaching the sensor as the particle, dispersed in a liquid or gas, passes through the sensing zone
LIGHT ENERGY DIFFRACTION/LIGHT SCATTERING
a pulsed laser is fired through an aerolized particle spray and photographed in three dimensions with a halographic camera, allowing the particles to be individually imaged and sized
LASER HOLOGRAPHY
Is based on the principle that a particle, driven by an
airstream, will impact on a surface in its path, provided that its inertia is sufficient to overcome the drag force that tends to keep it in the airstream
CASCADE IMPACTION
SIEVING
40-9500 micrometers
MICROSCOPY
0.2-100 micrometers
SEDIMENTATION RATE
0.8-300 micrometers
LIGHT ENERGY DIFFRACTION/LIGHT SCATTERING
0.2 - 500
micrometers
LASER HOLOGRAPHY
1.4 - 100 micrometers
Range of aerosol powder
1-6 micrometers
method used in divided chartulae
block and divide
Granules are usually in __ sieve size
4-12 sieve size
Method of preparation
Dry granulation
Wet granulation
solid dosage forms usually prepared with the aid of suitable pharmaceutical excipients
Tablets
Manufactured with tablet machine capable of exerting great pressure or compacting the powdered or granulated tableting material
Compressed Tablets (C.T.)
prepared by subjecting the fill material to more than a single compression
Multiple compressed tablets
inner tablet is the
core
outer tablet is the
shell
Compressed tablets may be coated with a
colored or an uncolored sugar layer
Sugarcoated Tablet
should be water soluble and quickly dissolve after swallowing
Purpose of sugarcoated tablet
protect the enclosed drug from the environment
provide a barrier to objectionable taste and smell of the drug
Disadvantages of sugarcoated tablet
time and expertise needed in the coating
process and increased shipping costs
Coating is made of thin layer of a polymer capable of forming a skin-like usually colored film over the tablet.
Film-Coated Tablets (F.C.T.)
Capsule-shaped compressed tablet with 1/3 the size of capsule with the same amount of fill, more ease in swallowing & more tamper evident
Gelatin Coated Tablet
delayed release features, designed to pass the stomach to the intestines where the tablet will disintegrate allowing drug dissolution & absorption
Enteric-Coated Tablets (E.C.T.)
Flat, oval tablets intended to be dissolved slowly in the buccal pouch
Buccal tablets
Designed to erode promptly underneath the tongue for rapid drug effect
Sublingual Tablets
Disc-shaped solid forms containing a medicinal substance in a hard candy or sugar base. Meant to dissolve slowly for localized effect or systemic effect
Lozenges or troches
Have rapid disintegration when chewed or allowed to dissolve in the mouth, have a creamy base usually specially flavored and colored mannitol
Chewable Tablets
Meant for large-sized tablets given to children and adults with difficulty in swallowing solid dosage forms
Chewable Tablets
prepared by compressing granular effervescent salts that release gas when in contact with water
Effervescent Tablets
Small & cylindrical, very soft, soluble & designed to dissolve rapidly
Molded Tablet Triturate (M.T.T.)
Prepared by compression (limited pressure) usually containing potent substance
Compressed Tablet Triturate (CTT)
used for diluent in Compressed Tablet Triturate
Sucrose and lactose
Used by physicians for extemporaneous preparations of parenteral
Hypodermal Tablet (H.T.)
Used by pharmacists when compounding prescriptions and not dispensed to patients.
Dispensing Tablets (D.T.) or compounding tablets
Designed to disintegrate and release their medication and therefore are devoid of special rate controlling features like coating and other way
Immediate Release Tablets (I.R.)
Characterized to dissolve within 10 seconds to 1 minute.
Instant Disintegrating/ Dissolving Tablets
Designed to release their medication in a predetermined manner over an extended period of time
Extended-Release Tablet (E.R.) /Controlled Release (C.R.)
Uncoated and bullet- or ovoid- shaped tablets for localized effect. Prepared by compression and shaped to fit smugly into plastic inserter devices
Vaginal Tablet/Inserts
10 tablets are individually weighed and average weight calculated
USP Weight Variation Test
Compendial requirement for content uniformity
85% to 115% of the label claim
less than 6% standard deviation
Tablet thickness: is determined by
▪ the diameter of the die
▪ the amount of fill
▪ the compactibility of the fill material
▪ the force of pressure applied during compression
Affects its disintegration & drug absorption. The greater the pressure, the harder the tablet. It should be hard enough to resist breaking during the normal handling and yet soft enough to disintegrate properly after swallowing
Tablet hardness
minimum requirement for a satisfactory tablet
force of 4 kilograms as determined by hardness tester
tendency to crumble by allowing it to roll and fall within the rotating machine
Tablet friability
True or false
A maximum weight loss of not more than 1% of the weight of the tablets being tested is acceptable.
True
Tablet Disintegration Test
▪ Uses a basket-rack assembly containing 6 open ended transparent tubes held vertically upon a 10-mesh stainless steel wire screen.
▪ The basket is raised and lowered in the immersion fluid (water at 37oC) at a frequency of 29-32 times per minute. Result: the residue of the tablet on the screen is a soft mass having no palpable inner core.
Disintegration time ranged from 2 mins. to 4 hours depending upon the monograph.
Tablet Disintegration Test
For enteric coated tablets
test is done in a simulated gastric fluid for 1 hr. No sign of disintegration must be seen
Pooled dissolution testing
• Samples coming from different batches placed in individual dissolution vessel in the apparatus or multiple dosage units in a single vessel. This recognizes the concept of batch characteristics
3 METHODS FOR COMPRESSED TABLET
WET GRANULATION
DRY GRANULATION
DIRECT COMPRESSION
Fillers
lactose and microcrystalline cellulose
to facilitate adhesion of powder particles. Starch, povidone, methylcellulose.
Binder
– to improve the flow of granules from the hopper to the die; prevent adhesion to the punches and die during compression; reduce friction between tablet and die’s wall during tablet ejection and provide tablet sheen
Lubricant
Fluid-bed granulator which performs the blending, granulating, drying into 1 continuous process
Fluid-bed Process
Powder mix is mixed, wetted, agglomerated and dried using microwave
Microwave Vacuum Process
the powder mixture is compacted to large pieces and broken down or sized into granules
DRY GRANULATION
compress tablet formulation within a steel die cavity by the pressure exerted by the movement of the two steel punches (upper and lower).
Tableting machine
Imperfections of tablets
- Laminations – horizontal striations
- Tablet capping – the top of tablet separates from the whole
- Tablet splitting
Reasons OF Imperfections of tablets
- particles have no time to bond due to fast high-speed production
- air is entrapped during direct compression
- punches not clean
- aging
appropriate for chemicals with flowing and cohesive properties
DIRECT COMPRESSION
to remove traces of loose powder adhering to the tablets following compression
Tablet Deduster
Tablets are coated
- to protect from air and/or humidity
- mask the taste
- provide characteristics of drug release
- to provide aesthetics or distinction to the product
tedious, time-consuming and needs expertise of
qualified technician and the product doubles the size and weight
Sugarcoating
– provides a thin, skin-tight coating of a plastic material over the compressed tablet
Film coating
to produce thin smooth film. Cellulose acetate
phthalate
Film former
to provide water solubility/ permeability
for body fluids to penetrate through and make the drug
available. Polyethylene glycol
Alloying substance
to produce elasticity/flexibility to the coating & provide durability. Castor oil
Plasticizer
Advantages of direct compression
Size and wt. almost the same as the tablet, more resistant to destruction by abrasion, markings can be embossed on the coating
maybe accomplished through coating with enough thickness or coating which allow dissolution at a pH 4.9 or higher.
Example is shellac
Enteric coating
pray coating of powder, pellets, granules or tablets held in suspension by a column of air
Fluid –Bed or Air Suspension Coating
the coating material (granulation or powder
form) is compressed into the tablet core
Compression Coating
solid dosage forms in which one or more medicinal &/or inert substances are
enclosed within a small shell or container generally prepared from a suitable
form of gelatin
Capsules
HARD GELATIN CAPSULES- Also referred to as
“DFC” (Dry Filled Capsule)
Manufactured into 2 sections
the capsule body and a shorter cap
HARD GELATIN CAPSULES are made up of
gelatin, sugar & water
Colored with various FD&C and D&C dyes and made opaque by adding agents such as
TITANIUM DIOXIDE
