DFDS EXAM 2

Route of Admininistration

path by which a drug, fluid, poison, or other substances are brought into contact with the body

First Pass Effect

Most blood supplying the GI tract travels to the liver first before it goes to the rest of the body —> detoxifies + metabolizes drug :. reduces amount of drug in body (lower bioavailability)

90% of drug gets metabolized + destroyed in the liver before it gets to heart (hepatic portal system)

occurs when medication is administered orally

greater the effect, the lesser the agent will reach systematic circulation

Enteral (RoA)

systemic

administering a drug through the gastrointestinal (GI) tract or via the mouth or rectum

oral (mouth)

sublingual (under tongue)

buccal (cheek)

rectal (rectum)

gastric/ duodenal feeding tube

Parenteral (RoA)

systemic

injections

intravenous

intramuscular

subcutaneous

intradermal

Mucosal (RoA)

local

inhalation

intra-nasal

rectal

vaginal/urethral

Local RoA

does not circulate through the entire body

ocular

otic/aural (ears)

topical (skin)

Systemic RoA

circulates in blood

enteral, parenteral, transdermal (skin to blood), mucosal

Oral Route

most common route of drug administration

natural, uncomplicated, convenient and safe

drug taken through oral cavity

absorption takes place at any point along GI tract (oral cavity, stomach, small/ large intestine)

intestines are major site of drug absorption

tablets, capsules, emulsions, solutions, suspensions, syrups

Oral Route Advantages

convenient

relatively safe

economical

natural

no need for sterilization (bc of stomach acid)

Oral Route Disadvantages

large amount gets metabolized through first-pass effect

fraction that does not get absorbed gets excreted

absorption can be variable

food-drug interactions

irritation (nausea and vomiting)

unpleasant taste

some drugs are inactivated by gut (insulin)

effects are too slow for emergencies

cannot be given to unconscious, vomiting, or uncooperative patients

Sublingual RoA

drugs are taken as smaller tablets which are held in the mouth under the tongue

drug dissolves promptly and provides rapid drug effects

fastest roa

systemic delivery of potent drugs (eg nitroglycerine)

Buccal RoA

tablets designed for attaching to the buccal pouch (gum) for release of drugs and absorption through oral mucosa

erode slower than SL tablets

systemic delivery of potent drugs (eg nitroglycerine)

Sublingual/ Buccal Advantages

rapid absorption

drug stability

avoids first-pass effect

quick termination

can be self-administered

economical

Sublingual/ Buccal Disadvantages

inconvenient

small doses only (for SL)

unpleasant taste of some drugs

some drugs may be swallowed before adequate absorption

only some drugs are absorbed via SL/BL

Rectal Route

uses rectum as RoA for medication + other fluids

can be used for local or systemic effects

dosage forms: suppositories, enema solutions, emulsions, suspensions

systemic delivery of potent drugs

local delivery of drugs (e.g. analgesics)

Rectal Route Advantages

reduced first-pass metabolism

useful in children, elderly, unconscious/ vomiting patients

higher drug concentrations can be achieved

Rectal Route Disadvantages

irritation/inflammation of rectal mucosa

absorption is slow/ erratic (dependent on where its absorbed)

patient inconvenience/ poor acceptance

potential incomplete absorbance

Mucosal Route

drug delivered via absorptive mucosa in various easily accessible body cavities

BL/SL: systemic delivery of potent drugs

Pulmonary (Nasal): local delivery of drugs (e.g. antihistamine sprays)

Ocular: local delivery of drugs (e.g. pupil dilation, cataracts)

Vaginal: local delivery of drugs (e.g. induction of labor)

Rectal: systemic delivery of potent drugs, local delivery of drugs (analgesics)

Mucosal Route Advantages

achieves rapid onset of action

avoids first-pass effect

withstand acid-labile drugs

Mucosal Route Disadvantages

not as convenient as oral administration

Parental Route

injections

intravascular (IV): placing drug directly into bloodstream

intramuscular (IM): drug injected deep into skeletal muscle (~5 mL); usually admininstered in gluteal/ lumbar muscles

subcutaneous: absorption of drugs from the subcutaneous tissues (~2 mL); forearm, upper arm, thighs, buttocks

intradermal: drug injected into dermis of skin (~0.1 mL)

inthracal injection: injection into the spinal canal to reach CSF (brain); useful for spinal anesthesia, chemo, or pain management

Intravascular (IV) Route Advantages

rapid onset

continuous titration

accurate dose

larger volume over longer period of time

Intravascular (IV) Route Disadvantages

dangerous (rapid onset of pharmalogical action; no space for error)

overdose (no recall/ stopping absorption)

sterile/ aseptic techniques required

Topical Route

local action of drug applied on skin

dermal: rubbing on skin

eye drops

ear drops

vaginal (topical estrogens, antibacterial)

Transdermal Route

absorption of drug through skin (systemic action)

e.g. fentanyl patches

easy to use

achieves stable blood levels

avoids first-pass metabolism

drug must be potent (otherwise patch gets too big)

potential skin irritation

Inhalation Route

rapid delivery across large surface area of mucous membranes of respiratory tract + pulmonary epithelium

local effect (bronchodilation for asthma)

systemic effect (lungs)

dosage forms: aerosols, gaseous/ volatile agents

Intranasal Route

drug administration directly into nose (e.g. decongestant nasal sprays)

rapid absorption/ onset activity

can be used for systemic effect (bloodstream)

ease of administration

bypasses blood brain barrier

only low volume (20-200µM)

not feasible for drugs with higher molecular weight

Longest Duration of Action

transdermal patch

Short Duration of Action

quick acting drug

Long Duration of Action

long acting drug

Where Duration of Action and Onset of Effect Meet

first time drug is theraputically active

Most Rapid Onset of Action

sublingual, intravenous, and buccal RoA

Shortest Duration of Action

Sublingual

Onset of Action

time at which

drug concentration ≥ MEC (minimum effective concentration)

Duration of Action

time during which

drug concentration ≥ MEC (minimum effective concentration)

Monophasic Solutions (Liquid Dosage Forms)

only one phase; uniform phase in which the drug is completely dissolved in the solvent; homogeneous

aqueous solutions, non-aqueous solutions

commonly used for oral admin, topical, ophthalmic, nasal and specialized uses

syrups, elixirs, tinctures, spirits, aromatic waters, liniments, collodions

solution contain drug in suitable solvent, color, flavors, sweeteners, stability enhancers etc

Multiphasic Solutions (Liquid Dosage Forms)

2+ distinct/immicible phases; drug is dispersed rather than dissolved completely; contains insoluble active ingredients

suspensions (particles in water), emulsions (oil in water), colloids (extremely fine particles in water)

require special stabilizing agents to ensure API is evenly distributed

Solutions Advantages

compliance

ease of administration

dose variation is simple

Solutions Disadvantages

impacted by first-pass effect

poor chemical stability

microbial growth can occur without added preservatives

light sensitivity but can be overcome with tinted bottles

transport and storage (bulky)

expensive to manufacture

not all drugs are well-soluble

Hypertonic Solution

cells shrivel

Hypotonic Solutions

cells swell

Isotonic Solutions

no change in cell volume

ideal condition

Solvent Selection

Dissolution Power

Clarity (cannot be any haze)

Compatibility with human fluids

Palatability, Color, Odor

Price cannot be too expensive

Commonly Used Solvents

water; auxillary solvents (alcohol, glycerin, propylene glycol) may be added

organic solvents (acetone, isopropyl alcohol) too toxic, but used for research

fixed oils (corn oil, cotton seed oil, penut oil, sesame oil) used for more insolubke drugs, or oleaginous injections

Syrups

concentrated aqeuous preparations of sugar or sugar substitue with/without medicinal + flavoring agent

very sweet + viscous

sucros (60-85%)

flavored/unflavored

sugar content is used to mask taste + odor of liquid medications

contains preservatives (parabens or benzoic acid 0.1-0.2%)

Simple Syrup NF Syrup

stable, crystallization resistant

sucrose 85% w/v

no preservative needed bc sugar saturated water molecules disallowing microbial growth

Antihistamine Syrup

uses alcohol as co-solvent

purified water = primary solvent

sodium benzoate = preservative

Solution With Aid Of Heat (Syrup Preparation)

quickest method of preparation

used for thermostable medications + non-volatile materials

sugar is first added to purified water, and then heat is applied until sugar is dissolved, then other heat-stable components are added to hot syrup

volume is adjusted by adding purified water

Solution With Aid Of Heat Disadvantages

can cause inversion (hydrolysis of sugar)

darkening of color due to carmelization

sugar decomposed due to excessive heat, susceptible to microbial growth

syrup cannot be sterilized by autoclaving

Agitation Without Heat (Syrup Preparation)

all ingredients placed in large vessel

agitated until immiscible

medication dissolved in minimum solvent then incorporated into syrup

stable but time consuming

Addition of Sucrose to Prepared Medicated Liquid

used if medication is to be prepared from tincture or fluid extract

sucrose is added to medicated solution

if it is soluble, it is directly added to simple syrup

caution: alcohol-soluble components may precipitate when added to syrup

no heat → stable

Percolation (Syrup Preparation)

purified water/ source of medicinial component is passed slowly though bed of cystalline sucrose

sucrose dissolves and forms syrup

useful when source of drug is naturally occurring/ plant based

e.g. ipecac syrup

Elixir

contains alcohol (50-40%), self-preserving if alc. content is more than 12%

less sweet and less viscous than syrups

main ingredients: alcohol, water, co-solvents (glycerin), flavoring agents

less efficient in masking taste than syrups

more stability + easier to prepare than syrups

alcohol content = disadvantage for children

aqueous solution INTO water to avoid precipitation

Medicated Elixir

for therapeutc benefit

antihistamine elixirs; basic amine prepared as a salt, pH is critical when diluted

Nonmedicated Elixir

flavoring vehicle for compounding/ dilution of medicated elixirs

e.g. simple syrup NF (ready-made)

Tincture

Alcoholic/ hydroalcoholic solutions prepared from vegetable materials/ chemicals

highest alcohol concentration → 15-80% for dissolution/ preservation (does not need preservative bc alcohol concentration > 12%); needs to be stoppered and protected from high temps + is light sensitive

prepared by percolation or maceration (crushed in closer container

mixing with other solutions may cause precipitation

Solution Physiochemical Term

molecular dispersion of 2+ subtances

Solution Pharmaceutical Term

liquid preparations that contain one or more substances dissolved in a suitable solvent/ mixture of miscible solvents

Purified Water as Solvent

tap water only used for cleaning, not medicinal purposes

purified water, USP: solid content is less than 0.001% (w/v) → used for aqueous dosage forms

preparation: distillation, ion exchange, reverse osmosis

Alcohol as Solvent

used as solvent or co-solvent, good water miscibility, good dissolution power, antimicrobial properties

alcohol + water = hydroalcoholic solutions

more than 12 years of age restricted alc. content: <10%

6-12 years of age restricted alc. content: <5%

under 6 years of age: <0.5%

Diluted Alcohol, NF

50% alcohol, 50% purified water

actual strength is higher bc of 3% decrease in volume upon mixing

Rubbing Alcohol

70% ethyl alcohol by volume and rest is water + denaturants (for potential abuse)

contains bitter substances and organic additives that cannot be separated

rubefacient (makes skin red), soothing rub, germicide, skin clearing

vehicle for topical preparations

Isopropyl Rubbing Alcohol (IPA)

70% IPA in water with/without colors, stabilizers, perfume oils

rubefacient externally, soothing rub

vehicle for topical preparations

disenfectant for injections

does not need denaturation bc it’s less likey to be abused

Glycerin

clear, liquidy syrup with sweet taste

miscible with both alcohol and water

can be used to reduce alcohol content of preparations

stabilizer

viscous→ drug disolves slowly

compared to alcohol in dissolution power

Aromatic Waters

no longer used in widespread use for drug delivery/ administration

used as purfuming or flavoring agent

clear aqueous solution saturated with volatile oils

Spirits

Alcoholic

usually >60% alcohol

forms milky solution with water

used as flavoring agent, or for therapeutic value of oil

used orally, externally, or by inhalation

prepared by simple solution, maceration or distillation

e.g. camphor spirit, orange spirit, peppermint spirit

Liniment

alcoholic, oleaginous solution intended to be rubbed on skin

should be stored in tight containers

must be indicated clearly not to be taken orally

e.g. camphor

Collodions

clear liquid preparation composed of Pyroxylin (cotton derivative) dissolved in solvent mixture, with/without added medication

when applied to skin with fine camel’s hair brush, solvent rapidly evaporates, leaving filmy residue of pryroxylin

provides occulsive protective coating on skin

uncomfortable due to lack of flexibility

intended of external use only

Disperse Systems/ Dispersions

hetergeneous systems

contain particulate matters/ globules distributes throughout medium

contains two phases: dispersed/internal and continuous phase

Dispersed/ Internal/ Discontinous Phase of Dispersions

suspended particles/ globules

Continuous/ Dispersion Medium/ Dispersing Phase of Dispersions

suspension liquid

Molecular Dispersion

< 1nm (can’t see with naked eye)

particles invisible in electron microscope, undergo rapid diffision

e.g. glucose solution, saline

Colloidal Dispersion

1-500 nm

particles invisible in ordinary microscope but seen in electron microscope

diffuse/ disperse slowly

e.g. milk, fog, paint, colloidal polymer dispersions

Fine Dispersions

0.5-10 nm

particles visible under ordinary microscope

particles do not diffuse

e.g. magmas and gels

Coarse Dispersion

10-50 μm

particles visible under ordinary microscope

particles do not diffuse

pharmaceutical suspensions

e.g. blood, suspensions, emulsions

Suspensions

dispersion of finely divided solid materials suspended in liquid medium in which drug has minimim solubility

e.g. liquid amoxicillin, liquid childrens ibuprofen

Suspensions Advantages

good for insoluble drugs

greater oxidation against hydrolyis and oxidation

masks disagreeable taste (drug is already dissolved)

easier to swallow

depot therapy (slower release)

topical dosage form for water insoluble drugs

Suspensions Disadvantages

particles can sediment (irreversible)

difficult maintaining uniformity + accuracy of doses

storage/transport

more difficult manufacturing process

inadequate dispersion

Desired Features of Suspensions

should settle slowly but redisperse quickly upon mild shaking

should avoid forming hard cake (sedimenting)

easy to pour from bottle, easy to spread on skin, easy to flow through syringe

sufficient physical, chemical, and microbiologic stability

pleasant taste

Flocculated Suspension

more desirable

settles slower, not that compact when settled (weakly bonded)

easily resuspendable

less prone to cake

when formulated with structured vehicle, suspended agent is added (+ flocculated agent)

addition of flocculated agent

Deflocculated Suspension

slowly settles to very compact sediment (cake)

height of sediment is small (closesly packed arrangement)

potential excipients can minimize cake formation

difficult to redisperse

prepared with suspending agent

Viscosity (Property of Suspension)

ratio of force applied to rate of flow of a liquid

V = F (force)/ G (flow of liquid)

G = (1/V)F

rate of flow is inversely proportional

influences physical stability of suspensions

Newtonion Flow (Classification of Flow)

water

the larger the slope the lower the viscosity

proportionate increase

Plastic Flow (Classification of Flow)

ointments

mechanical force starts flow

when slope is greater, viscosity is lower

G is linear after certain force applied

B>A

Pseudoplastic Flow

flocculated suspensions

creams

moment force is applied rate of flow (G) increases

B>A

Dilatant Flow

Deflocculated suspensions

toothpaste

resists flow; if too much flow it becomes hard solid mass

A>B

Thixotropic Flow

vibrations cause gel → solution change

when force stops, change is reversed

Wetting Agents (Suspensions)

most important for initial dispersion during preparation of suspension

the smaller the contact angle, the higher the wetting (ranges from 0-180)

Suspending Agents (Suspensions)

reduces rate of sedimentation (to increase viscosity so particles don’t sink)

enhances appearance of suspension

preferable exhibit psedoplastic + thixotropic flow

types: natural (xantham gum), synthetic (methyl cellulose), clays (bentonite)

Flocculated Agents (Suspensions)

added to flocculated suspensions

added to reduce + control particle surface charge to optimum level

assures particle dispersion for sufficient period of time and prevent formation of a compact sediment that is difficult to redisperse

Electrolytes as Floccuating Agents (Suspensions)

reduce electrical barrier between particles (sodium phosphate, potassium chloride)

Important Points When Choosing Floccuating Agents

1. surface charge of drug particles (floccuating agent has to be opposite)

2. valency of electrolyte (Na+1 can only attract one molecule, Cl+2 is a stronger electrolyte bc it can attract 2 drug molecules)

3. electrolyte concentration

Polymers as Flocculating Agents (Suspensions)

higher molecular weight compounds

useful for drugs that don’t carry a charge

act as FA by conjoining different drug particles by forming bridges to create flocs

can mask charge on particles

ex) xanthum gum, polyacrylamide

Surfactants as Flocculating Agents (Suspensions)

ionic -→ reduce charges

nonionic → form protective layer around drug particle

Ionic Surfactants (Suspensions)

act as FA by reducing charge on the particle surface

work like electrolytes; screen particles + attract molecules together

e.g.) docusate sodium

Nonionic Surfactants (Suspensions)

act as FA by forming a protective layer around particle to prevent aggregation

e.g.) tweens or spans

Stokes Law

rate of sedimentation

diameter of particles (d): proportional

density of internal phase (ps): proportional

density of external phase (po): inverse

viscosity of medium (n): inverse

Rate of Sedimentation vs Diameter of Particles (d)

proportional relationship

Rate of Sedimentation vs Density of Internal Phase (ps)

proportional relationship

Rate of Sedimentation vs Density of External Phase (po)

inverse relationship