802 Exam 1

this one doesnt suck

dosage form

optimized drug product designed to release the drug to achieve maximum safety and efficacy

design considerations for dosage forms

route of admin disease state drug physiochemical characteristics drug biopharmaceutical characteristics patient production requirements

polymorphism

dosage forms with the same chemical composition but different internal structures like packing and conformation...

what are the effects of polymorphism?

changes in the physiochemical properties of a drug like solubility and melting point

what can changing particle size effect?

dissolution rate bioavailability taste color stability flow characteristics sedimentation rates (suspensions)

what can effect drug solubility?

chemical structure particle size pH

why is the pH-solubility profile important for the dosage form design and drug delivery?

extremes in pH may not be compatible with physiologic requirements changes where the drug can be absorbed

what are the common methods to increase solubility of drugs?

salt form solution complexation with hydrophilic macromolecules

which of the following is true regarding polymorphs 1: drug polymorphs have different crystal structures 2: drug polymorphs can have different solubility 3: drug polymorphs have different molecular weight 4: 1 and 2 5: all of the above

4: 1 and 2

what is the dissolution rate?

the time taken by the drug to dissolve prior to absorption

what dosage form is optimal when rapid dissolution is needed

intramuscular suspensions

what are the factors affecting dissolution

particle size (surface area) chemical nature of the drug (base, acid, salt, neutral) physical state of the drug pH solubility profile

what pharmacokinetic features can dissolution effect

overall bioavailability onset of activity duration of actin efficacy

how is absorption effected by pH

many drugs are ionizable and the degree of ionization is significantly affected by pH which changes the extent of dissolution (non-ionized usually preferred)

what is the measure os the lipophilicity of a compound?

partition coefficient

what is the partition coefficient useful for?

estimating how a drug will behave in a physiological environment

what is the goal of adjusting lipophilicity of a durg?

to make it soluble enough in physiological conditions but lipid enough to be absorbed

what does logP tell us about a drug

if it favors lipid or water based environments

what is log p

the log of the ratio of drug in octanol (oil phase) vs drug in water

what are the most common mechanisms of drug degradation

hydrolysis - rxn with h2o resulting in inactive compounds oxidation - loss of electrons leading to an inactive compound

what are excipients

inactive pharmaceutical ingredients

what are the reasons to add excipients

improve -drug stability -taste -dissolution/absorption

what is the purpose of adsorbents

hold other molecules to its surface by physical or chemical means

what are the characteristics of disease that effect route of drug adminstration

type severity target organ treatment vs prevention

what are the characteristics of the patient that effect route of drug adminstration

age physical condition disease patient compliance

what are biopharmaceutical properties of the drug

permeability pharmacokinetics (ADME) bioavailability dose (potency)

what are the characteristics of a drug that is easy to formulate in carious dosage forms?

high solubility high permeability

what is drug absorption dependent on

physiochemical properties permeability site of admin route of admin

what are admin considerations for very potent drugs

accuracy and uniformity

what can drug ionization effect?

solubility lipophilicity permeability

what is a nonelectrolyte

compound that does not ionize in water

what are examples of nonelectrolytes

sugars alcohols ethers esters ketones aldehydes most amides

what is an electrolyte

compound that ionizes in water or an aqueous environment

what is the difference between a strong electrolyte and a weak electrolyte

strong electrolytes completely ionize (NaCL) while weak electrolytes only partially (acetic acid, ammonia)

what are examples of weak acids

carboxylic acids sulphonic acids phenols thiols imides

what are examples of weak bases

aliphatic amines aromatic amines n-heterocycles

define pKa

the measure of strengths of weak acids and bases

remember pKa only tells the measure of strength not if the compound is an acid or base

lower is stronger

what are the factors effecting pKa

ionizing group molecular size medium effects substituent effects

what are medium effects

solution pH solvent

what are substituent effects

type (leaving) position

which of the following is true a: phenols are weakly acidic substances b: sodium hydroxide is a strong base c: aromatic amines are weakly acidic substances d: a and b e: all of the above

d: a and b know aromatic amines are weakly basic not acidic

what is a polyprotic system

acid or bases that can donate or accept more than one proton examples include amino acids and proteins

which of the following is the strongest acid a: acetaminophen (pKa 9.5) b: ibuprofen (pKa 4.8) c: salicylic acid (pKa 2.98)

c: salicylic acid

describe what the henderson hasselbalch equation tells us

the relationship between pH and pKa it determines how much a compound is ionized to an acid or base

what occurs when pH = pKa

50% of the drug exists in ionized form and the remaining is in non-ionized form

describe buffer capacity

a measure of the efficiency of a buffer in resisting changes in the pH value a higher buffer capacity is a more resistant buffer

what is buffer capacity dependant on

ratio of salt to the acid or base (optimal ratio is 1:1) total buffer concentration

what is the need for buffering pharmaceutical formulations

maintain solubility or weak acidic or basic drugs improve stability maximize preservative efficacy (think ocular formulations) reduce discomfort and irritation

what is the relationship between pH and pKa and ionization state

the farther away from zero the higher the ionization state (scale is -4 to 4)

which of the following statements is true a: pKa value does not tell you whether the compound is acidic or basic b: drugs with multiple pKa values exist c: pKa value can help understand the ionization of drug inside the body d: a and b e: all of the above

e: all of the above

why is drug solubility important

to develop stable and efficacious solutions to determine the necessary conditions for manufacturing impacts on dissolution, absorption and bioavailability to develop suitable strategies for the delivery of poorly soluble drugs crystallization process

define solution

mixture of two or more components that form a homogenous mixture

what are the factors affecting drug solubility

temperature particle size (insoluble drugs) crystal properties (think polymorphism) chemical structure pH

what are the two types of solutions

saturated solutions and unsaturated solutions

describe a saturated solution

equilibrium is established between dissolved solute at a definite temp OR a solution that contains the maximum amount of solute at a definite temp

define unsaturated solution

containing the dissolved solute in a concentration below that necessary for complete saturation at a definite temperature

true or false: the polarity of a solvent play a role in determining solubility

true think of the like dissolves like rule

what are the three types of solvents

polar (water, alcohols) non-polar (hydrocarbons, oils, lipids) semi-polar (ketones, polyethylene glycol)

what are the characteristics of a polar solvent

high dipole moment and high dielectric constant

what are the characteristics of a non-polar solvent

low to no dipole moment and low dielectric constant

what are the characteristics of a semi-polar solvent

increase miscibility of polar and non-polar solvents with each other

true or false: a molecule forming intramolecular hydrogen bonds increases its solubility in water

false

which of the following statements is true a: polar drugs are likely to dissolve more in polar solvents b: drug solubility can increase with the decrease in particle size c: water is a polar solvent d: a and b e: all of the aboce

e: all of the above

reminder be able to determine is a drug is a weak acid or base based on a solubility graph

weak acid starts low ends high weak base starts high ends low

true or false: different salts of the same drug will have different aqueous solubility

true!

what is the ideal log P range for a drug

0 - 3.5 (about this is not a rule)

BCS Class 1

high solubility high permeability think metoprolol

BCS 2

low solubility high permeability think celecoxib

BCS Class 3

high solubility low permeability think acyclovir

BCS Class 4

low solubility low permeability think paclitazel

name the techniques for improving solubility

salt formation particle size reduction altered or reduced crystal structure co-crystallization co-solvents solid dispersions complexation emulsion

what are some of the solvents involved in solubilization

ethanol propylene glycol glycerol polyethylene glycol (PEG)

what are the methods for solid dispersions

hot melt extrusion spray drying

what is complexation

adding a cyclodextrin to a hydrophobic drug to improve solubility

what is inclusion conplexation

basically the cyclodextrin forms a cap around the drug and improves solubility

define solution in physicochemical terms

can be prepared from combination of solid liquid and gas

define solution in pharmaceutical terms

solutions are liquid preparations containing drug or chemical substances dissolved in solvent of mixture of mutually miscible solvents monophasic system

what are the advantages of solutions

homogenous and monophasic easy to measure accurately easy to swallow amenable to administration no lag time till dissolution

disadvantages of solutions

not a unit dosage form solution chemistry poses stability issues (physicochemical degradation, reactivity, shorter expiry than other dosage forms) sterility concerns mask taste

what are the types of pharmaceutical solutions

solutions syrups elixirs spirits aromatic waters tinctures sprays collodions liniment

define syrup

aqueous solutions containing a high concentration of sugar

define elixir

exliirs are flavored sweetened hydro-alcoholic solutions for oral use

define spirit

aromatic materials in alcohol

define aromatic waters

aromatic material in water

define tincture

alcoholic solutions prepared by extracting active constituents from crude drugs

true or false: tinctures spirits and elixirs may be useful for delivering lipophillic constituents at a required concentration

true

define spray

aqueous or oleaginous solutions in the form of coarse droplets or as finely divided solids to be applied topically (nasal/skin)

define collodions

liquid preparations composed of nitrocellulose in a solvent mixture (alcohol + ether)

which of the following pharmaceutical solutions do not contain alcohol a: elixir b: syrup C: spirit d: tincture

b: syrup

what should be considered when choosing a solvent

solubility low toxicity compatibility chemical inertness clarity viscosity palatability odor color cost

solvents used for liquid preparations

1 alcohol 2 diluted alcohol 3 alcohol rubbing 4 glycerin 5 isopropyl rubbing alcohol 6 propylene glycol 7 purified water 8 fixed oils

when is dehydrated alcohol used

when water free alcohol is desired

true or flase: when mixed with water ethylalcohol forms a hydroalcoholic mixture that dissolves both alcohol soluable and water soluble substances

true!

what is the alcohol limit for children under6 years of age

0.5%

what is the alcohol limit for children 6-12 years of age

5%

what is the alcohol limit for ages 12 and up

10%

which of the following solvents will NOT be preferred for oral pharmaceutical solutions a glycerol b propylene glycol c isopropanol d ethanol

c isopropanol this is TOXIC and for external use only

true or false purified water is intended for use in the preparations of aqueous dosage forms including parenteral administration (injections)

FALSE purified water cannot be used in parenteral administration but can be used in all other aqueous dosage forms

during distillations which portions of the aqueous distillate must be discarded

the first 10-20% which contains many forgein volatile substances and the last 10% because distillation to dryness will result in decomposition of solid substances