Ceutics TEST 2 - Lecture 1

What is the most important characteristic in dissolution rate?

Decreasing particle size and (thus) increasing surface area INCREASES dissolution rate (at a given temp)

Why does viscosity affect dissolution?

Dissolution dependent on agitation. Inc viscosity -> dec. agitation

What is SBEBCD?

sulpho-butyl-ether-beta-cyclodextrin

What are the 5 most common solvents (USP or NF)

Alcohol USP (ethanol) Diluted Alcohol NF Glycerin USP Propylene Glycol USP Purified Water USP

What is Sporanox (itraconazole)?

Antifungal w/ HPBCD

Epivir--Purpose of methyl/propyl paraben

Antimicrobial/preservative

Abilify--Brand name? For?

Aripiprazole, treatment of schizophrenia

Which is more soluble---straight chain carbons or branched?

Branched

What are the most common non-polar solvents?

Carbon tetrachloride Benzene Mineral Oil

How does particle shape affect dissolution?

Total surface area

(T/F) Potable water (tap water) has ions and bacteria which could degrade a drug

True

T/F According to the graph on slide 21, the fine and coarse particle lines will eventually reach the same point (final dissolution), but the coarse particles will take much longer to reach that point - 150 micron (fine); 710 micron (coarse)

True

T/F According to the previous graph, the coarse surfactant line will reach the same point of total dissolution as the fine particles and coarse particles (and maybe a tad higher) a bit faster than the coarse particles alone

True

T/F Coarse particles will dissolve at a faster rate with surfactant than without

True

T/F The faster you stir a solution, the faster the dissolution

True

T/F The higher the amount of drug already in the solution, the harder it is for the rest of the drug to be dissolved

True

(T/F) Rate of dissolution may influence therapeutic response and blood levels

True - the drug may take a very long time to dissolve, it could pass through GI before it dissolves and even gets the chance to work Do fine particles have a higher solubility than coarse particles? : NO--particle size affects RATE not EXTENT

Is alcohol miscible with glycerin, propylene glycol, and water?

Yes

Do monovalent ions dissolve easily?

Yes, solute-solute forces easily overcome

Valium Injection-- purpose of benzoate/benzoic acid

preservative

What is HPBCD?

hydroxy-propyl-beta-cyclodextrin

Define solute

the substance dissolved (small quantities)

What are the units of solubility?

1 gram in X ml (solvent)

What are the 6 factors that influence the dissolution process?

1. Free surface energy (surfactant) 2. Shape of particles (surface area) 3. Temperature 4. Agitation 5. Amount already in solution 6. Viscosity, volume of solvent

How do polar solvents work?

1. HIGH dielectric constant (water dielectric = 78 - this is high) 2. Acid/base reactions break covalent bonds 3. Dipole-dipole interactions

What two factors influence dissolution rate?

1. Particle size 2. Agitation

What are the three types of polarity?

1. Polar 2. Semi-polar 3. Non-polar

Soluble? Nitrates, nitrites, chlorates, lactates

generally

Valium Injection--purpose of benzyl alcohol

1. anesthetic 2. preservative 3. Not a co-solvent (would be >5% as a cosolvent)

What is the dried ion content in 100mL of tap water?

100mg dried solid/100mL

Define solution

2 or more substances forming a HOMOGENEOUS molecular dispersion in a ONE phase system

Epivir--Sparingly soluble =

30-100 parts solvent per 1 part drug

General rule- how many carbons can 1 polar functional group solubilize?

5 carbons/polar group

What is diluted alcohol?

50/50 mix of water and alcohol (50mL H2O and 50mL ethanol = 97mL of diluted alcohol NF)

How many glucose/purinose units are in Beta-cyclodextrin?

7

What is USP pure for alcohol?

94.9-96% v/v at 15.6 ºC

What is the dried ion content in 100mL of purified water?

<1mg dried solid/100mL

What characterizes a saturated solution?

A solution at a given temperature that has dissolved the maximum amount of solute

What are the SPECIFIC LIMITATIONS on OTC products with alcohol in them?

Children < 6 yrs old, <0.5% limit Children 6-12 yrs old, 5% limit Children >12, 10% limit

What is glycerin?

Clear, syrupy liquid with preservative qualities, used in internal products, and is miscible with alcohol and propylene glycol

Define solubility

Concentration of a solute in a saturated solution at a given temperature

According to the Noyes-Whitney Equation (dC/dt = KS(Cs- Ct)), what does Cs and Ct represent?

Cs = concentration of saturated solution in the stagnant layer Ct = concentration in bulk dissolution medium at time t (increases with time) *Note* if Ct << Cs (When Ct is less than 20% of Cs), then omit Ct - then Noyes-Whitney Equation becomes dC/dt = KSCs

What are cyclodextrins?

Cycle oligosaccharide derived from starch w/ alpha D glucose purinose units.

How does increasing molecular weight affect solubility?

Decreases solubility

What is the definition of isomers?

Different drug substances that have the same molecular formula, but the atoms are attached to one another differently (different structural or spacial arrangements) - because of this they have different physical/chemical properties

What is it called when you have increased dissolution due to increased amount of solvent?

Dilution effect - if there is a very large volume of solvent you get a greater concentration gradient

According to the Noyes-Whitney Equation (dC/dt = KS(Cs- Ct)), what does K represent?

Dissolution rate constant = K = D/h (D=diffusion coefficient of solute in solution) - constant for fixed solute/solvent solution (h=thickness of diffusion layer/stagnant layer)

Sulfates? Sulfites? Thiosulfates? Are they soluble?

generally

Primary use of non-polar solvents?

Emulsions and creams (disperse phase)

Is the dissolution process exothermic or endothermic?

Endothermic--INC. temp --> INC. solubility rate of dissolution

What happens in a supersaturated solution?

Excess solute will crystallize out of the unstable solution

There are specifications for ion content in water - certain decreasing ion content is done with which 4 ways?

Filtration Distillation Reverse osmosis Ion exchange

What is the best method for choosing a solvent?

Finding a structurally similar solvent increases solubility

How do surfactants affect solubility?

Form miscelles which help solubilzation

What are co-solvents?

Increase aqueous Solubility by increasing solution stability for weak electrolytes and non-polar molecules

How does free surface energy affect the dissolution process?

Increase free surface energy/surfactant = speed up dissolution (Added note- Tween 80 is a common surfactant)

How does temperature affect the dissolution process?

Increase temperature (Endothermic) = increase rate of dissolution (most drugs do this)

How does viscosity affect the dissolution rate?

Increase viscosity = DECREASE dissolution rate

Are antifungals generally water soluble?

NO--poorly soluble

Is benzyl alcohol at 1.5% used as a cosolvent?

No, only at >5% concentrations

Does itraconazole alone have good solubility?

No--antifungals typically don't - that is why they need a cyclodextrin which is used in Sporanox

Is aripiprazole water soluble?

No--practically insoluble, dependant on pH (more soluble in acidic solutions)

Do non-polar solvents break bonds?

No. Relies on VDW interactions

What is dehydrated alcohol?

Not less than 99.5% ethanol - use when in need of a water free solvent

Are multivalent cations/anions easily soluble?

Not necessarily as the solute-solute interactions may be greater than solute-solvent

Can we absorb solid drugs?

Not until they pass into solution

What are some examples of co-solvents?

Propylene glycol polyethylene glycol (PEG) glycerin alcohol

How does solvent volume affect dissolution?

Related to concentration of solute. High solvent volume = low solute concentration -> concentration gradient favors dissolution

Why is testosterone in a non-polar solvent?

Steroids tend to be hydrophobic

What is used to change free surface energy?

Surfactant

How does the shape of the particle affect the dissolution process?

The key is surface area- Fine particles (HIGH surface area) = higher dissolution rate Coarse particles (lower surface area) = slower dissolution rate

If you increase aggitation, you increase the rate of dissolution - what is happening to the stagnant layer (h)?

The stagnant layer is getting SMALLER - the drug has less distance to travel before getting into the bulk solution

What are the primary characteristics of complexing agents?

They are used to trap molecules. Interiors = hydrophobic, Exteriors = hyrdophillic

Where are solubilities of medical agents listed?

USP, Merck

What is one method of increasing solubility of an insoluble salt?

Using the acid salt tends to increase solubility

What is propylene glycol?

Viscous liquid, misclible with water, ethanol, interchangeable with glycerin, also has preservative properties

Abilify--Co-solvent?

glycerin, propylene glycol

Epivir--Purpose of citric acid and sodium citrate

buffer - important for chemcial stability of drug

Abilify--Purpose of Disodium Edetate

chelating agent/antioxidant

Valium Injection--purpose of alcohol

co-solvent

Valium Injection--purpose of propylene glycol

co-solvent

Abilify--Preservatives?

dl-lactic acid, methyl/propyl paraben

Abilify--Sweetners/flavoring?

fructose, sucrose

What are units of % w/w?

g solute / 100 g solution

What are units of %w/v?

g solute / 100 ml solution

Phosphates, carbonates, silicates, borates, and hypocholorites are usually water_____

insoluble

Sulfide solubility?

insoluble, generally

What about hydroxides and oxides? Are they soluble?

insoluble, generally

Characteristics of non-polar solvents

low dielectric constant.

Define solvent

medium or vehicle for the solute

How do semi-polar solvents work?

mid-level di-electric constant induces polarity in non-polar solvents. Typically used as co-solvents

What are units of % v/v?

ml solute/ 100 ml solution

Epivir--Purpose of sucrose

sweetener

What makes Abilify water soluble?

use of cyclodextrin

Are salts from Na, K, Li generally soluble?

yes

Are salts of alkali metals soluble?

yes

Are the ammonium salts soluble?

yes

Are these generally soluble? NaCl, LiBr, KI

yes

Epivir--is there water present?

yes, aqueous

Epivir--Is it crystalline?

yes, has a specific melting point