Biopharm solutions 1

A preparation that contains one or more dissolved chemical substances in a suitable solvent or mixture of mutually miscible solvents

What is the USP definition of solutions?

• all solutes are uniformly dispersed as individual molecules

• there are NO particles

• drug molecules in a solution are present as individual molecules

• excipient molecules in a solution are present as individual molecules

What is the defining characteristics of a solution?

• cosolvent

• complexing agent

• solubilizing agent

State 3 specific types of excipients that may increase the apparent solubility of another solute in a mixture

• Any sample of any size taken from any part of the container has the same concentration of all solutes as any other sample of any size taken from any other part of the container

• solutes don’t separate from the solvent during storage

• solute don’t separate from each other during storage

Define homogeneous

The highest dissolved concentration that can be prepared in a particular mixture

Definite solubility

A mixture of 2 or more miscible liquids used as a solvent

Define cosolvent system

• Polarity of solvent system

• storage temperature

• pH

State 3 factors that determine solubility of a compound in a liquid

• ethanol

• glycerin

• PEG 300/400

• Propylene glycol

• isopropyl alcohol

• acetone

State 3 examples of solvents that are miscible with water and may be used in oral or topical products

• solutions are homogeneous so no preparation is required before measuring out a dose (no need to shake)

• doses are easily customized (by choosing the volume to administer

• easy to swallow

state 2 advantages of solutions as a dosage form

• chemical degradation reactions occur more quickly in solutions than in solid dosage forms

  • shelf life= shorter

• solutions are heavy and bulky compared to solid dosage forms

  • packing and shipping= higher

state 2 disadvantages of solutions as a dosage form

the concentration of each solute in a solution is less than its solubility in the mixture

Explain the relationship between solute concentration and solute solubility in a solution

the concentration of solutes in most solution products is usually much less than their solubility values to decrease the probability of precipitation due to temp variation

(product may see temp variation, solubility can change, this lowers risk of precipitation)

explain why the concentration of solutes in most solution products is usually much less than their solubility values

• solubility of weak acids increases as pH of the mixtures is increased

• solubility of weak bases decreases as pH of the mixture is increased

explain how pH affects the solubility of weak acids and weak bases.

municipal drinking water/ tap water isn’t acceptable because…

• tap water may contain up to 1 mg/mL of dissolved solutes like Ca2+, Mg2+, SO4 2-, Cu2+

  • these ions can precipitate drugs or other solutes in a drug product

  • divalent cation can catalyze drug degradation reactions

• dissolved organic compounds

Why is purified water usp used instead of municipal tap water in pharmaceutical solutions?

F (solutions and suspensions are different)

A solution is another name for a suspension T/F

T

In a solution, all solutes are present as individual molecules T/F

F (keyword particles, solutions present as molecules)

Solutions contain dispersed particles that may settle during storage. T/F

T

Solubility of a weak acid increases as pH is increased T/F

F (solubility decreases as pH increases)

solubility of a weak base increases as pH is increased T/F

T

Alcohol USP is ~ 95% v/v alcohol T/F

F (topical products only)

isopropyl alcohol may be used in oral and topical products.

T

Accurate dose measurement of a solution requires a calibrated device T/F

• weak base solubility decreases as pH increases

• dissolved concentration may now exceed solubility

• precipitation occurs

A product contains a weak base drug that precipitates after pH is increased. explain the most likely reason

homogenous

a solution is sampled from the top and bottom of the bottle and gives the same concentration in both samples. what property of solutions does this demonstrate

resists change in pH

Define buffer

• buffer resists pH change by small additions of H or OH (which can come from the container or from reactions within the product)

• maintains product pH in a narrow range during storage

• helps protect, solubility/stability

explain how a buffer helps maintain product quality

5.8-7.8

(effective buffer range: pKa-1 to pKa +1)

calculate effective buffer range for pKa= 6.8

2.4-4.4

(effective buffer range: pKa-1 to pKa +1)

Calculate effective buffer range for pKa= 3.4

95 mL alcohol and 5 mL water in every 100 mL

Alcohol USP contains approximately 95% v/v alcohol. How many mL of actual alcohol are present in 100 mL of Alcohol USP?

No, it should be 5% or lower

If an oral product is labeled for children age 6-12, is 7% v/v alcohol within the FDA recommended limit

The solubility of weak bases decrease as pH increases. As a result, the pH 4 should give higher solubility

If a weak base drug has solubility of 10 mg/mL at pH 4 and 1mg/mL at pH 7, which pH gives the higher solubility?