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Pharmaceutics > 3 Solubilization > Flashcards

3 Solubilization Flashcards

1
Q

What is the relationship between heat of solution and solubility?

A

A positive heat of solution has a net effect of absorbing heat and an increase of solubility with an increase in temperature.
Negative heat of solution (calcium citrate) shows decreased solubility with an increase in temperature.

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2
Q

What are some factors that affect solubility?

A

Temperature, pH of the solution and physiochemical properties of the solute and solvent

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3
Q

What are the 4 rules of water soluble inorganic molecules?

A 
The compound is soluble if:
Both cation and anion are monovalent
One of the ions in the salt is monovalent.
Salts of alkali metals and ammonia.
Nitrates, sulfates and halides
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4
Q

What is the inorganic molecule with limited water solubility?

A

If both anion and cation are multivalent.

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5
Q

What are the 2 rules for water insoluble inorganic molecules?

A

Hydroxides and oxides are not water soluble.

Phosphates, carbonates, silicates and borates are insoluble.

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6
Q

What are the 3 rules of water solubility for organic molecules?

A

Molecules having one polar functional group is usually soluble to chain lengths of 5 carbons.
Molecules with branched chains are more soluble than the straight chain compound.
Solubility decreases as molecular weight increases

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7
Q

What determines how much drug is available for absorption?

A

The dose, its solubility and dissolution rate.

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8
Q

Why is water solubility desirable for liquid dose form?

A

So the dose of the drug will be a reasonable volume.

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9
Q

What dose form would good if reduced solubility was desired?

A

Suspension. Provided that bioavailability is not affected.

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10
Q

When is a drug considered highly soluble according to the BCS?

A

When the highest dose strength is soluble in 90%.

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11
Q

What are class I drugs?

A

Not many problems.

Dissolution rate must be >85% in 15 minutes

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12
Q

What are class II drugs?

A

The rate limiting step for bioavailability is solubility/dissolution.

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13
Q

What are class III drugs?

A

The rate limiting step for bioavailability is crossing biological membranes.

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14
Q

What are class IV drugs?

A

Present many problems.

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15
Q

What is the Biopharmaceutics Classification System (BCS) for?

A

Oral drug products.

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16
Q

How can the BCS be applied to other dose forms?

A

D:S (dose:solubility) ratio must be

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17
Q

How should we adjust pH to control solubility?

A

Ionizable functional groups may be managed this way.
Usually formulate to a pH of 4-8 for biocompatibility.
Ionized form is water soluble, unionized state is insoluble.
Use Henderson-Hasselbach equation.

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18
Q

What determines the extent of ionization of a drug?

A

The pH of the medium and the pKa of the drug.

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19
Q

What is the pH of maximum solubility?

A

The pH at which precipitation occurs.

Target pH for formulation will be +/- pH unit from pH for maximum solubility.

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20
Q

What are the solubility equations for acidic and basic compounds?

A

Acidic: S=S0 [1+10^(pH-pKa)]
Basic: S=S0 [1+10^(pKa-pH)]
S0 is solubility of unionized form

21
Q

What are the most commonly used buffer components in parenteral products?

A

Citric acid, acetic acid and phosphoric acid.

22
Q

What is a salt?

A

The product of an ionizable drug with an ionizable counter-ion of opposite charge.
Good way to overcome some undesirable properties of a parent drug.

23
Q

When is the use of a salt desirable?

A

To decrease solubility for sustained release products or to help with stability or masking an unpleasant taste.

24
Q

What should we think about for counter ion selection?

A

The pKa of the conjugate base should be greater than the conjugate acid.
Difference of 3 or more pKa units.
Polymorphism.

25
Q

What is the equation for equilibrium constant?

A

K=(A+)(B-)/(AB)

26
Q

How might the common ion effect affect solubility?

A

It may suppress it.
Ex: The hydrochloride salt of a drug may be quite soluble but if given orally, the HCl in the gastric fluid may suppress solubility, dissolution and ultimately bioavailability

27
Q

When is solubility product constant (Ksp)?

A

For a saturated solution or a salt with limited solubility.

28
Q

What is the equation for Ksp?

A

Ksp=(A+)(B-)

As the counter ion (B-) increases, the concentration of drug (A+) in solution is constant.

29
Q

How would hydroscopicity affect stability and how can we fix this?

A

It would decrease stability. We can offset this by making the salt with increased solubility.
Ex: Ketorolac

30
Q

What is solubility from the salt form due to?

A

pH effects, but mostly interactions between drug, counter-ion and solvent.

31
Q

How does the dissolution rate of a salt compare to the parent drug?

A

The dissolution rate of the salt is usually faster because the salt can act as its own buffer in the diffusion layer (independent of bulk pH of medium used).
Implication on bioavailability parameters

32
Q

How is the pharmacology of a parent drug affected when it is made as a salt? What about the counter ions?

A

It may be unchanged but some counter ions may have toxicity if they have pharmacologic activity.
Ex: Lithium, aluminum, bromide, iodide and salicylates

33
Q

How can cosolvents be used? Examples?

A

Can be used in parenteral drug products with limited water solubility.
Ex: Glycerin, alcohol, propylene glycol and polyethylene glycol

34
Q

How do cosolvents do?

A

They provide exponential increases in solubility and allow reduction of water content for products that are susceptible to hydrolysis.

35
Q

What two components are extremely toxic?

A

Ethylene glycol and methanol

36
Q

How is cosolvent selection made?

A

Based upon experimentation.
There will be a logarithmic increase in solubility with increasing volume fraction of cosolvent
Solubility increases for individual cosolvents are additive.

37
Q

What are semi-polar solvents?

A

Alcohol.

May induce a degree of polarity in non polar molecules and improve their water solubility

38
Q

What is dielectric constant?

A

A measure of the effect of the solvent on the potential energy of interaction between two charges or a measure of how effective the material is as an electrical insulator.
No units.

39
Q

What is interfacial tension?

A

The measure of the cohesive forces at the solute-solvent interface.
Polar>50, semi-polar 10-50 and non-polar

40
Q

How do we find the dielectric constant of a solvent mixture?

A

By multiplying the volume fraction for each solvent by its respective dielectric constant and summing.

41
Q

What products contain cosolvents?

A

Opthalamic products rarely contain cosolvents.
Otic preparations may contain glycerin, polyethylene glycol (PEG) and propylene glycol.
Parenterals rarely contain anything higher than 10% ethanol, 40% propylene glycol and 50% PEG.

42
Q

What are some problems with cosolvents?

A

Dilution of a product prepared with cosolvents may result in the drug coming out of solution.
May be a cause for phlebitis if given IV and muscle damage if given intramuscularly,

43
Q

How will cosolvents affect reaction rates?

A

By shifting the equilibrium between reactants and the transition state.
If the transition state is more polar (ionized) than the reactants, increasing the polarity of the solvent will increase reaction rates.

44
Q

What are surfactants?

A

Molecules with polar and non-polar regions.
Can be used in parenteral dose forms.
Non-polar region usually hydrocarbons, polar region can be anionic (carboxylate), cationic (ammonium) or non-ionic (PEG, sugar).

45
Q

When are micelles formed?

A

As the concentration of surfactant increases. The concentration at which these begin to form is the critical micelle concentration (CMC).

46
Q

Which surfactants are used in parenteral products?

A

Tween-80 and Cremophor EL

Can cause extreme irritation , damage to tissues and systemic toxicity in children and newborns, thus practical limits.

47
Q

What do complexing agents do?

A

Involve incorporating drug within the complexing agent so that outer hydrophilic groups of the agent interact with water and make the whole complex soluble.
Ex: Caffeine-benzoic acid mixture, amphotericin-B complex with sodium cholesteryl sulfate (lipid complex)

48
Q

What are cyclodextrins?

A

Molecules composed of 6,7 or 8 glucopyranoside units joined through 1-4 bonds.
The interior is lipophilic while the exterior is hydrophilic due to hydroxyl groups.
A lipid-soluble drug can complex with the interior and the whole complex will be water soluble.

49
Q

How would we find the amount of a salt form needed to prepare a solution?

A

Take the molecular weights of the drug and the salt form.

Divide one by the other so you find how much 1 g of drug equals in salt form.

Pharmaceutics (4 decks)

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