medicine formulations 1 Wk5

Why is solubility important in the pharmaceutical industry?

Solubility determines drug absorption, affects dosage form design, limits drug candidates, and impacts IV injections and oral solid dosage forms.

Define "solution" and "solubility."

A solution is a homogenous mixture of two or more components. Solubility is the concentration of a saturated solution under defined conditions.

What are the typical components of a solution?

Solute (the substance being dissolved) and solvent (the substance doing the dissolving, determining the phase of the solution).

What are the different types of solutions (based on phases involved)?

Solids in solids, liquids in liquids, gases in liquids, and solids in liquids.

Describe the states of saturation in a solution.

Unsaturated (more solute can dissolve), saturated (dynamic equilibrium between dissolution and precipitation), and supersaturated (contains more dissolved solute than normally possible; unstable).

What is "intrinsic solubility" (S0)?

The solubility of the neutral, unionized form of a material at a given temperature and pressure.

How does temperature generally affect the solubility of solids in liquids?

Solubility usually increases with temperature (endothermic dissolution), but can decrease if dissolution is exothermic.

Explain the concept of "like dissolves like" in terms of solvent polarity.

Polar solvents dissolve polar solutes (and ionic compounds), while nonpolar solvents dissolve nonpolar solutes.

What is the role of semi-polar solvents?

Have an intermediate degree of polarity, enter into induced dipole interactions.

Why is water a good solvent?

High dielectric constant (reduces attraction between ions), breaks covalent bonds (for potential strong electrolytes), and engages in dipole bonding (hydrogen bonding).

How do molecular structure and crystal characteristics affect solubility of solids in liquids?

Certain functional groups and crystal structures can increase or decrease solubility. Solubility can be impacted by different polymorphs.

How does pH affect the solubility of weak acids and weak bases?

Solubility of weak bases decreases with increasing pH, while solubility of weak acids increases with increasing pH.

Define cosolvents and give examples.

Liquids added to a solvent to increase the solubility of poorly soluble drugs (e.g., alcohol, glycerol).

Explain "salting out."

The decrease in solubility of a non-electrolyte in a solution when a salt is added to the solution.

State Henry's Law and its application.

Conc = σ (solubility coefficient) x P. Used to determine the solubility of gas in liquids.

What are different ways to express concentration quantitatively?

Molality (moles/kg), molarity (moles/L), percentage (% w/w, % v/v, % w/v), quantity per quantity (e.g., g/L), and mole fraction.

Define Molality.

Moles of solute per kg of solvent.

Define Molarity.

Moles of solute per liter of solution.

What is the definition of percentage concentrations (% w/w, % v/v, % w/v)?

Parts of solute in parts of solution: For solids in liquids: # parts by weight (g) in # parts by volume of solution (mL). For liquids in liquids: # parts by volume (mL) in # parts by volume of solution (mL). For gases in liquids: # parts by weight (g) in # parts by volume of solution (mL).

What is a mole fraction?

Moles of a particular component divided by the total number of moles in the solution.

How does the pharmacopoeia describe solubility quantitatively?

Descriptive terms are used (e.g., very soluble, freely soluble, sparingly soluble, slightly soluble, very slightly soluble, practically insoluble).

What factors complicate predicting the solubility of solids in liquids?

Temperature, solute-solute intermolecular forces (related to melting point), and molar heat of fusion.

What is "ideal solubility," and what equation predicts it?

Estimated solubility based on solute properties, neglecting solvent effects:

−log⁡X=ΔHf2.303R[T0−TmT0×Tm]−logX=2.303RΔHf[T0×TmT0−Tm]

where X is the mole fraction solubility, ΔH_f is the molar heat of fusion, R is the ideal gas constant, T_m is the melting point, and T_0 is the experimental temperature.

What are the assumptions made when using the ideal solubility equation?

Experimental temperature is much lower than the melting point, solubility is very small (works best for drugs), independent of the solvent, and dissolved in very polar solvents (e.g., water).

What is "miscibility?"

The ability of liquids to mix in all proportions.

What is "partial miscibility?"

When liquids mix only in certain proportions or at certain temperatures.

What are "electrolytes," and why are most drugs considered weak electrolytes?

Electrolytes dissociate into ions in solution. Most drugs have ionizable groups and behave as weak acids or bases.

Write the Henderson-Hasselbalch equations for weak acids and weak bases.

For weak acids: pH = pKa + log ([A-]/[HA])

For weak bases: pH = pKa + log ([B]/[BH+])

How can the Henderson-Hasselbalch equations be used to calculate the total solubility (S) of a weak acid or weak base?

S = S0 + [A-] for weak acids and S = S0 + [BH+] for weak bases, where S0 is the intrinsic solubility.

How can you identify an acid from base?

Weak acids bond with positive ions and weak bases bond with negative ions.

What is the typical pKa range for weak acids and weak bases?

Weak acids usually have pKa from 3-7, weak bases usually have pKa from 7-11.

Define intrinsic solubility.

The solubility of the undissociated species (at a pH for which all the drug molecules are neutral).

What does the value of the partition coefficient (K) tell you about a drug's properties?

It indicates whether a drug is lipophilic (K >> 1) or hydrophilic (K << 1).

Why is octanol often used as the "oil" phase in partition coefficient measurements?

Octanol is a good mimic of the lipid environment of biological membranes.

Why is Log P often used instead of P?

Log P values are more convenient for expressing a wide range of partition coefficient values.

How do Log P values relate to a drug's ability to cross biological membranes and its solubility in GI fluids?

High Log P (>1) indicates poor solubility in GI fluids but good ability to cross intestinal bilayers. Low Log P (<1) indicates good solubility in GI fluids but difficulty in crossing the intestinal bilayer.