Solubility and Distribution Phenomena, Slides of Pharmacy

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2/22/2019 1

Solubility and distribution phenomena

Interfacial phenomena

Complexation and Protein Binding

Colloids

Rheology

Kinetics

Micromeritics

Pharmaceutical polymers

Solubility and distribution

Dr. Ghaidaa S. Hameed

Physical pharmacy II

2/22/2019 2

• Solubility is defined in quantitative terms as the

concentration of solute in a saturated solution at a certain temperature, and in a qualitative way , it can be defined as the spontaneous interaction of two or more substances to form a homogeneous molecular dispersion.

• An unsaturated or subsaturated solution is one containing the

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

• A supersaturated solution is one that contains more of the

dissolved solute than it would normally contain at a definite temperature, were the undissolved solute present.

Solubility Expressions

• The solubility of a drug may be expressed in a

number of ways. The United States

Pharmacopeia ( USP ) describes the solubility of

drugs as parts of solvent required for one part

solute. Solubility is also quantitatively

expressed in terms of molality, molarity, and

percentage. The USP describes solubility using

the seven groups listed in Table 9-1.

Solvent–Solute Interactions

The pharmacist knows that water is a good

solvent for salts, sugars, and similar

compounds, whereas mineral oil is often a

solvent for substances that are normally only

slightly soluble in water. These empirical

findings are summarized in the statement, “like

dissolves like “.

H.W : Why water acts as a good solvents?

Polar Solvents

1) Polarity of the solvent, that is, to its dipole moment.

Polar solvents dissolve ionic solutes and other polar

substances.

2) The ability of the solute to form hydrogen bonds is a

far more significant factor than is the polarity as

reflected in a high dipole moment. Water dissolves

phenols, alcohols, aldehydes, ketones, amines, and

other oxygen- and nitrogen-containing compounds.

3) Difference in acidic and basic character of the

constituents in the Lewis electron donor–acceptor

sense also contributes to specific interactions in

solutions.

4. Depends on structural features such as the ratio of the polar to the

nonpolar groups of the molecule. As the length of a nonpolar chain of an

aliphatic alcohol increases, the solubility of the compound in water

decreases. Straight-chain monohydroxy alcohols, aldehydes, ketones, and

acids with more than four or five carbons cannot enter into the hydrogen-

bonded structure of water and hence are only slightly soluble. When

additional polar groups are present in the molecule, as found in propylene

glycol, glycerin, and tartaric acid, water solubility increases greatly.

5) Branching of the carbon chain reduces the nonpolar effect and leads to

increased water solubility. Tertiary butyl alcohol is miscible in all

proportions with water, whereas n-butyl alcohol dissolves to the extent of

about 8 g/100 mL of water at 20°C.

Non-polar Solvents

• Nonpolar compounds, however, can dissolve nonpolar

solutes with similar internal pressures through

induced dipole interactions. The solute molecules are

kept in solution by the weak van der Waals–London

type of forces. Thus, oils and fats dissolve in carbon

tetrachloride, benzene, and mineral oil. Alkaloidal

bases and fatty acids also dissolve in nonpolar

solvents.

Solubility of Liquids in Liquid

• Frequently two or more liquids are mixed together in

the preparation of pharmaceutical solutions. For

example, alcohol is added to water to form

hydroalcoholic solutions of various concentrations;

volatile oils are mixed with water to form dilute

solutions known as aromatic waters; volatile oils are

added to alcohol to yield spirits; ether and alcohol are

combined in collodions; and various fixed oils are

blended into lotions, sprays, and medicated oils.

• Liquid–liquid systems can be divided into two

categories according to the solubility of the

substances in one another: (a) complete

miscibility and (b) partial miscibility. The

term miscibility refers to the mutual

solubilities of the components in liquid–liquid

systems.

Solubility of Solids in Liquids

• Systems of solids in liquids include the most frequently encountered and

probably the most important type of pharmaceutical solutions. Many

important drugs belong to the class of weak acids and bases. They react

with strong acids and bases and, within definite ranges of pH, exist as ions

that are ordinarily soluble in water.

• Although carboxylic acids containing more than five carbons are relatively

insoluble in water, they react with dilute sodium hydroxide, carbonates, and

bicarbonates to form soluble salts. The fatty acids containing more than 10

carbon atoms form soluble soaps with the alkali metals and insoluble soaps

with other metal ions. They are soluble in solvents having low dielectric

constants; for example, oleic acid (C17H33COOH) is insoluble in water but is

soluble in alcohol and in ether

• Hydroxy acids, such as tartaric and citric acids, are quite soluble in water because they are solvated through their hydroxyl groups.
• Many organic compounds containing a basic nitrogen atom in the molecule are important in pharmacy. These include the alkaloids, sympathomimetic amines, antihistamines, local anesthetics, and others
• The aliphatic nitrogen of the sulfonamides is sufficiently negative so that these drugs act as slightly soluble weak acids rather than as bases. They form water-soluble salts in alkaline solution by the following mechanism. The oxygens of the sulfonyl (—SO 2 —) group withdraw electrons, and the resulting electron deficiency of the sulfur atom results in the electrons of the N:H bond being held more closely to the nitrogen atom. The hydrogen therefore is bound less firmly, and, in alkaline solution, the soluble sulfonamide anion is readily formed.