Solutions

In physicochemical terms, solutions can be prepared from any combination of a solid, liquid and/or gas, the
three states of matter. For example, a solid solute is may be dissolved in another solid, a liquid or a gas and
the same being true for a liquid solute and a gas. There are a total of 9 types of homogeneous mixtures possible.

1. Define important terminology in the subject of liquid dosage forms

Solute: the dissolved agent in a solution
Solvent: the component in which the solute dissolves in
Dissolution: the process of a solid going into the solution
Solution: It is a thermodynamically stable, homogeneous system made up of 2 or more components
Pharmaceutical Solution: Liquid preparations that contain one or more substances dissolved in a
suitable solvent. (Can be a mixture of mutually miscible solvents)
Saturated Solution: is a solution which contains the maximum amount of solute that can possibly
dissolve in the given solvent at a given temperature and pressure.
Supersaturated Solution: larger amount of solute in which the solvent can accommodate at a given
temperature and pressure
Drug Solubility: is mL of solvent required to dissolve 1g of the drug
* Solute is present in the smallest amount while the solvent is the larger, liquid component*
* Most pharmaceutical solutions are unsaturated *
*Solutes differ in their solubilities in different solvents and Temperature, Reduction of particle size,
enhancers and agitation can be used to increase dissolution whenever needed*

2. Important Uses of Pharmaceutical Solutions

Solutions can be used as:
1. Vehicles for administration
2. Flavourings, Buffers, Preservatives and suspending agents
3. Test solutions for analysis
4. Dry mixtures
5. Components for extemporaneously prepared products

3. The Dissolution Process

The dissolution process will involve the inter-molecular forces of attractions between solute molecules and solute-solvent interactions.
Step 1: Breaking of solute bonds
Step 2: Separation to provide space in the solvent for the solute
Step 3: Interaction between the solvent and solute molecule and ion.
- is the solute chemically stable in the solvent
- are the two or more solute chemically stable in the solvent
- How is it affected by light, temperature and pH in the solvent
(All these will define how the solution should be prepared, packaged and preserved)
*Hydrophilic dissolves Hydrophilic
*Hydrophobic dissolves Hydrophobic

4. Criteria of a Solvent
There are 3 important criteria a solvent must fulfil:
1) Completely dissolve the drug and its other ingredients at the desired concentration
2) Safe, Non- Toxic

3) Aesthetically Acceptable to patients : Imagine being a patient and ask yourself what is considered aesthetically acceptable to you appearance, taste, smell.

5. Classifications of Solvents (based on)

-

Solute Molecular size (Micromolecular or Macromolecular)

Uses of solution (Oral, Otic, Ophthalmic, Topical)
Composition of solution (Aqueous meaning to say water is the largest component)
Aqueous Solutions can include:
- Syrup
- Aromatic water (solutions of volatile oils)
- Mucilages (Solutions of vegetable gums in water)
- Aqueous Acids (Dilute aqueous solutions of acids (<10%))
- Non Aqueous Solutions (Solvents other than water)

6. Common Pharmaceutical Solvents

1) Water ( Portable Drinking Water, Purified water, Water for injection)
- Purified water is water purified by
1. Filtration through activated carbon beds
2. Addition of chemical additives/water softeners
3. Deionisation and electrodialysis to remove cations and anions
4. Reverse Osmosis, Ultra Filtration and distillation to give purified water of the required specifications such as (size
of particles and no. of particles in the water.

2) Alcohol (Ethyl Alcohol, Ethanol) - miscible with water

- Most useful after water, can be used as solvent, excipient, antimicrobial preservatives
though there are concerns about the toxicity of alcohol (esp for children)
3) Dilute Alcohol [NF]- 41 to 41% wt ( 48 to 49% by vol) of ethanol mixed with water
- Mixture of equal volumes of Alcohol, USP and Purified Water, USP.
4) Rubbing Alcohol ( Ethyl Alcohol / Isopropyl Alchohol)
- Contains about 70% ethyl alcohol (Isopropyl Alcohol) by volume in water, denaturants, colourants, perfume oils and stabilizers
- Used as Germicide, skin cleanser, Externally for bedridden patients (disinfecting solutions)
5) Glycerin USP (Glycerol)
- Clear syrupy
- Sweet Taste
- Miscible in water and alcohol
- Preservative and stabilizer
6) Propylene Glycol (USP)
- Viscous liquid miscible in both water and alcohol.

7. Syrups
Syrup is a concentrated, or nearly saturated solution of sucrose or sucrose substitute in water
- Simple Syrup : Sucrose + Water
- Non- Medicated Syrup (Flavouring Syrup): Pleasant vehicle for therapeutic agents
- Medicinal Syrup: w therapeutic compounds
Other excipients include;
- Sugar (sucrose subt, for viscosity to mask the taste and drug irritation
- Antimicrobial preservatives is a must as sugar tend to have high microbial growth
- Flavourants
- Colourants
- Stabilizers. Etc.
* Compatibility is important
Preparation of Syrups: (4 methods)
1) Solution with heat (Problem with the inversion of sugar due to hydrolysis)
2) Solution with agitation w/o heat
3) Addition of sucrose to a medicated liquid or to a flavoured liquid
4) Percolation: Filtration of a liquid for extraction
Sources of Sweeteners:
1) Sugar
2) Non-sugar Polyols Glycerin, sorbitol, propylene glycol, mannitol
(can provide viscosity also)
3) Non- Nutritive Artificial Sweeteners: Aspartame, Saccharin.
(cannot provide viscosity, thus viscosity adjusters such as Methylcellulose are needed)

8. Elixirs (contains alcohol)

Clear, sweetened hydroalcoholic solutions
Alcoholic content: 5 % 40%
Glycerin can act as preservative.
Preparation of Elixirs:
1) Simple Solution with agitation and/or by admixture or two or more liquid ingredients
- Alcohol soluble and water soluble components are dissolved separately
- Aqueous solution is added to the alcoholic solution
- Alcohol is added to keep all contents in solution
- The addition of aqueous solutions (reducing alcohol concentration) to elixirs may
cause turbidity or separation
Elixirs Vs. Syrups:
E less sweet than S
E less effective than S
They both dissolve both water soluble and alcohol soluble materials
E is more stable and easier to prepare
E is preferred.

9. Spirits
-

Alcoholic / Hydroalcoholic solution of Volatile substances.

Prepared by Maceration (extracting oil from fruits) or distillation
High Alcohol content 60%

10. Tinctures
-

Alcoholic/ Hydroalcoholic solution from Vegetable or Chemical substances

Prepared by Maceration or percolation
High Range of Alcohol Content 15 80%
MUST BE CLOSED TIGHTLY IN LIGHT RESISTANT CONTAINERS.

11. Collodions
-

Liquid preparations containing nitrocellulose pyroxylin in a solvent mixture of alcohol

and ethyl ether
HIGHLY FLAMMABLE
EXTERNAL USE ONLY

12. Liniments
-

Alcoholic/ Oleagineous solutions or emulsions of various substances intended for external applications only.
EXTERNAL USE