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what is solution

A solution is a homogeneous one-phase system consisting of two or more components.
Solvent: Phase in which the dispersion occurs
Solute: Component which is dispersed as small molecules or ions in the solvent

Types of solutions: aqueous or non-aqueous


concentration of solute

concentration is usually well below its saturation solubility in order to avoid the possibility of drug ppt out of the solvent as a result of temperature changes during storage and use


advantage of soluton

• the drug is already dissolved in the solvent system, hence DRUG ACTION CAN BE RAPID, allowing their use in emergencies, e.g. the use of adrenaline solution, as an injection, for the treatment of anaphylaxis

• when drug absorption is required prior to drug action, for example, following oral administration, the drug in a solution is already in a molecular form and thus, AVAILABLE FOR ABSORPTION

• solutions provide DOSE UNIFORMITY, and specific volumes of the liquid solutions that can be measured accurately; this allows a range of different doses to be easily administered

• oral solutions are EASILY SWALLOWED and are beneficial for patients for whom swallowing may be difficult, e.g. children and older people.

• solutions are EASIER TO MANUFACTURE compared to other dosage forms.


Disadvantage of solution

• many drugs are inherently UNSTABLE, and instability is increased when a drug is present in solution, i.e. as molecules. The solution formulation is therefore not feasible for certain drugs. For other drugs, stability can be enhanced by optimizing the formulation

• many drugs are POORLY SOLUBLE in water. Their formulation as a solution is CHALLENGING

• liquids are BULKY and less easy for the patient to carry, for example, the daily dose, compared to solid dosage forms. Liquids are also more EXPENSIVE to TRANSPORT , which increases the medicine’s cost. The packaging of pharmaceutical solutions requires materials of higher quality


Types of solutions:

aqueous or non-aqueous


Aqueous solution

Water is the most widely used solvent for aqueous solutions.

The quality of water required depends on the type of preparations to be made
a)Potable water
b)Purified water BP
c)Water for Injection BP
d)Water free from carbon dioxide or air


portable water

for oral/external solution that are not intended to be sterile

normally not used for the manufacture of solution or extemporaneous compounding as it contains dissolved substances which could interfere with the formulation, for example, reduce drug solubility and stability.


purified water

to prepare non-parenteral solution

purified from tap water by distillation, ion exchange or reverse osmosis.


water for injection BP

purified from purified water to remove pyrogen


most drug are not completely dissolved at normal storage temperature
various methods employed to increase apparent solubility includes

Chemical modification
Particle size control



used to increase water solubility of drugs which do not contain ionizable group(s) and whose solubility can thus not be increase by ph adjustment.

The solubility of a weak electrolyte or non-polar compound in water can be improved by the addition of a water-miscible solvent in which the compound is also soluble.
Vehicles used in combination to increase the solubility of a drug are called cosolvents.
The solubility of a drug is generally affected by the dielectric constant of the solvent system.

Ideally,suitable blends should possess values of dielectric constant between 25 and 80.
The choice of suitable cosolvents is limited for pharmaceutical use.
Examples: Co-trimoxazole+Propyleneglycol+Water Paracetamol + Alcohol + Propylene glycol + Syrup Betamethasone valerate+Isopropanol+Water


typically a linear increase in cosolvent fraction results in log increase in drug solubility

typically a linear increase in cosolvent fraction results in log increase in drug solubility


non-polar drug are poorly soluble in water.
cosolvency do what ?

need to lower polarity by adding liquid eg water-miscible organic liquid with a low polarity.


pH control

If a drug is either a weak acid or a weak base, its degree of ionization and consequently its solubility are influenced by the pH of the solution.
This is expressed by the Henderson-Hasselbalch equation.
In controlling the solubility of a drug in this way, it must be ensured that the chosen pH does not conflict with other product requirements.

weak acid are ionized when ph increase
weak base are ionized when ph decrease



The solubility of a drug in water can be improved by the addition of a surfactant.
The concentration of surfactant used should be above its critical micellar concentration -->micellarsolubilization However,a large excess of surfactant is undesirable. Hydrophilic surfactants with HLB values above 15 are useful solubilizing agents.


Factors that affect the choice of solubilizing agents:

Toxicity and irritancy
Miscibility with solvent system
Compatibility with other components
Odour and taste

Fat-soluble vitamins+Polysorbates
Iodine+Macrogol ethers
Steroids+Polyoxyethylated castoroil Cresol+chloroxylenol+potassium soaps of fatty acids

A combination of cosolvent and solubilizing agent may be employed to improve solubility
VitaminA+Polysorbate80+Glycerol Chloroxylenol+Potassium ricinoleate+ethanol+ terpineol

the amount of surfactant used should not be excessive due to its potentially harmful effects


determination of minimum concentration of surfactant for solubilization of drug

A series of vials, each consisting of the solvent with a constant concentration of the surfactant is prepared.
Different amounts of the drug are added to the vials and the optical density of the mixtures determined.
The maximum drug concentration(MDC) that produces a clear solution is obtained from the graph.

Using the same procedure, the MDC values of different concentration of the surfactant are determined
A plot of MDC vs surfactant concentration is constructed
The minimum surfactant concentration can be determined from this plot.



this involves the interaction of a poorly soluble drug with a soluble material to form a soluble complex.

complex formation should be easily reversible as most complexes are macromolecules which tend to be inactive

iodine + PVP
salicyclates + xanthines




for complexation
Cyclodextrins (CDs) are non-reducing cyclic glucosebased oligosaccharides, comprising a variable number of D-glucose residues linked by α-(1,4) glycosidic linkages. The three most important CDs are alpha, beta and gamma cyclodextrins which consist o 6, 7 and 8 D-glucopyranosyl units, respectively, arranged in a ring. Three-dimensionally, CDs can be visualized as a hollow truncated cone.
The interior cavity of cyclodextrins is apolar, while their exterior is hydrophilic.
The hydrophilic exterior results in CDs being soluble in water. Concurrently, the less polar interior can accommodate non-polar drug molecules via non-covalent interactions, thereby allowing the nonpolar drug to be ‘hidden’, enabling it to be molecularly dispersed in water. Thus, drug inclusion within CDs effectively increases their aqueous solubility.

Each cyclodextrin molecule can form complexes with one or more drug molecules. Drug-CD complexes can also self-associate, and the water-soluble structures formed can further solubilize the drug through non-inclusion complexation. Upon administration, for example orally, of a solution containing a drug-CD complex, the drug can be released from the CD molecule and the free drug can then be absorbed through the gastrointestinal tract.


Chemical modification

This involves synthesis of soluble salts of the drug.
The soluble salt which may not have any activity is converted back to the active base in the biological system.
Sodium phosphate salts of hydrocortisone, prednisolone and betamethasone
Sodium succinate salt of chloramphenicol


particle size reduction

The size and shape of very small particles (<1 micron) can affect their solubility.

particle size is commonly reduced by milling.

this method is less commonly employed to improved solubility.


Non aqueous solution

The solvents used are non-aqueous in property.

they are employed for various reasons:
1) to prepare solutions of drugs which are unstable in water
2) to prepare intramuscular injections of drugs for depot therapy.

The solvents are classified as fixed oil of vegetable origin, alcohol, polyhydric alcohols, mineral oils and other.


Fixed oils of vegetable origin

E.g. almond oil, arachis oil, olive oil, corn oil, soya oil, castor oil, cottonseed oil, sesame oil, coconut oil.

Used in the formulation of injections, eye-drops, liniments and oral preparations.

Oily Phenol Injection BP (almond oil)
Dimercaprol Injection BP (arachis oil)
Methyl Salicylate Liniment BP (arachis oil) Physostigmine Oily Eye-drops BP (castor oil)

Tasteless and odourless fixed oils are used for oral preparations.
Fractionated coconut oil is used as a solvent for phenoxymethylpenicillin


what are fixed oils of vegetable origin typically used for

Used in the formulation of injections, eye-drops, liniments and oral preparations.



For internal and external use.
More commonly employed in low concentration, as a cosolvent with water in the formulation of aqueous solutions for oral and parenteral use.

Industrial methylated spirit
Ethanol with 5% methanol as a denaturant
For external use.
For external use


Polyhydric alcohols

Commonly used as a cosolvent with water in the formulation of injections.

For internal and external use.
E.g. Phenol Ear Drops BPC 1973

Propylene glycol
For internal and external use (include otic soln)
E.g. Digoxin Injection BP, Phenobarbitone Injection BP, Chloramphenicol Ear Drops BP

Polyethylene glycols of low molecular weight
For internal and external use.
E.g. Erythromycin Ethylsuccinate Injection BP

Dipropylene glycol, diethylene glycol, ethylene glycol Used in the formulation of external preparations for veterinary and horticultural use.


Mineral oils

Liquid paraffin
For internal and external use.

Limited use as a solvent in pharmaceutical preparations because of its oily and tacky nature.
Vegetable oils are generally preferred.

More often employed in the formulation of emulsions.


Not for internal use

Common solvent for ear drops

Ethyl ether
Cosolvent with alcohol in some collodions
More commonly used for extraction of crude drugs

Isopropyl myristate, isopropyl palmitate
More commonly used in cosmetics

Dimethylsulphoxide, dimethylformamide, dimethylacetamide
Mainly used in veterinary products

Solvent for insecticides


can prevent [o] by purging soln with N2 and create a N2 headspace within the container.

can prevent [o] by purging soln with N2 and create a N2 headspace within the container.



sweetening agent
flavours and fragrances