Solutions

Question 1

Composition of a solution

Answer 1

Homogenous one-phase system consisting of 2/more components

• Solvent: Phase in which dispersion occurs
• Solute: Component which is dispersed as small mol/ions in the solvent

Types: Aq/Non-aq

Question 2

Advantages of solutions

Answer 2

1) Uniform distribution of drug
2) Easy to swallow (Good for pediatrics & geriatrics)
3) Immediately available for absorption
4) < drug irritation than tablets/capsules

Question 3

Disadvantages of solutions

Answer 3

1) Bulky - Inconvenient to store/transport
(For aq solutions)
2) Poorer stability (esp if drug prone to hydrolysis)
3) Prone to microbial growth/contamination
4) Unpleasant taste of drug more pronounced

Question 4

Types of solutions

Answer 4

1) Aqueous solutions (Most common: H2O as solvent)
- Quality of H2O depends on preparation to be made
(Portable H2O/Purified H2O BP/H2O for injection BP/H2O free from CO2/Air)
- May not be possible to ensure complete dissolution of all ingredients at normal storage temperature
- Methods are employed to increase apparent solubility

2) Non-aq solutions
- Solvents used are non-aq in property

Question 5

List methods to increase apparent solubility of compounds in an aq medium

Answer 5

• Cosolvency
• pH control
• Solubilization
• Complexation
• Chemical modification
• Particle size control

Question 6

How does co-solvency help to increase solubility of compounds in an aq medium?

Answer 6

Cosolvents: Vehicles used in combination to increase the solubility of a drug

How: By addition of a H2O-miscible solvent in which the compound is also stable

• Solubility of drug is affected by the dielectric constant
  (Ideal: Between 25-80*)

Eg.
Co-trimoxazole + Propylene glycol + H2O
Paracetamol + Alcohol + Propylene glycol + Syrup
Betamethasone valerate + Isopropanol + H2O

Question 7

How does pH control help to increase solubility of compounds in an aq medium?

Answer 7

• If drug is weak acid/base, it’s degree of ionisation & consequently its solubility is influenced by the pH of the solution

Note: Ensure that chosen pH does not conflict with other product requirements

Question 8

How does SOLUBILIZATION help to increase solubility of compounds in an aq medium?

Answer 8

How: Adding surfactant

• Use conc above cmc, but large excess undesirable
• Hydrophilic surfactants with HLB values > 15 are useful solubilizing agents

Factors affecting choice:

• Toxicity & irritancy
• Miscibility with solvent system
• Compatibility with other components
• Odour & taste

Eg. Fat-soluble vitamins + polysorbates/
Iodine + macrogol ethers

• Combination of cosolvent & solubilizing agent may be employed to improve solubility
  Eg. Vit A + Polysorbate 80 + Glycerol

Question 9

How much surfactant should be used?

Answer 9

Lowest possible concentration

- Amount of surfactant should not be excessive due to its potentially harmful effects

Question 10

How to determine min [surfactant] to be used for solubilization of drug?

Answer 10

• Prepare a series of vials, each consisting of solvent with a constant [ ] of the surfactant
• Diff amnts of drug are added & the optical density of the mixtures is determined
• -> MDC that produces a clear solution is obtained from the graph
• The MDC values of diff [ ] of the surfactant are determined
• Plot MDC against surfactant concentration

Question 11

How does COMPLEXATION help to increase solubility of compounds in an aq medium?

Answer 11

• Involves interaction of poorly soluble drug with a soluble material to form a soluble complex
• Complex formation should be easily reversible

Eg. iodine + polyvinylpyrrolidone
Salicylates + xanthines

Question 12

How does CHEMICAL MODIFICATION help to increase solubility of compounds in an aq medium?

Answer 12

• Involves synthesis of soluble salts of the drug
• -> Soluble salt which may not have any activity is converted back to active base in the biological system

Eg.
Sodium phosphate salts of hydrocortisone, prednisolone & betamethasone

Question 13

How does PARTICLE SIZE REDUCTION help to increase solubility of compounds in an aq medium?

Answer 13

• Size & shape of very small particles (<1 micron) can affect their solubility
• Particle size commonly reduced by milling
  (Less commonly employed method to improve solubility)

Question 14

What are non-aq solutions employed for?

Answer 14

1) Prepare solutions of drugs that are unstable in H2O

2) Prepare IM inj of drugs for depot therapy

Question 15

Classifications of solvents for Non-Aq Solutions

Answer 15

1) Fixed oils of veg origin (Eg. almond/olive/soya oil)
- Use: Formulations of inj, eye-drops, liniments & oral preparations

2) Alcohols
i) For internal & external use (Ethanol)
- Commonly in low [ ] as a co-solvent with H2O in the formulation of aq solutions for oral & parenteral use

ii) For EXTERNAL use only
- Industrial methylated spirit & isopropanol

3) Polyhydric alcohol
- Commonly used as cosolvent with H2O in formulation of injections
Eg. Glycerol & Propylene glycol (Internal & External use)
Polyethylene glycols of low MW (Internal & External)

NOTE: Dipropylene glycol, diethylene glycol, ethylene glycol are VERY TOXIC!!!

4) Mineral oils & others
- More often for emulsions
- Internal & external use
- Limited use as oily & tacky nature (Veg oil prefered)

Question 16

Common additives to Solutions

Answer 16

1) Buffers
- To resist change in pH when acid/alkali is added
- Inj, eye drops & nasal drops shld preferably be buffered at physiological pH

2) Colours
- For easy identification
- Need to note that stability of colour may be affected by pH, UV & presence of oxidising/reducing agents

Types
i) Natural colours - Show variation in chemical composition
Less stable but > widely accepted
ii) Synthetic colours - Bright colours, > stable

3) Sweetening agents
i) Natural
ii) Artificial

4) Flavours & fragrances
- To make oral products more palatable & improve the appeal of products (Strong assoc between product use & its flavouring/fragrance)
- From natural/synthetic sources

5) Preservative
- Prevent microbial contamination

6) Antioxidants
- Prevent degradation of compounds by oxidation

7) Isotonicity modifiers
8) Density modifiers

Question 17

How are they evaluated for quality?

Answer 17

• Drug content
• Density (for inj into spinal fluid)
• Tonicity (IV influsion of large vol)
• Viscosity
• Clarity/particulate matter
• Colour
• Sterility