To encounter stability problems all liquid formulation should be formulated to an optimum pH. Rheology, viscosity and other property are dependent on the pH of the system. Most liquid systems are stable at pH range of 4-10.

This is the most important in case where API consists of ionizable acidic or basic groups. This is not a problem when API consists of neutral molecule having no surface charge.e.g. Steroids, phenacetin, but control of pH is strictly required as quality control tool.

Buffers are employed within pharmaceutical solutions to control the pH of the formulated product. When buffers dissolved in a solvent, it will resist any change in pH when an acid or base is added. Buffers used should be compatible with other additives and simultaneously they should have less toxicity. Generally pH of suspension should be kept between 7-9.5, preferably between 7.4-8.4. Most commonly used buffers are salts of week acids such as carbonates, citrates, gluconates, phosphate and tartrates.

Amongst these, citric acid and its pharmaceutically acceptable salts, phosphoric acid and its pharmaceutically acceptable salts are commonly used in suspension formulation. However, Na phosphate is most widely used buffer in pharmaceutical suspension system.

Citric acid is most preferable used to stabilize pH of the suspension between 3.5 to 5.0.

L-methionine is most widely used as buffering agent in parenteral suspension. Usual concentration of phosphoric acid salts required for buffering action is between 0.8 to 2.0 % w/w or w/v. But due to newly found super-additive effect of L-methionine, the concentration of phosphoric acid salts is reduced to 0.4 % w/w or w/v or less.

Examples of buffer salts used in pharmaceutical solutions include:
  • acetates (acetic acid and sodium acetate): circa 1–2%
  • citrates (citric acid and sodium citrate): circa 1–5%
  • phosphates (sodium phosphate and disodium phosphate): circa 0.8–2%.

Typically pH control is performed:
  • to maintain the solubility of the therapeutic agent in the formulated product. The solubility of the vast number of currently available drugs is pH-dependent and, therefore, the solubility of the therapeutic agent in the formulation may be compromised by small changes in pH
  • to enhance the stability of products in which the chemical stability of the active agent is pH-dependent.

Buffers have four main applications in suspension systems that are mentioned below:
  • Prevent decomposition of API by change in pH.
  • Control of tonicity
  • Physiological stability is maintained
  • Maintain physical stability
For aqueous suspensions containing biologically active compound, the pH can be controlled by adding a pH controlling effective concentration of L-methionine. L-methionine has synergistic effects with other conventional buffering agents when they are used in low concentration.

Preferred amount of buffers should be between 0 to 1 grams per 100 mL of the suspension.

It must be remembered that the buffer system used in solution formulations should not adversely affect the solubility of the therapeutic agent, e.g. the solubility of drugs may be affected in the presence of phosphate salts.