pH modifier excipients

pH modifier excipients are used in the pharmaceutical industry due to their antioxidant properties. pH modifiers can help maintain the stability of pharmaceutical and can also be used as preservatives. For pH-modification, the addition of a base or an acid is often preferred over the use of buffers. Acidic or basic ingredients (pH modifiers) can be intentionally added to a formulation for the sole purpose of modifying the ‘pH.’ but parameters like salt selection and pH value are critical in the pre-formulation stages, the use of excipients to make pH adjustments is also a significant factor in designing the drug’s formulation and delivery and should not be overlooked.

Adjustment of the pH value is the simplest and most commonly used method of increasing the water solubility of ionisable compounds. The solubility of therapeutic agents is pH dependent. The solubility of acids and bases increases as the degree of ionization increases. The solubility of acidic compounds increases as the pH of the solution is increased (above the pKa) and solubility of basic compounds increase as the pH is lowered below the pKa. The system works on the principle that natural changes in pH value within the gastrointestinal tract influence the bioavailability of pharmaceuticals.

The pH of the boundary layer (or stagnant diffusion layer) on the surface of solid drug particles is of special importance for the dissolution of weak acidic and basic drugs. It is possible to improve the dissolution rate of weak acidic and basic drugs by including pH- modifier excipients in a formulation that is capable of changing the pH of the stagnant diffusion layer or micro-environment. pH- modifier excipients are mixed with the other ingredients of a solid oral dosage form prior to being compressed into tablets or filled into capsule shells. When disintegration of the dosage form takes place, these excipients dissolve in the fluids of the gastrointestinal tract. These excipients then cause a pH adjustment of the stagnant diffusion layer due to provision of H+ or OH− ions (depending on whether decreasing or increasing of pH is desired) that favors the dissolution of the active ingredient by forcing its molecules to exist more in the ionized state. 

Drug absorption is largely dependent on diffusion, and this varies with the pH value of different regions within the gastrointestinal tract, and the acid dissociation constant (pKa) and permeability of the drug. The absorption process is moderated by the surface area of the region of release and its pH value, which affects drug ionisation. If the pH value of a drug product with low water solubility is changed, parts of the molecule that may be protonated (base) or deprotonated (acid) may acquire the potential to be dissolved in water.

Example: pH- modifier excipients that can be used to improve the dissolution rate of weak basic drugs include organic acids (e.g., citric acid, tartaric acid and carbonic acid). After disintegration of a solid dosage form, the organic acid dissolves in the surrounding gastric juices and lowers the pH of the stagnant diffusion layer surrounding each drug particle, creating a desirable environment for the dissolution and consequently the absorption of alkaline drugs. Acidic drugs, on the other hand, would exhibit an improved solubility as well as dissolution rate in an alkaline micro-environment since they will exist more in the ionized state. 

Below examples will enhance your understanding:

Effect of NaHCO3 and CaCO3 on Paracetamol

Inclusion of NaHCO3 in tablets results in a faster absorption of paracetamol as indicated by a lower Tmax value and higher Cmax value. Furthermore, the inclusion of NaHCO3 also reduces the variability in absorption. The increase in absorption of paracetamol upon the inclusion of NaHCO3 in the tablet formulations is partly attributed to an increase in in vivo dissolution rate. It is, however, interesting to note that this effect is not seen with the inclusion of CaCO3, and the reason for this occurrence is not clear yet. 

Conclusion: 

Finally, selecting a pH- modifier excipients for a formulation requires a systematic approach with careful consideration of the performance of final products.

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About the Author:

Dr. Ajay Kumar Singh, M.Sc. (Gold Medalist), Ph.D. is the author and founder of “Pharma Solutions by Dr. Ajay”.

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