Buffers in Pharmaceutical Systems, Preparation, Stability of Buffers

Buffer in Pharmaceutical Systems

The In Vivo Biologic Buffer System

In the blood, pH is maintained at approximately 7.4. As buffers in the plasma, carbonic acid and bicarbonate, as well as acid/alkali sodium salts of phosphoric acid, are present. In the blood, plasma proteins, which act as acids, can combine with bases to act as buffers. Erythrocytes consist of two buffer systems: hemoglobin and oxyhemoglobin, and acidic, alkaline potassium salts of phosphoric acid. When carbonic acid, at body temperature and ionic strength 0.16, is ionized in the plasma, the dissociation exponent pK1 is about 6.1. Carbonic acid and bicarbonate buffer equation for blood is,

Where [H2CO3] indicates the concentration of CO2 present in the bloodstream as H2CO3. The balance of bicarbonate and carbonic acid in blood plasma with a pH of 7.4 is as follows

Or

Lacrimal fluids

It has been found that lacrimal fluid, also known as tears, can be diluted at 1:15 with neutral distilled water. There is a pH range of 7 to 8 or slightly above in tears, ranging from 7.4 to 7.4. The cornea is generally thought to be unaffected by eye drops with a pH range from 4 to 10. The discomfort will be felt below pH 6.6 and the tears will flow above pH 9.0.

Urine

Normal 24-hour urine collections of adults have a pH averaging about 6.0; they may be as low as 4.5 or as high as 7.8. Whenever urine pH falls below a normal level, hydrogen ions are excreted by the kidneys. The kidneys retain hydrogen ions in urine that have a pH above 7.4 to return the pH to a normal value.

Pharmaceutical buffers

As part of the formulation of ophthalmic solutions, buffer solutions are often used in the pharmaceutical industry. The market today offers a variety of buffer solutions. Known as PBS, phosphate-buffered saline is a common biological buffer. In phosphate-buffered saline, sodium chloride (NaCl) and sodium phosphate (Na2PO4) are combined to produce NaCl. Additionally, it may contain potassium chloride (KCl), calcium chloride (CaCl2), and magnesium sulfate (MgSO4).

In the field of pharmacy, buffers are widely used as ingredients in most pharmaceutical formulations so that the pH of the product is adjusted to the level required for the product's maximum stability. A parenteral preparation (i.e., an injection) contains: If parenteral preparations are being administered, it is very important to consider the pH since large deviations of pH can have serious consequences. It is recommended that parenteral products have a pH of 7.4, which is blood's pH. Most commonly, acetate, phosphate, citrate, and glutamate are used as buffers in parenteral products (injections).

Preparations for the eye (i.e., ophthalmic preparations):
The pH range of lacrimal fluid (eye fluid) is generally maintained by buffers in ophthalmic preparations. Although lacrimal fluid has a pH between 7 and 8, it has a good buffering capacity and can tolerate preparations with pH values between 3.5 and 10.5 without causing discomfort. A rise outside this range (i.e., 3.5 - 10.5) may result in other complications. Most ophthalmic preparations contain a buffering agent such as borate, carbonate, or phosphate.

In creams and ointments:
A buffer is used to ensure the stability of topical products (which are applied to the skin, such as ointments). Among the most common buffers found in creams and ointments are citric acid and its salts and phosphoric acid.

Preparations of buffers

Developing a new buffer should be facilitated by following the steps below.

• The weak acid should have a pKa that approximates that of the pH at which the buffer should be used.
• Calculations involving pH within the range of 4 to 10 can be approximated using the buffer equation. Use it to determine the concentration of salt and weak acid required to reach the desired pH.
• Obtain a buffer capacity that is appropriate by considering the individual buffer salt and acid concentrations. It is usually sufficient to use a concentration of 0.05 to 0.5 M and to use a buffer with a capacity of 0.01 to 0.1.
• In addition to chemical availability, sterility of the final solution, stability of a drug and buffer during aging, cost of materials, and lack of toxicity are also important considerations in selecting a pharmaceutical buffer. For instance, a borate buffer, being toxic, cannot be used as a stabilizer for parenteral or oral administration.
• Determine the buffer capacity and pH of the completed buffered solution with a pH meter. In some cases, pH papers can also be used as a gauge for determining buffer capacity and pH. pH can sometimes differ from the experimental value when the electrolyte concentration is high, especially when using the buffer equation. It is reasonable to expect this to occur when the activity coefficient is not taken into consideration, and this emphasizes the need to perform the actual determination.

Stability of buffers

There is often confusion between the terms shelf life and stability. The stability of a pH buffer refers to how long the buffer can maintain its accuracy. It takes pH buffer solutions between 24 and 60 months (2 to 5 years) before they expire. The pH buffer has been assumed to remain unopened for this period and to have remained out of adverse conditions (Example - excessive temperature).

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