What Revisions Has U.S. Pharmacopoeia Made to Pharmaceutical Excipients?

Pharmaceutical excipients are natural or synthetic substances formulated together with the active ingredients of the drug, whose purpose is to increase the formulations containing effective active ingredients or endow the active ingredients in the final dosage form with therapeutic effects, such as promoting drug absorption or solubility. Pharmaceutical excipients can also be used in the manufacturing process, for example, by promoting the flowability or non-stick properties of the powder to assist in the handling of related active substances. In addition, they can also assist in vitro stability, such as preventing denaturation during the expected shelf life. The choice of suitable excipients also depends on the route of administration and dosage form, as well as the active ingredient and other factors.

Although pharmaceutical excipients are not directly involved in the metabolic process of drugs in the body, they do have an important impact on indicators of stability, pH, permeability, bioavailability, safety and transparency of tablets, capsules, injections, and oral liquids. The new edition of the United States Pharmacopoeia (USP29 NF24), which has been implemented since 2008, has revised the standards of certain pharmaceutical excipients, further improved the quality standards of pharmaceutical excipients and added several new excipient items.

The new edition of the United States Pharmacopeia contains a total of 40 categories and more than 800 varieties of medicinal excipients, and redefines the definition of excipients. The new version stipulates that the role of pharmaceutical excipients in pharmaceuticals is to: improve the solubility and bioavailability of the drug substance; improve the stability of the drug substance in the preparation; maintain the rational polycrystalline form of the drug substance in the preparation; maintain the pH value or osmotic pressure of liquid pharmaceutical preparations; prevent raw materials, especially in protein drugs or polysaccharide drugs, from the aggregation reaction or depolymerization reaction; improve the immune response of drugs and other similar reactions. Also, pharmaceutical excipients can be used in tablets as binders, disintegrants or antioxidants in liquid preparations, emulsifiers and propellants in aerosols.

With the continuous expanding of new bioengineered drugs, the US Pharmacopoeia will continue to add new medicinal excipient products in the future. However, in principle, the newly added medicinal excipients must first apply for NDA (New Drug Approval) test and establish relevant quality standards, and secondly, they must be generally recognized as safe substances, namely GRAS-grade raw materials; otherwise, they cannot be approved for use as a pharmaceutical excipient.

It is worth noting that the new edition of the United States Pharmacopeia has revised the standards of some excipient products, such as stipulating that the particle diameter of lactose is 4.6 microns. In addition, new varieties and standards have also been included, such as the addition of infrared or ultraviolet spectroscopy standards for several pharmaceutical/cosmetic excipients, and the official inclusion of multifunctional excipients suitable for modern high-speed tablet presses for tablet processing- PPG1500 starch and so on.

Excipients for orally disintegrating tablets 

In the past, the pharmacopoeias of various countries did not have special regulations on the excipients used for orally disintegrating tablets, but the new version of the US Pharmacopoeia also included some excipients for orally disintegrating tablets.

The key excipients used in orally disintegrating tablets are particle coating agents, which are all hydrophilic cellulose polymers such as EC (ethyl cellulose) and HC (hydroxy cellulose). The new version of the United States Pharmacopoeia stipulates that the excipients used for orally disintegrating tablets must be granular ethyl cellulose or hydroxy cellulose with a diameter of 4-6 microns.

Polyvinyl pyrrolidone

Polyvinyl pyrrolidone (PVP) such as Ludiflash is a commonly used pharmaceutical excipient product. There is a large demand for PVP in the international market. The new version of the United States Pharmacopoeia has set up a new infrared spectroscopy standard for the quality standard of PVP to control its impurity content and prevent low-quality PVP from being used in pharmaceutical preparations.

Gelatin

Gelatin is also pharmaceutical raw material that is widely used in pharmaceutical preparations. The new edition of the United States Pharmacopoeia has revised the quality standards of gelatin, and revised a number of standards such as product appearance, color, (gelatin liquid) viscosity, and molecular weight.

Chitins

Chitin (chitosan) has actually been used in pharmaceutical products for a long time. The United States Pharmacopoeia has newly added the quality standards for the raw materials of two chitin derivatives, TMC (N-trimethyl chitosan chloride) and chitosan ester.

Chitin is the second largest natural polysaccharide polymer in nature only after cellulose. It is mainly extracted from by-products of aquatic processing industry such as shrimp and crab shells. Chitin is insoluble in water and must be chemically modified to become other derivative products before it can be used in pharmaceutical preparations. Water-soluble chitin compounds are mostly used for processing into sustained-release preparations or as stabilizers for liquid pharmaceuticals. Recently, researchers have discovered that water-soluble chitin compounds have good mucosal adhesion and are very suitable as special excipients for gastric preparations for the treatment of gastric and duodenal ulcers. The newly included TMC and chitosan esters are very suitable for these new applications.