Considerations and challenges with the use of NAC

Many formulations of NAC for oral administration are available as over-the- counter products. The FDA considers NAC without medical claims to be a dietary supplement, and, as such, the FDA provides minimal oversight over its production. The FTC provides some oversight regarding advertised claims and product specifications.

Although NAC has an excellent record of safety and many health benefits, it presents several challenges in manufacturing, packaging and administration for oral use. During manufacturing and storage, NAC is susceptible to degradation by oxidation. Oxidation decreases the effective concentration of the product. This is critical since the biological availability of NAC is low (34-36). Furthermore, oxidation products of NAC, such as di-NAC (NAC disulphide), may have properties that inhibit the beneficial effects of NAC treatment (3, 37) or cause rare cases of anaphylactic reactions (3, 37). Therefore, in order to obtain consistently effective serum concentrations of NAC without the presence of contaminating oxidation products, the manufacturing process must ensure that no oxidation by-products are formed, the product is in solid tablet form, excipients must provide stability and packaging must be air-tight.

Formulations of NAC must be designed for maximum and rapid absorption in the digestive tract. Aqueous formulations of NAC are unstable even when refrigerated (38). PharmaNAC® is most stable as a solid tablet protected from moisture and air (38).

Finally, some individuals find it difficult to use NAC because of the odor, or the odd taste due to its sulfur content. Some individuals have an increased propensity for stomach upset from NAC. A formulation of NAC that is universally palatable is important for patient compliance with health care instructions.

Advantages of an effervescent formulation of NAC

BioAdvantex Pharma esponds to the issues of purity, stability, pharmacokinetics and bioavailability, palatability and gastrointestinal compatibility by its formulation of NAC as effervescent tablets that are individually wrapped in airtight packaging.

Purity

Thiolex only provides licenses to manufacturers that make its products according to European Good Manufacturing Practice (GMP) and which are controlled according to pharmaceutical guidelines.

Each effervescent tablet is individually wrapped in a special four-layer (paper/plastic/foil/plastic) air-tight package. This packaging prevents moisture and air from contacting the tablet. Individual packing of each tablet means that a tablet is not exposed to air until just prior to use. Individually wrapped tablets also make each dose portable; travel is easy and refrigeration is not needed.

Stability of effervescent tablets upon dissolving in water

Tablets dissolve in water (or juice) just prior to use. Buffers in the excipients must maintain a pH that inhibits oxidation for the short time period required for the product to dissolve before it is ingested. The aqueous formulation ensures rapid and complete absorption into the blood by allowing the active ingredient to immediately spread over a large surface area of the digestive tract. The effervescent tablet ensures maximum bioavailability of the active ingredient.

Packaging of must ensures NAC stability and purity

Thiolex brand n-acetylcysteine is certified compliant to the standards of both the European Pharma (Ph. Eur.) and United States Pharmacopoeia (USP). Following these standards of quality control means that the product contains minimal degradation products of NAC from oxidation or other causes (3).

Pharmacokinetics and Bioavailability

Effervescent formulations provide several advantages with regard to the pharmacokinetics and bioavailability of therapeutic agents (39). Specifically, effervescent agents increase the onset of action of the active ingredient by increasing solubility (40), absorption (39, 41, 42) and transport out of the digestive tract (39, 43, 44). The carbon dioxide produced upon dissolving the product in water (or juice) causes an increase in paracellular transport of the active ingredient, NAC, from the digestive tract to the blood (39, 43). Taken together, increased solubility, absorption and transport leads to an increase in the onset of the therapeutic benefits of NAC action.

Overall benefits

Thiolex-licensed products are manufactured according to standards of the European and US Pharmacopoeias that insure a product of maximum purity.

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