Pharmaceuticals chronic administration

In addition to national approvals and lists, a pharmaceutical licensing authority can impose additional restrictions at the time of application review. Within the EU this generally takes the form of restricting colors, such as tartrazine and other azo colors, in medicinal products for chronic administration, and especially in medicines for allergic conditions. 

Boric acid and borax (ADI = 0.1 mg/kg body weight) resorb rapidly in the body and are slowly excreted. In comparison with other acids, which act as preservatives, these compounds are more toxic, but no side effects are known from foods. Concentrations of boric acid (borates) in pharmaceutical preparations are much higher and may cause several side effects. Chronic administration causes bleeding, dermatitis and anaemia. 

Food and Drug Administration (FDA) (2001). Guidance for Industry Statistical Aspects of the Design, Analysis and Interpretation of Chronic Rodent Carcinogenicity Studies of Pharmaceuticals. USDHEW, Washington, D.C. 

In Japan, Uchiyama has recently published requirements for the safety evaluation of new excipients. These requirements include studies on acute, subacute, and chronic toxicity, mutagenicity, effects on reproduction, dependency, antigenicity, carcinogenicity, and local irritation (human patch test). The first five of these tests are mandatory. With the exception of the local irritation test, for which a domestic trial is required, non-Japanese data are acceptable for these studies. Even if a material has been used in a pharmaceutical product outside Japan, the material is treated as a new excipient if there has been no prior use in Japan, although relevant overseas data for the material are acceptable for regulatory submission. A material is treated as a new excipient when the route of administration differs or the dose level exceeds that of prior use even after approval for the Japanese market.f ... 

Particle design applied to pharmaceutical processing has the potential to improve the efficacy of current medications as well as to open the way to the use of alternative delivery routes. An example is the administration of drugs, such as insulin, that are subject to extensive gastrointestinal breakdown and thus cannot be administered orally. The alternative is parenteral administration, which has major side effects, especially in long-term or chronic conditions. 

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