**2.1.2 Biocompatibility of pharmaceuticaly used plasticizers**

The use of any material in the formulation of biomedical and medicinal devices and preparations must comply with three requirements (Zeus Industrial Products, 2005):


Biocompatibility is a general term which describes the suitability of the material in the exposure to body fluids. The material in a specific application is considered to be biocompatible if it makes it possible for the organism to function without complications, such as allergic reactions or other side effects. The complications may include chronic inflammations in contact or due to the effect of eluted components interacting with the organism, then the formation of substances which are cytotoxic, substances inducing skin irritation, restenosis, thrombosis, etc. Biocompatibility concerns medical devices and pharmaceutical products.

Various tests are used in dependence on the type of the medical device and the mode of its administration. Medical devices sold in the EU must comply with the EU Medical Device Directive 93/42/EEC, in the implemented form as 2007/47/EC, which harmonizes the legislation in the EU. At present, ISO 10993 comprises a series of 20 parts for various aspects of biocompatibility testing prior to the clinical study. ISO 14155:2011 concerns good clinical practice for the performance of safe clinical studies on human subjects. Three categories of medical device products are differentiated according to the contact with the human tissue. Limited contact is shorter than 24 hours, the prolonged one is between 24 hours and 30 days, and the permanent contact lasts for more than 30 days. Many plasticized medicated implanted systems are in the concordance with category of medical devices for permanent contact with very demanding testing.

Pharmaceutical products containing a pharmaceutical drug have as their standard for the biocompatibility check international or national pharmacopoeias, American Pharmacopoeia in the study of biocompatibility has been superseded from a major part by the standard ISO 10993. Tests following the USP are carried out on animals in three versions:


48 Recent Advances in Plasticizers

the crystallinity of the polymer, usually 5 % to 30 %, but there exist also deviations from this

When plasticizers are present in low concentrations, their effect is often the exact opposite of what is typically expected. Low concentrations of plasticizer often result in an increase in the rigidity of the polymer instead of the expected softening effect. This effect is known as antiplasticization, or effect of low plasticizer concentrations (Chamarthy Pinal, 2008).

It is of advantage when plasticizers are low volatile. The size of the molecule of plasticizers includes a wide range from a water molecule to the molecules of low-molecular oligomers and polymers. Schematically, hydrophilic and hydrophobic plasticizers are distinguished;

Because of the prevalence of fully biodegradable polymers, particularly for parenteral controlled-release systems as they do not require surgical retrieval from the body after completion of the drug release, recent research has focused on developing compatible

The use of any material in the formulation of biomedical and medicinal devices and

Biocompatibility is a general term which describes the suitability of the material in the exposure to body fluids. The material in a specific application is considered to be biocompatible if it makes it possible for the organism to function without complications, such as allergic reactions or other side effects. The complications may include chronic inflammations in contact or due to the effect of eluted components interacting with the organism, then the formation of substances which are cytotoxic, substances inducing skin irritation, restenosis, thrombosis, etc. Biocompatibility concerns medical devices and

Various tests are used in dependence on the type of the medical device and the mode of its administration. Medical devices sold in the EU must comply with the EU Medical Device Directive 93/42/EEC, in the implemented form as 2007/47/EC, which harmonizes the legislation in the EU. At present, ISO 10993 comprises a series of 20 parts for various aspects of biocompatibility testing prior to the clinical study. ISO 14155:2011 concerns good clinical practice for the performance of safe clinical studies on human subjects. Three categories of medical device products are differentiated according to the contact with the human tissue. Limited contact is shorter than 24 hours, the prolonged one is between 24 hours and 30 days, and the permanent contact lasts for more than 30 days. Many plasticized medicated implanted systems are in the concordance with category of medical devices for permanent

Pharmaceutical products containing a pharmaceutical drug have as their standard for the biocompatibility check international or national pharmacopoeias, American Pharmacopoeia

preparations must comply with three requirements (Zeus Industrial Products, 2005):

the border between them is not officially declared, the classification is subjective.

**2.1.2 Biocompatibility of pharmaceuticaly used plasticizers** 

 It must be biocompatible from the standpoint of specific use. It must comply with the complex legislative and regulatory rules.

It must comply with environmental requirements.

range.

plasticizers that also biodegrade.

pharmaceutical products.

contact with very demanding testing.

The tests called in the USP as Biological Reactivity Tests are carried out with the pharmaceutical dosage form or the medical device or the extracts obtained from them at different temperatures for different periods of action of the extraction reagent.
