Quality of the Active Substance

Different oral liquid dosage forms offer the possibility to adjust the dosage form optimally to the requirements. The options are solutions, suspensions, emulsions or solubilisates. The flow scheme in Fig. 5.1 shows a route to the oral liquid form that is to be preferred due to the qualities of the active substance, particularly solubility, stability and taste. The required concentration influences the choice as well. 

Determination of the contamination profile of the active substance (active pharmaceutical ingredient) and the final product (dmg product) is a broad and time-consuming process, the goal of which is to guarantee the quality of the medicinal product. Quality of the product is one of the most important factors in terms of the safety of pharmacotherapy. 

Application for a Quality Certificate to the Institute for Standardization and Control of Pharmaceuticals (See a translation of the application form in Appendix 3). With this application, samples of the finished product and of the active substance(s) and their respective certificates of analyses must be submitted. The final approval of the application for registration is contingent upon the availability of the Quality Certificate. Separate applications have to be submitted for each dosage strength. 

The quality of specified active substances and excipients has to meet, in Europe, the European Pharmacopoeia criteria and thus are named according to the English monograph titles. If not included, another reference pharmacopoeia is given. 

In compression molding, the mixture in the mortar is transferred to special pressing equipment, holding the proper compression mold (see Fig. 11.2). The method requires a replacement factor (see Sect. 11.5.1) specifically valid for this compression method. In both cold methods the quality of mixing active substance and grated base is very critical for sufficient content imiformity of the suppositories. Although no investigations are available, it is obvious that this process is most critical with low-dosed active substances and definitely has to be validated. 

A homogeneous distributirai of the active substance within one suppository is not important for its therapeutic effect If the active substance has settled to the tip, it may indicate a too high pouring temperature. If sedimentation is so extensive that the tip has become brittle and breaks, the quality is insufficient... 

The functionality of the medicinal product can be described both in technical and biopharmaceutical terms. The technical terms encompass aspects such as stability, uniformity of dosage and microbiological quality of the product. The biopharmaceutical functionality of a medicinal product relates to aspects such as the drug release profile, suitability of the medicinal product for administration via the intended route and ability of the active substance to reach the site of action. In this chapter the basics of biopharmaceutics are described and explained in relation to the different aspects of formulation, routes of administration and therapeutic objectives. 

It is also stated that the amount of a drug substance of a medicine prepared in the pharmacy does not deviate more than 10 % of the amount of that substance that is mentioned on the label of the container. For the average content of the active substance the quality requirements from a foreign Pharmacopoeia are not applicable. It is important to note that all quality requirements are valid in principal until the expiry date of the product. 

The quality of a drug substance is controlled by its specification. An internationally harmonized guideline on specifications and tests for chemical substances as active ingredients and in drug products makes reference to chiral compounds. This has recently been finalized and is discussed in Section 13.5.2. 

Guidance on specifications is divided into universal tests/criteria which are considered generally applicable to all new substances/products and specific tests/criteria which may need to be addressed on a case-by-case basis when they have an impact on the quality for batch control. Tests are expected to follow the ICH guideline on analytical validation (Section 13.5.4). Identification of the drug substance is included in the universal category, and such a test must be able discriminate between compounds of closely related structure which are likely to be present. It is acknowledged here that optically active substances may need specific identification testing or performance of a chiral assay in addition to this requirement. 

As mentioned, AOS is a complex mixture of anionic active substances the nature of which is dependent on the quality of the olefin feed and the manufacturing processes employed. Formulations utilizing AOS are developed according to the level and type of these active species. Analytical procedures are therefore required to define their level and nature. 

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