Active pharmaceutical ingredient defined

This chapter provides an introduction to the pharmaceutical sector, and the business of developing new active pharmaceutical ingredients (API). Crystallization is the preferred method of isolating commercial API products because it offers a highly efficient means of purification. The crystallization process is also where the physical properties of the drug substance are defined. These properties can have a significant impact on the formulated product and process, and eventually on the drug release profile in the patient. 

Due to the brick-and-mortar structure of the stratum corneum, the skin is a difficult layer to permeate across for most active pharmaceutical ingredients. Because of this diffusional barrier, new strategies have been developed to allow compounds to better penetrate the stratum corneum [28], These strategies can be defined as either chemical or physical approaches to disrupting the barrier function of the skin. 

Drug substance-. The drug substance (DS), also known as a new chemical entity (NCE) or the active pharmaceutical ingredient (API), in early phases of drug development consists of the following components (a) active moiety, (b) counter-ion, and (c) water or solvent molecules that are known components of the DS crystal structure. If the single crystal structure of the DS is unavailable, the DS can be defined as a hydrate or solvate based on the results of other analytical tests and the scientific judgment of the scientist. 

The rate and extent to which the active moiety is absorbed from a pharmaceutical dosage form and becomes available at the site(s) of action. Reliable measurements of drug concentrations at the site(s) of action are usually not possible. The substance in the general circulation, however, is considered to be in equilibrium with the substance at the site(s) of action. Bioavailability can be therefore defined as the rate and extent to which the active pharmaceutical ingredient or active moiety is absorbed from a pharmaceutical dosage form and becomes available in the general circulation. Based on pharmacokinetic and clinical considerations it is generally accepted that in the same subject an essentially similar plasma concentration time course will result in an essentially similar concentration time course at the site(s) of action. 

Analytical method goals are often defined as method acceptance criteria for peak resolution, precision, specificity, and sensitivity. For instance, pharmaceutical methods for potency assays of an active pharmaceutical ingredient (API) typically require the following resolution >1.5 from the closest eluting components precision of retention time and peak area, <1-2% RSD and linearity in the range of 50-150% of the label claim. Other desirable characteristics include ... 

Steps that are critical for the quality of the active pharmaceutical ingredient should be defined and the procedures applied should be validated. 

Active pharmaceutical ingredient An ingredient to which a defined pharmacological activity is attributed. 

In summary, biogenerics are best defined as copies of therapeutic proteins, launched after patent expiry of the active pharmaceutical ingredient, and sold with a moderate price reduction. They have to be approved via the route of the centralized procedure in Europe and currently require a complete stand-alone dossier including clinical studies proving efficacy and safety. 

Excipients contained in the original dosage form also have to be taken into account and can decrease the product s appearance (insolubles) or even reduce the drug stability. The end-product is therefore a complex and not well-defined admixture of numerous components. Ideally, it should be prepared with the pure active pharmaceutical ingredient when possible. 

Many active pharmaceutical ingredients fall in the former category where the toxicologically defined limit becomes meaninglessly high seen... 

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