Active pharmaceutical ingredients APIs

These and other FDA policy decisions launched the pharmaceutical industry and academia into a new era of developing stereoselective processes for the manufacture of enantiopure active pharmaceutical ingredients (APIs). 

Although in many cases an enantiopure drug can be safer than the racemate, the advantages are clear. The final formulation of the drug product could be reduced inhalf, potential side effects could be minimized, and the resulting pharmokinetic and pharmacodynamic studies could clearly determine the efficacy of the active pharmaceutical ingredient (API) [21]. 

Figure 11.5 Headings of ICH CMP guideline for Active Pharmaceutical Ingredients (API) manufacture.

However, compared with the traditional analytical methods, the adoption of chromatographic methods represented a signihcant improvement in pharmaceutical analysis. This was because chromatographic methods had the advantages of method specihcity, the ability to separate and detect low-level impurities. Specihcity is especially important for methods intended for early-phase drug development when the chemical and physical properties of the active pharmaceutical ingredient (API) are not fully understood and the synthetic processes are not fully developed. Therefore the assurance of safety in clinical trials of an API relies heavily on the ability of analytical methods to detect and quantitate unknown impurities that may pose safety concerns. This task was not easily performed or simply could not be carried out by classic wet chemistry methods. Therefore, slowly, HPLC and GC established their places as the mainstream analytical methods in pharmaceutical analysis. 

The use of palladium as a catalyst is common in the development and synthesis of active pharmaceutical ingredients (APIs). Palladium is an expensive metal and has no known biological function. Therefore, there is a need to recover spent palladium, which is driven both by cost and by government regulations requiring residual palladium in APIs to be <5 ppm (1). Thus, much research has been conducted with the aim of heterogenizing active palladium that can then be removed via simple filtration and hopefully reused without significant loss of activity. 

Synthesis and scale-up production of active pharmaceutical ingredient (API)... 

To get a better idea of the complexity of a real application scenario in these industries it makes sense to, once, exemplarily depict the planning processes in a typical production of active pharmaceutical ingredients (API production). Most pharmaceutical companies are looking at planning scenarios in which several hundred individual resources or facilities have to be accounted for, with demands and orders for some thousand final products. The planning horizon is often set to 2-5 years. Next to single equipment, there are facility pools, with one pool consisting of several individual units. 

The pharmaceutical industry produces between 25 and 100 kg or more of waste for every kilogram of active pharmaceutical ingredient (API) manufactured.1 According to a leading practitioner of the industry, the potential waste coproduced with APIs is in the range of 500 million to 2 billion kg per year. Even at a nominal disposal cost of 1 per kg, the potential savings just in waste avoidance is significant faced to the pharmaceutical industry annual sales (almost 500 billion in 2003). 2... 

Sol-gel microencapsulation in silica particles shares the versatility of the sol-gel molecular encapsulation process, with further unique advantages. Sol-gel controlled release formulations are often more stable, potent and tolerable than currently available formulations. The benefits of microencapsulation can be customized to deliver the maximum set of benefits for each active ingredient. Overall, these new and stable combinations of active pharmaceutical ingredients (APIs) result in improved efficacy and usability. 

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. 

It is a general requirement for an optimal therapeutic effect that the active pharmaceutical ingredient (API) is delivered to the site of action in order to provide effective but not toxic concentration levels. Therefore, studies to measure BA are of great importance in order to support new drug product applications. Thus, data on the BA of orally administered drug products is a general requirement to the development... 

Borman, P. J., Chatfield, M. J., Crowley, E. L., Eckers, C., Elder, D. P., Francey, S. W., Laures, A. M-F., Wolff, J-C. Development, validation and transfer into a factory environment of a liquid chromatography tandem mass spectrometry assay for the highly neurotoxic impurity FMTP (4-(4-flurophenyl)-l-methyl-l,2,3,6-tetrahydropyridine) in paroxetine active pharmaceutical ingredient (API). J. Pharm. Biomed. Anal., 48, 2008, 1082-1089. 

The Guidance applies to the manufacture of active pharmaceutical ingredients (APIs) for use in human drug products. It is detailed in Table 9.1. 

Safety Production of the requisite drug molecule, called the active pharmaceutical ingredient (API) or bulk pharmaceutical chemical (BPC), may involve materials, solvents, or intermediates that are volatile, toxic, or even explosive. The development program has to determine the appropriate manufacturing processes to ensure that safety is not compromised and the API can be produced and purified to remove impurities and toxic residues. 

An introduction to Taxol (Bristol-Myers Squibb) is presented in Exhibit 3.4. The active pharmaceutical ingredient (API) is paditaxel. The chemical name is 5j8,20-epoxy-l,2a,4,7)3,10i3,13a-hexahydroxytax-ll-en-9-one 4,10-diacetate 2-benzoate 13 ester with 2R, 3S)-N-benzoyl-3-phenylisoserine. 

The resulting drug substances, called active pharmaceutical ingredients (APIs), are recovered and purified from solvents. More recent methods aim to isolate chiral compounds to improve drug-target interactions. 

Pharmaceuticals, for the purpose of this book, means chemical compounds that are used in pharmaceutical production. This can comprise the active ingredient, which is also called active pharmaceutical ingredient (API) or drug substance or drug product and the inert pharmaceutical ingredients (excipients) that are used to formulate a drug product in the form of tablets, capsules, ointments, creams, lotions, parenterals, inhalers, and a variety of drug delivery systems. 

Examined factors were organic solvent concentration, buffer or electrolyte concentration, - - buffer or electrolyte pH,7 7 - T83,85,86 voltage,chiral selector concentration " and supplier, active pharmaceutical ingredient (API) concentration, internal standard concentration, injection time - and pressure, ... 

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