Pharmaceutical requirements

Many crystalline products, including fine chemicals, foodstuffs and pharmaceuticals, require a final particle size that is significantly smaller than that produced during the crystallization or precipitation step. One way of achieving the required particle size is to employ a subsequent size-reduction step using some form of comminution device, frequently a mill. 

Bj 23.3 g of 2,6-dihydroxymethylpyrldine-bis(N-methylcarbamate), prepared as described above, are dissolved in a boiling mixture of 46.6 ml of methanol and 46.6 ml of water. When the dissolution is complete, the solution is allowed to cool under slow stirring, without applying any external cooling means. The crystals start to separate at 48°C to 50°C. When the temperature of the mixture falls spontaneously below 35°C, it is cooled externally to 0°C to 5°C, and allowed to stand at this temperature for about 8 hours. Theseparated substance isfiltered off and dried at 50°C to 100°C. 22.65 g of 2,6-dihydroxymethylpyridine-bis(N-methylcarba-mate) are obtained. The quality of the product meets pharmaceutical requirements. 

GC-MS is applied in some methods for the analysis of pharmaceuticals in sludge [45, 109]. However, this technique can only be successfully applied for a limited number of nonpolar and volatile pharmaceutical compounds, while analysis of polar pharmaceuticals requires a time-consuming and often irreproducible deriva-tization. Consequently, LC-MS is the preferred technique in many laboratories. Some other detection techniques are also employed, such as diode array (DAD) and electrochemical (ED) and fluorescence detection (ELD). In the case of fluoroquinolones, ELD is still the favored technique. 

In addition to rodent studies, regulatory guidelines for pharmaceuticals require that repeated dose safety studies of up to nine months (in the United States, six months elsewhere) in duration be conducted in a nonrodent species. The most commonly used nonrodent species is the dog, followed by the monkey and pig. Another nonrodent model used to a limited extent in systemic safety evaluation is the ferret. The major objectives of this chapter are (1) to discuss differences in rodent and nonrodent experimental design, (2) to examine the feasibility of using the dog, monkey, pig, and ferret in safety assessment testing, and (3) to identify the advantages and limitations associated with each species. 

To circumvent some of the above-mentioned drawbacks of sulfur-based mercury chemodosimeters, a system based on the alkyne oxymercuration of 58 has been developed (Fig. 22) [146]. 58 shows high selectivity, a limit of detection of ca. 8 ppm, resistance against strong oxidants, and a positive reaction even in the presence of cysteine, which is known to form stable mercury complexes and is used for the extraction of mercury from tissue samples. Another metal that is well-known for its catalytic ability is palladium, catalyzing different reactions depending on its oxidation state. Since this metal is toxic, assessment of the maximum allowable concentration of Pd in consumer products such as pharmaceuticals requires highly sensitive and selective detection schemes. For this purpose, indicator 60 was conceived to undergo allylic oxidative insertion to the fluorescein... 

Most analyses of pharmaceuticals require an extraction step or extractions steps and optimisation of these prcx esses has an important bearing on the precision and accuracy of the analysis... 

The statin family of pharmaceuticals require a chiral side chain, representing a target that has attracted a great deal of activity focused on preparing various potential intermediates. A number of reports have been published on the reduction of chloroacetoacetate esters for conversion into this target molecule. A method suitable for large-scale production has been published that operates at 36.6gL and 95.2 % yield with 99% ee. This reaction is shown in Figure 1.43. 

Sterilization effect. Pharmaceutical requirements dictate that the generators be either aseptically produced or sterilized by... 

The pharmaceutical requirement to maintain eluate sterility and apyrogenicity,... 

There is a remarkable degree of harmonisation between the USP approach and the ICH 3 Note for Guidance on validation of analytical methods for the pharmaceutical industry and the NMLK No. 4 guidelines for the food industry. 5 The requirements for the latter two are given in Table 12. For more detailed discussion of the pharmaceutical requirements see ref. 28. 

The production of powders of pharmaceutical, required to improve or modify their therapeutic action or to enhance their solubility. 

The jury is still out on the clinical efficacy of texaphyrin-based therapeutics the commercialization of novel pharmaceutics requires careful negotiation through the minefield of clinical trials and the subsequent analysis of the data. Nevertheless this example should serve as an inspiration to chemists everywhere. 

Nowadays, there are additional requirements on bioprocess monitoring systems. These are partly due to governmental regulations on the production of pharmaceuticals, requiring vahdated processes delivering, for example, a constant yield of cells, product and product quality. The latter includes not only the quality of the product itself, such as the biological activity of a therapeutic protein, but also its purity, i.e., the presence or absence of interfering compounds [22,23]. 

Imbalance with respect to the production of basic drugs and pharmaceuticals required for formulations. The current consumption of drugs is valued at 94 million, and the indigenous production is worth about 62.5 million. 

Reply 99.9% of pharmaceutical require a degree. We have had success placing non-degreed candidates, but those candidates had sales experience in medical supply sales. I want to stress that the most important sales experience is outside sales. 

The importance of a visual technique, such as HSM, lies in its ability to provide information for the confirmation of transitions that are observed using other techniques. As stated earlier, the characterization of the physical properties of many materials, including pharmaceuticals, requires a multidisciplinary approach in which a number of techniques are utilized to confirm suspect transitions. To illustrate the need for this characterization philosophy, several examples, along with numerous photomicrographs showing the benefit that a visual technique such as HSM can provide, are presented. 

The determination of trace metal impurities in pharmaceuticals requires a more sensitive methodology. Flame atomic absorption and emission spectroscopy have been the major tools used for this purpose. Metal contaminants such as Pb, Sb, Bi, Ag, Ba, Ni, and Sr have been identified and quantitated by these methods (59,66-68). Specific analysis is necessary for the detection of the presence of palladium in semisynthetic penicillins, where it is used as a catalyst (57), and for silicon in streptomycin (69). Furnace atomic absorption may find a significant role in the determination of known impurities, due to higher sensitivity (Table 2). Atomic absorption is used to detect quantities of known toxic substances in the blood, such as lead (70-72). If the exact impurities are not known, qualitative as well as quantitative analysis is required, and a general multielemental method such as ICP spectrometry with a rapid-scanning monochromator may be utilized. Inductively coupled plasma atomic emission spectroscopy may also be used in the analysis of biological fluids in order to detect contamination by environmental metals such as mercury (73), and to test serum and tissues for the presence of aluminum, lead, cadmium, nickel, and other trace metals (74-77). 

The Pharmaceutical Development group can play a leading role in determining the pharmaceutical requirements for a new product from key customers. Customers may want more specific packs or delivery systems, and different markets still have their own preferences for different dosage forms. 

With the rapid increase in the incidence of diabetes among the population, it is no longer possible to satisfy the pharmaceutical requirement (estimated to be 15-20 tonnes per year in 2005) from animal sources. Furthermore, the animal-extracted insulins are slightly different from human insulin, which might cause formation of insulin-binding antibodies and allergic reactions. Porcine insulin, which differs from human insulin only by a single amino acid in position B30, can be converted to human insulin in a transpeptidation reaction, in which an alanine is replaced with a threonine [1]. 

The protective value of the tin coating increases with coating weight. The more corrosive chemicals and certain pharmaceuticals require use of coatings at the top end of the range. 

Cold kits may also be prepared in a radiopharmacy similar to other medicinal products prepared in a pharmacy. The radiopharmacist then functions as the qualified person responsible for preparation of an official formula (formulation, pharmaceutical requirements, stability, etc.)... 

Given a wealth of natural chemical scaffolds for improved drug design, our ability to generate novel pharmaceuticals requires increased understanding of the biosynthetic processes that may lead to their discovery and production. Polyketide and nonribosomal peptide assembly offers enormous potential for development of combinatorial biosynthetic methods. The structural complexity of these natural products often prohibits practical chemical synthesis, which underscores the need for alternative means of accessing them in usable quantities. Research in this area requires in-depth knowledge of chemical,... 

Pharmaceutical Requirements in Dried Particles and Its Associated Processes.995... 

PHARMACEUTICAL REQUIREMENTS IN DRIED PARTICLES AND ITS ASSOCIATED PROCESSES... 

Then there are a number of more technical requirements for the process to be as green as possible. Many procedures in organic chemistry, as in the fabrication of pharmaceuticals, require intermediate steps in which molecules are modified temporarily on their way to becoming the final product. Each step needs special conditions, its own reagents, and perhaps a variety of noxious solvents. The procedure shifts towards the green end of the production spectrum by minimizing these intermediates and looking for more direct routes from feedstock to product. 

Freeze diying is a well-established drying technology to meet certain pharmaceutical requirements (lyophilization). It is also used for some food products like berries, which need to be quickly reconstituted (moistened) during meal preparation. A freeze drying process is composed of two process steps. First, the wet product... 

All new chemical entities (NCEs) proposed as pharmaceuticals require extensive testing before they can... 

These provide a safer alterative to glass containers although limited availability, the need to use specialist filling and sealing equipment and the requirement to conform to regulatory pharmaceutical requirements has restricted their use. 

Increase of strength is possible by chemical or thermal toughening, but it is a rather expensive step and in contradiction to the pharmaceutical requirement of delivering stress-free glass [6], Nevertheless in special applications it might be useful. 

The main economic objective of process control is to achieve maximum productivity or efficiency while maintaining a satisfactory level of product quality. Manufacturing facilities in the production of chemicals, paper, metals, power, food, and pharmaceuticals require accurate and precise control systems. Although the methods of production vary from industry to industry, the principles of automatic control are generic in nature and can be universally applied, regardless of the size of the plant. 

Xenon (Xe) represents an innovation in the field of anaesthesia. Its narcotic effect was discovered only in 1951. Clinical studies proved the principle applicability even as mono-anaesthetic. The marketing of xenon as finished pharmaceutical requires authorization according to the current drug law regulations. The high price for xenon can be reduced by its recycling from exhaled gas. In order to enable the substitution of all anaesthetics by xenon, considerable increases in capacity of air separation plants would be required. 

Note Biological pharmaceuticals require extensive biochemical and bioactivity comparability studies for materials used for toxicology, clinical and proposed market supplies. 

---