Drug Development

In the biological arena, new and highly useful fluorescent markers are used to stain or 'label' specific structures of interest. They have transformed the range and applicability for optical observation. These labels are excited and correspondingly emit at specific wavelengths; thus, different facets of a specimen can be 'selected' by controlling the wavelength of the delivered and captured light. For example, labels such as 4',6-diamidino-2-phenylindole (DAPI) are used to highlight the nucleus of a cell and MitoTracker Orange is used for mitochondria. Figure 1 shows an example of a multiple stained section, viewed in fluorescence. There has been an explosion in fluorescent labels for examining biological structures, in fixed and live cell preparations.

High-performance liquid chromatography (HPLC) is a powerful tool for the enantioselective separation of chiral drugs. However, the selection of an appropriate chiral stationary phase (CSP) and suitable operating conditions is a bottleneck in method development and a time- and resource-consuming task. Multimodal screening of a small number of CSPs with broad enantiorecognition abilities has been recognized as the best strategy to achieve rapid and reliable separations of chiral compounds. This paper describes the generic screening strategy developed at Johnson & Johnson Pharmaceutical Research and Development to successfully develop enantioselective HPLC methods for chiral molecules of pharmaceutical interest.

In 2007, the global pharmaceutical market is expected to grow moderately while biologics, generic drugs, and specialty-initiated drugs are projected to increase at double-digit rates. These trends for finished pharmaceuticals are reflected in the global market for APIs, where the merchant generic API market is expected to see strong demand. On a production basis, India and China are forecast to raise their shares of the global generic API market against industry strongholds Italy and Spain. Meanwhile, the US is expected to hold its its position as the leading producer of biotechnology-based APIs in an area traditionally dominated by captive production. And biogenerics or biosimilars gradually reshape the market.

The authors review methods for reducing analysis time and increasing throughput that are reliable and maintain data integrity.

Polysaccharide-based chiral stationary phases have been developed that comprise chiral selectors immobilized on their support rather than being physically coated. These materials are completely solvent stable, thereby increasing selectivity and and enabling the development of new chiral selectors that have been too unstable in a coated form for general use.

The combination of supercritical fluid chromatography with chiral separation media offers several analytival advantages over traditional liquid chromatography techniques.

Ultrahigh pressure liquid chromatography maximizes efficiency, but, as defined by the resolution equation, the stationary phase is still a crucial consideration when attempting to resolve mixtures of compounds.

High performance liquid chromatography has become an efficient technique at the production scale, and simulated moving bed chromatography provides several benefits during processing.

The authors consider the advantages of using rapidly dissolving films to accurately and effectively deliver pharmaceutical ingredients, with an emphasis on the importance of controlling moisture content and drug loading during formulation development.

Company and People Notes: Evotec and Renovis enter agreement, Amgen to lay off 675 workers, more.

The US Food and Drug Administration has denied shipments of active pharmaceutical ingredients manufactured at a production facility of Kunshan Chemical and Pharmaceutical Co. for violation of good manufacturing practices, according to an FDA warning letter issued Sept. 6, 2007.

Company and People Notes: Catalent expands Bolton, UK, warehouse; Biotica appoints Edward E. Hodgkin as CEO and director; more.

Company and People Notes: Baxter and Halozyme Expand Relationship, Crucell Names COO, More.

More than 100 people attended this week’s Regulatory Affairs Conference by the International Pharmaceutical Excipients Council of the Americas to discuss the latest trends and challenges in the excipient supply chain.

Aptuit expands its drug-development capabilities with the formation of Aptuit Laurus to take advantage of the growing pharmaceutical outsourcing market in India.

Researchers forward approaches for catalytic hydroformylation, asymmetric hydrogenation, and biocatalysis to achieve enantioselectivity.

The influence of magnesium stearate (MgSt) on powder lubrication and finished solid-dose properties presents big challenges to drug manufacturers.

This article presents collaborative positions among excipient manufacturers, drug product manufacturers, and members of the US Pharmacopeia on key issues pertaining to the control of pharmaceutical excipients stemming from a recent Pharmaceutical Quality Research Institute workshop.

Fiera Milano Rho Exhibition Centre, Milan, Italy 2–4 October 2007

The recently published Orange Guide 2007 contains significant changes to the GMP requirement placed on pharmaceutical manufacturers, but there have been additional changes to good distribution practice that should not be overlooked.

A new economical method for producing fast-melting lamina-like dosage forms.

The authors discuss how companies facing ever-evolving regulatory requirements can address and assess compliance risk in their operating practices.

This article investigates how the industry can test inhalers in a way that is most representative of typical use.

This article describes how rapidly disintegrating tablets containing a large quantity of an intensely bitter drug were successfully developed with a suitable level of masking, tablet hardness, disintegration property, dissolution profile and mouth feel.

A new Raman spectroscopic method to detect magnesium stearate in powder blends and tablets is described. High-volume pharmaceutical manufacturing requires the use of lubricants to facilitate tablet ejection from compressing machines. However, lubricants may also bring a number of undesired problems that have been widely documented in pharmaceutical scientific literature. New analytical methods are needed to understand lubrication and provide process knowledge in support of FDA's process analytical technology initiative. The detection of magnesium stearate in lactose, mannitol, corn starch and other commercially important excipients is reported. The Raman spectroscopic method has a detection limit of about 0.1% (w/w) based on the 2848 cm-1 band that corresponds to the symmetric stretch of the methylene group in magnesium stearate.

The authors evaluate the scalability of foam-granulation technology using continuous foam addition in high-shear granulation equipment at the laboratory, pilot and manufacturing scales. Immediate- and controlled-release model formulations were used. Continuous and batch addition of foam were compared for the controlled-release model formulation at the manufacturing scale, and physical testing was performed on the granules and finished tablets.

As China emerges as a significant supplier of pharmaceutical ingredients, it must assure other countries of the safety of its excipients.

Identifying polymorphs is a crucial part of the drug-development process as researchers forward select methods to improve detection.

Contract manufacturers and pharmaceutical ingredient suppliers proceed with select investments in biologics manufacturing, small-molecule synthesis, and formulation as the industry prepares for CPhI Worldwide in Milan.

Single-enantiomer drugs represent an increasingly large share of new chemical entities, leading to approaches in asymmetric synthesis.