protein structure - Articles and news items

Breaking old habits: Moving away from commonly used buffers in pharmaceuticals

Ingredients, Issue 3 2012 / 10 July 2012 / David Sek, Research Scientist, Pfizer

One of the key factors in stabilising proteins is determining the optimal pH and buffer system to provide adequate solubility and stability. Currently, three buffers, citrate, phosphate and acetate, make up the majority of buffers used in parenteral pharmaceuticals approved by the FDA, but less precedented excipients are certainly available to use in commercial dosage forms. A number of alternative buffers have also gone through the approval process to be proven safe, and the use of histidine and tromethamine is becoming increasingly common in parenteral formulations. This article highlights the advantages of some lesser known buffers with the hope that bringing these excipients into the clinic and market more often will help to augment the tools formulators have available in achieving stable protein formulations.

The US Food, Drug and Cosmetic Act of 1938 required manufacturers and pharmaceuticals companies to be responsible for the safety of drug additives / excipients in their products in response to a tragedy where 100 children were killed from the presence of diethylene glycol in an antibacterial product. To help clarify what is needed to establish a new excipient, the FDA released a guidance document in 2005 entitled ‘Nonclinical Studies for the Safety Evaluation of Pharmaceutical Excipients’, outlining the safety studies needed in order to have an excipient approved1,2. Recent articles have called for the need for more alternative excipients for the use in formulations1,3,4.

Figure 1 MD simulation model of the opsin-transducin complex in a POPC lipid bilayer. Opsin and transducin are drawn in ribbon format and post-translational modification on opsin and transducin are represented in space-fill style. Opsin is oriented in the bilayer such that helix 4 (H4) is perpendicular to the plane of the bilayer. The extracellular surface is oriented toward the top of the figure.

Examining receptor activation: New technologies reveal how G protein-coupled receptors recognise ligands and talk to intracellular partners

Drug Targets, Issue 3 2010, Past issues / 24 June 2010 / Thomas P. Sakmar, Laboratory of Molecular Biology & Biochemistry, Rockefeller University

Heptahelical G protein-coupled receptors (GPCRs) are arguably the most important single class of pharmaceutical drug targets in the human genome. According to Overington, of the 266 human targets for approved drugs, a remarkable 27 per cent correspond to rhodopsin-like, or Family A, GPCRs. Despite recent dramatic advances in targeting of kinases, the continued success of monoclonal antibody-based therapeutics and the advent of new drug entities like siRNAs, GPCRs remain the pre-eminent class of drug targets…


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