Drug-amino acid formulations

The essential distinction between the approaches used to formulate and evaluate proteins, compared with conventional low molecular weight drugs, lies in the need to maintain several levels of protein structure and the unique chemical and physical properties that these higher-order structures convey. Proteins are condensation polymers of amino acids, joined by peptide bonds. The levels of protein architecture are typically described in terms of the four orders of structure [23,24] depicted in Fig. 2. The primary structure refers to the sequence of amino acids and the location of any disulfide bonds. Secondary structure is derived from the steric relations of amino acid residues that are close to one another. The alpha-helix and beta-pleated sheet are examples of periodic secondary structure. Tertiary... 

Muranishi, S., Absorption enhancers, Crit. Rev. Ther. Drug Carrier Syst., 7 1-33 (1990). Nishihata, T., Kamikawa, K., Takahata, H., and Kamada, A., Enhanced intestinal absorption of amino aeids and amino acid-like drug by possible formulation of anamine in administered solution by the presenee of ethylacetoacetate, J. Pharmacobiodyn., 7 143-150 (1984). 

Selective detectors tend to be employed where the analyte is present in small amounts in a complex matrix such as in bioanalytical procedures where components extracted from the biological matrix along with the analyte can cause interference. Some formulated compounds have only very poor chromophores - these include sugars, lipids, surfactants, amino acids and some classes of drugs, e.g. a number of anticholinergic drugs lack chromophores. In these cases an alternative to UV detection has to be employed. 

Apart from pharmaceuticals, peptides are also used for diagnostics and vaccines. More than 40 peptides are in commercial use today. A dozen of them is shown in Table 3.1. As shown in column 3 of the table, the number of amino acids that make up a specihc peptide varies widely. At the low end there are dipeptides, like the blockbuster antihypertensive drug enalapril and the artihcial sweetener Aspartame (not shown in the table). In terms of volumes produced, there are by far the most important product group. At the high end there is the anticoagulant Hirudin, which is composed of 65 amino acids. Sales of synthetic peptides are estimated at 4 billion as formulated drugs (resp. 300- 400 million as APIs). 

The diets did not claim to be organic but could be formulated to organic standards quite readily. Surprisingly the diets contained the anticoccidial drug salinomycin and also the amino acid pure methionine, suggesting that these additives are permitted in the Label Rouge system. 

One of the critical factors in excipient selection and concentration is the effect on preferential hydration of the biopharmaceutical product [53, 54], Preferential hydration refers to the hydration layers on the outer surface of the protein and can be utilized to thermodynamically explain both stability enhancement and denatur-ation. Typical excipients used in protein formulations include albumin, amino acids, carbohydrates, chelating and reducing agents, cyclodextrins, polyhydric alcohols, polyethylene glycol, salts, and surfactants. Several of these excipients increase the preferential hydration of the protein and thus enhance its stability. Cosolvents need to be added in a concentration that will ensure their exclusion from the protein surface and enhance stability [54], A more comprehensive review of excipients utilized for biopharmaceutical drug products is available elsewhere [48],... 

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