Excipient Molecular Weights

The second example is the SE-HPLC analysis of recombinant hGH. In this example, SE-HPLC is used for both a purity and a protein concentration method for bulk and formulated finished products. This method selectively separates both low molecular weight excipient materials and high molecular weight dimer and aggregate forms of hGH from monomeric hGH, as shown... 

H-bonding potential Molecular weight/size PSA Intestinal metabolism Transport mechanisms Native surfactants Intestinal secretions, e.g. mucous, enzymes Intestinal blood/lymph flow Excipient effects... 

Protein drugs have been formulated with excipients intended to stabilize the protein in the milieu of the pharmaceutical product. It has long been known that a variety of low molecular weight compounds have the effect of preserving the activity of proteins and enzymes in solution. These include simple salts, buffer salts and polyhydroxylated compounds such as glycerol, mannitol, sucrose and polyethylene glycols. Certain biocompatible polymers have also been applied for this purpose such as polysaccharides and synthetic polymers such as polyvinyl pyrrolidone and even nonionic surfactants. 

Polyethylene glycol (PEG), a hygroscopic polymer, was the first molecule to be considered for modifying the surface of proteins. It has proved to be very successful. PEG, available in molecular weights ranging from a few hundred to several thousand daltons, have been used as parenteral excipients for decades with proven clinical safety. 

Formaldehyde, along with other short-chain aldehydes such as acetaldehyde, is a low molecular weight, volatile, reactive contaminant that can be present at low levels from a variety of sources (e.g., excipients such as polyethylene oxide, polyethylene glycol (64,65), or from carbohydrate degradation (66), solvent contamination (51), packaging materials (52), etc.). Formaldehyde is known to react with amines (Fig. 33) to form a reactive N-hydroxymethyl compound (a hemiaminal) that can further react with other nucleophiles. Reaction of formaldehyde with amino acids (67) can cause... 

Today, there is more emphasis on quality of excipients. For example, some inherent quality variability may occur in the natural products magnesium stearate and sodium starch glycolate. What is the impact of the variability of these excipients on product quality attributes Also, excipient viscosity, molecular weight, and particle size relative to API particle size could be critical factors to some formulations. An optimal dissolution method can only be developed on the basis of knowledge of the dmg product. 

Several polymers were found to fit all or most of the above criteria and were used to prepare the carrier films. Many polymers have been used for this purpose, viz., ethyl cellulose, poly(y-benzyl glutamate), poly(vinyl acetate), cellulose acetate phthalate, and the copolymer of methyl vinyl ether with maleic anhydride. In addition to the base polymers, plasticizers were often needed to impart a suitable degree of flexibility. Plasticizers, which are found to be compatible with polymeric materials include, acetylated monoglycerides, esters of phthalic acid such as dibutyl tartarate, etc. An excipient was usually incorporated into the matrix of the carrier films. The excipients used were water-soluble materials, which are capable of creating channels in the polymer matrix and facilitate diffusion of the drug. PEGs of different molecular weights were used for this purpose. 

---