Stabilizing agents cyclodextrins

A very interesting field in membrane bioreactors is the production of cyclodextrins or oligosaccharides. In general, they have applications in food pharmaceutical, cosmetic agricultural, and plastics industries as emulsifiers, antioxidant, and stabilizing agents. In the food industry cyclodextrins are employed for the preparation of cholesterol-free products. The use of enzymatic membrane reactors to produce... 

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],... 

Ueda, H. Ou, D. Endo, T. Nagase, H. Nagai, T. Evaluation of a sulfobutyl ether p-cyclodextrin as a solubilizing/stabilizing agent for several drugs. In Symposium on Pharmaceutical Applications of Cyclodextrins Lawrence, KS, June 29-July 2, 1997. 

Complexing and chelating agents Cyclodextrins EDTA Salicylates Citric acid Formation of inclusion complexes Increase of stability Increase paracellular transport by Removing calcium ions Widening of tight junctions... 

Brewster ME, Hora MS, Simpkins JW, and Bodor N. Use of 2-Hydroxypropyl-Cyclodextrin as a Solubilizing and Stabilizing Agent for Protein Drugs. Pharm Res 1991 8 792-795. 

The spreading applications of prostanoids-especi-ally that of the prostacyclin, the effective antiplatelet and cytoprotective agent - is limited by their instability To overcome this problem either ne tf, more stable aiialogues are synthetized, or the endogeneous substance is stabilized by cyclodextrin complexation / /. The rates of hydroly-sis of prostacyclin /PGI / and its methyl-ester /PGI Me/ in aqueous solution are significantly retarded by c(-, p-and jj -cyclodextrin /8/ The highest stability constant could be rendered to PGI Me-(S-CD complex ... 

Cyclodextrins have had valuable industrial uses for a considerable time, particularly as agents to bind or release volatile molecules. Accurate predictions concerning the selectivity and stability of cyclodextrin-guest complexes are therefore of considerable interest both academically and practically." MD was used to simulate cyclodextrin hydrates" as a test of the applicability of the GROMOS program package to systems beyond proteins and nucleic acids. Other early MD simulations focused on interactions with guests such as enantiomers of methyl-2-chloropropionate. Comparisons between calculated thermodynamic properties for complexes formed by O -cyclodextrin with para-substituted phenols and the results of MM simulations led to improvements in force fields that described the interactions. MM2 simulations were used to support NMR data for the -cyclodextrin inclusion complex with benzoic acid. " The well-known catalytic effect of cyclodextrins has been modeled. For example, the relative rate increase of hydrolysis of S over R phenyl ester stereoisomers in the presence of -cyclodextrin... 

In order to keep the mild conditions, hydroxycarbonylation has been performed in biphasic media, maintaining the catalyst in the aqueous phase thanks to water-soluble mono- or diphosphine ligands. In the presence of the sodium salt of trisulfonated triphenylphosphine (TPPTS), palladium was shown to carbonylate efficiently acrylic ester [19], propene and light alkenes [20,21] in acidic media. For heavy alkenes the reduced activity due to the mass transfer problems between the aqueous and organic phases can be overcome by introducing an inverse phase transfer agent, and particularly dimeihyl-/-i-cyclodextrin [22,23]. Moreover, a dicationic palladium center coordinated by the bidentate diphosphine ligand 2,7-bis(sulfonato)xantphos (Fig. 2) catalyzes, in the presence of tolylsulfonic acid for stability reasons, the hydroxycarbonylation of ethylene, propene and styrene and provides a ca. 0.34 0.66 molar ratio for the two linear and branched acids [24],... 

The stability of orange peel oil depends on the selection of the encapsulation process and the encapsulating agent. The results of this study indicated that the differences in shelf life were greatly accentuated at higher temperatures. The shelf life of the spray dried products ranged from 5-35 days compared to the extrusion and beta-cyclodextrin products which were still acceptable after 180 days at 50 C. 

Takahashi, T., et al. 1986. Stabilization of AD-1590, a non-steroidal antiinflammatory agent, in suppository bases by (3-cyclodextrin complexation. Chem Pharm Bull 34 1770. 

On the other hand, many excipients can act to chemically stabilize an API in the solid state and in solid dosage forms. The most common class of stabilizing excipients is cyclodextrins (36). Cyclodextrins can envelop the API in their hydrophobic cavities and shield it from common degradation reactions such as hydrolysis, oxidation, or photodegradation. Some excipients or additives may also act as complexing agents that provide hydrolytic (37) and oxidative (38) stabilization. Many excipients, such as cyclodextrins, dyes, and colored additives, are capable of providing extensive photostabilization in the solid state (39-41). 

Ono, N. Hirayama, F. Arima, H. Uekama, K. Determination of stability constant of P-cyclodextrin complexes using the membrane permeation technique and the permeation behavior of drug-competing agent-P-cyclodextrin ternary systems. Eur. J. Pharm. Sci. 1999, 8 (2), 133-139. 

Sulfobutylether P-cyclodextrin can form noncovalent complexes with many types of compounds including small organic molecules, peptides, and proteins. It can also enhance their solubility and stability in water. The first application of sulfobutylether P-cyclodextrin was in injectable preparations it can also be used in oral solid and liquid dosage forms, and ophthalmic, inhalation, and intranasal formulations. Sulfobutylether P-cyclodextrin can function as an osmotic agent and/or a solubilizer for controlled-release delivery, and has antimicrobial preservative properties when present at sufficient concentrations. 

---