Surfactants drug stability

Buffers can also be provided in parenteral formulations to ensure the required pH needed for solubility and/or stability considerations. Other excipients included in parenteral products are preservatives (e.g., benzyl alcohol, p-hydroxybenzoate esters, and phenol), antioxidants (e.g., ascorbic acid, sodium bisulfite, sodium metabisulfite, cysteine, and butyl hydroxy anisole), surfactants (e.g., polyoxyethylene sorbitan monooleate), and emulsifying agents (e.g., polysorbates). An inert gas (such as nitrogen) can also be used to enhance drug stability. Stability and solubility can also be enhanced by the addition of complexation and chelating agents such as the ethylenediaminetetraacetic acid salts. For a more detailed list of approved excipients in parenteral products, the reader should consult the monographs within the USP. 

Eccleston GM, Beattie L. Microstructural changes during the storage of systems containing cetostearyl alcohol polyoxyethylene alkyl ether surfactants. In Rubinstein MH, ed. Pharmaceutical Technology Drug Stability. Chichester Ellis Horwood, 1989 76-87. 

The main formulation challenge with HFA pMDI has been the poor solubility of the surfactants that were used in CFC products. Most pMDI formulations are suspensions of fine powder in propellant, and in order to obtain acceptable dose uniformity these suspensions usually require surfactants to stabilize them. The inability to use conventional surfactants has therefore led to a range of diverse formulation approaches. These encompass drug solubilization using cosolvents (Qvar is an example), new surfactants, coating particles with surfactant, and particle engineering (Fig. 3). However, as is the case with most... 

Nanosuspensions consist of the pure poorly water-soluble drug without any matrix material suspended in dispersion. It is sub-micron colloidal dispersion of pure particles of drug stabilized by surfactants. By formulating nanosuspensions, problems associated with the delivery of poorly water-soluble drugs and poorly water-soluble and lipid-soluble drugs can be solved. Nanosuspensions differ from nanoparticles, " which are polymeric colloidal carriers of drugs (nanospheres and nanocapsules), and from solid-lipid nanoparticles, which are lipidic carriers of drug. 

Choudhary G., Kumar J., Waha S., Parsad R., Parmar B.S., Development of controlled release formulations of carbofuran and evaluation of their efficacy against Meloidogyne incognita, J. Agric. Food Chem., 54(13), 2006,4727-4733. Dhanorkar V.T., Gogte B.B., Dorle A.K., Formation and stability studies of multiple (w/o/w) emulsions prepared with newly synthesized rosin-based polymeric surfactants, Drug Dev. Ind. Pharm., 27(6), 2001, 591-598. 

Paclitaxel ASD ASD of paclitaxel was prepared with SAS using series of polymers and surfactant as stabilizers (Woo et al. 2006). The drug, polymer, and stabilizer were dissolved in an organic solvent such as ethanol and dichloromethane. This solution was then sprayed into a vessel containing SCF, to produce a highly uniform, nanoscale ASD. The solubility of the paclitaxel solid dispersion prepared by the SAS process was significantly higher than the untreated paclitaxel. 

In nanoprecipitation, the polymer and the drug to be encapsulated are dissolved in an organic solvent miscible with water. This solution is then added dropwise to an aqueous solution of surfactants or stabilizers to form a stable suspension. Appropriate mixing, generally under turbulent conditions, and rapid diffusion of the solvent in the bulk phase create a suspension of polymer NPs that encapsulates the drug that is directly mixed in the organic phase. The most-used solvents are dimethylformamide and dimethyl sulfoxide, both of which are cytotoxic, so a procedure to remove the solvent is required after NP synthesis. This removal is usually obtained by dialysis. 

The effectiveness of a surfactant to stabilize a co-crystal or attain a CSC is determined by the relative magnitude of drug and co-former solubilization by micelles, and As illustrated in Figure 11.9, the greater the drug... 

While most vesicles are formed from double-tail amphiphiles such as lipids, they can also be made from some single chain fatty acids [73], surfactant-cosurfactant mixtures [71], and bola (two-headed) amphiphiles [74]. In addition to the more common spherical shells, tubular vesicles have been observed in DMPC-alcohol mixtures [70]. Polymerizable lipids allow photo- or chemical polymerization that can sometimes stabilize the vesicle [65] however, the structural change in the bilayer on polymerization can cause giant vesicles to bud into smaller shells [76]. Multivesicular liposomes are collections of hundreds of bilayer enclosed water-filled compartments that are suitable for localized drug delivery [77]. The structures of these water-in-water vesicles resemble those of foams (see Section XIV-7) with the polyhedral structure persisting down to molecular dimensions as shown in Fig. XV-11. 

B Lundberg. Preparation of drug-carrier emulsions stabilized with phosphatidylcholine-surfactant mixtures. J Pharm Sci 83(1) 72—75, 1994. 

A cosolvent, typically ethanol, may be used to bring drug into solution. A small number of surfactants (sorbitan trioleate, oleic acid, and lecithin) may be dispersed in propellant systems and can aid in suspension stability and in valve lubrication. 

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