Excipient surfactant excipients

Ophthalmic ointments usually contain petrolatum as the base. The petrolatum is sterilized by dry heat and combined with the sterile dmg powder under aseptic conditions. Ophthalmic suspensions contain very fine (- 10 ji) particle sized soHds suspended in an aqueous vehicle. The vehicle is adjusted to isotonicity and viscosity-increasing excipients, chelating agents, and surfactants also may be needed. The aqueous vehicle in these cases is generally autoclaved and mixed with sterile dmg powder asceptically (30). 

JTH Ong, ZT Chowhan, GJ Samuels. Drug-excipient interactions resulting from powder mixing VI. Role of various surfactants. Int J Pharm 96 231-242, 1993. 

There are two EPARs for eyedrops. Specific issues considered for these include container composition and tamper evidence, the optimization of the formulation and manufacture, preservative and preservation issues, and justification for the use of nonterminal sterilization processes. Many of the points concerning active ingredients and excipients are similar to those discussed above. Changes in formulation during the development process (e.g., for carbomers or surfactants) are mentioned. Particle size controls for suspension products are discussed. 

Anderberg, E. K., C. Nystrom, and P. Artursson. Epithelial transport of drugs in cell culture. VII Effects of pharmaceutical surfactant excipients and bile adds on transepithelial permeability in monolayers of human intestinal epithelial (Caco-2) cells,... 

The use of flow cells may generate variability in absorbance readings. Air bubbles can become caught in the cell, either introduced via a water source containing bubbles or by air entering inadvertently into poorly secured sample lines. Flow rate and dwell time should be evaluated so that the absorbance reading can be determined to have reached a steady plateau. Cells need to be cleaned frequently to avoid build up of drug, excipient, surfactant, or buffer salts from the dissolution medium. 

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... 

A pulsed system, called Time-Clock System, has been developed. It comprises a solid dosage form coated with a hydrophobie surfactant layer to which a water-soluble polymer is attached to improve adhesion to the core [66]. The thickness of the outer layer determines the time required to disperse in an aqueous environment. Following the dispersion of the outer layer, the eore becomes available for dispersion. An advantage is that eommon pharmaceutical excipients can be used to manufacture this system. Studies performed on human volunteers showed that the lag time was not affeeted by gastrie residence time. Furthermore, the dispersion of the hydrophobic film was not influenced by the presence of intestinal digestive enzymes or by the mechanieal aetion of the stomach. 

Formulation of dry powders for inhalation must rely on a very short list of excipients to fulfill the customary roles of diluent, stabilizer, solubilizer, processing aid, and property modifier (e.g., flow enhancer). In the United States, only a few materials are approved for use in inhalation products, and of those (e.g., propellants, surfactants) many are of little help in dry powder formulation. 

Drug molecules with amphiphilic character may form lyotropic mesophases, and amphiphilic excipients in drug formulations also form lyotropic liquid crystals. Especially surfactants, which are commonly used as emulsifiers in dermal formulations, associate to micelles after dissolution in a solvent. With increasing concentration of these micelles the probability of interaction between these micelles increases and thus the formation of liquid crystals. 

One of the major questions in relation to absorption enhancers such as surfactants or sustained release products is their safety. Whether damage to lung tissue is caused by the different excipients is not yet clear. The results obtained so far are not very promising for substances like surfactants [39]. What the effects of repetitive administration of insoluble or slowly (bio)degrading particles might be, remains to be estabhshed. 

Since surface active betaine esters can be degraded under mild conditions and the hydrolysis products, i.e., the amino acid betaine and a long-chain alcohol can be expected to be less toxic than the intact surfactant, these am-phiphiles are interesting candidates for use in applications where surfactant toxicity is an issue. Surface active betaine esters have been evaluated as temporary bactericides [34] and have been studied as potential candidates for use as pharmaceutical excipients (pharmaceutical helper molecules) [30]. 

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. 

Additives are all formulation constituents other than the active ingredient. Although additives could be classified into excipients and vehicles (excipients for solid preparations and vehicles for liquid ones), there are several other agents used in pharmaceutical formulations with specific functions such as preservatives, sweeteners, coatings, colorants, antioxidants, surfactants, emulsifying agents, and flavors. Since they comprise a vast amount of products, this section will deal with additives for compounding pharmaceutical products for internal use only [17,18]. 

Additionally, the stability of dyes in solution can be dependent upon the specific excipients used in the formulation. For example, FD C Blue 2 was found to fade more rapidly in the presence of several sugars (sorbitol, mannitol, dextrose, sucrose, and lactose) and that the nonionic surfactant Pluronic F-68 promoted the fading of FD C Blue 2. The combination of coloring agents can lead to complications... 

Various excipients have been used as solubilizers for BCS class II and class IV drugs. Cyclodextrins provide a prime example of the use of excipients as solubilizers, and have been discussed in detail in a separate chapter. Various surfactants have also been used to create emulsion-/microemulsion-type formulations. These have been discussed in a separate chapter as well. 

Therapeutic group Drug Surfactants/ excipients Propellant system Formulation type Particle size estimate (pm) References... 

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