Excipients liquid drug formulations

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. 

It should again be emphasized that at the onset of a new drug program, there are only small amounts of drug substance at hand. One of the first tasks for the preformulation scientist is to establish the framework within which the first clinical batches can be formulated. To this end it is important to know with which common excipients the drug is compatible. Below, the distinction will be made between solid and liquid dosage forms. 

After water, ethanol is most commonly used in the formulation of oral liquids and is not without risk of acute overdose or chronic intoxication in children. There are still many extemporaneous and commercial preparations containing ethanol as co-solvents administered to children. Adverse effects to the central nervous system because of high blood-brain barrier permeability in children are reported, along with drug interactions linked with acute or chronic exposure. In the USA, the limits are set to a maximum of 10% alcohol in products for 12 year olds and over, a maximum of 5 % alcohol in products intended for children aged 6-12 years and less than 0.5% alcohol content in products intended for children under 6 years of age. Nevertheless, further longterm research is needed to evaluate safety when this excipient is present in the drug formulation. 

The therapy of a chronic disease requires repeated drug dosing. In the case of a short biological half-life, the drug has to be administered up to several times daily within short intervals. To reduce the application frequency, sustained formulations have been developed. For this purpose liquid crystalline excipients are appropriate candidates, because in a liquid crystalline vehicle the drug diffusion is reduced by a factor of 10 to 1000 in comparison with a liquid vehicle such as a solution [35-37]. The factor depends on liquid crystal. 

A variety of different artificial sweeteners have been approved for use in oral liquid dosage forms by the FDA. One general characteristic for artificial sweeteners is their very high sweetness compare to sucrose. This also results in a much lower concentration needed in the formulation, which can lower the cost and/or risk of incompatibility with the drug or other excipients. Additionally, a sugar-free formulation... 

It is essential to understand how and when the polymorphs of drug substance in oral liquid dosage forms and suspensions can be controlled. One approach to study this phenomenon is to seed the formulation with a small amount of a known polymorphic crystal (other than what is used for the product), which is a common practice to rapidly determine what effect this may have on long-term storage. From these types of studies, the appropriate excipients can be used to preserve the specific polymorphic form desired. However, even when the drug in its crystalline form is studied extensively, there are cases when a previously unknown polymorph may be formed in solution and lead to precipitation (14). 

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