Excipient liquid

Liquid f omuUatioits poiued on solidiftlng excipients Liquid fomudations poiu ed onto meltable binder Fii stiv et granulation is done 1 ... 

If a liquid dosage form of a medication exists, it would seem rational to use this dosage form for administration through a feeding tube. Although such a decision may decrease the potential for tube clogging, it may in some instances decrease tolerability of the medication administration. Sorbitol is an excipient found in many liquid medications in amounts sufficient to cause diarrhea. If diarrhea secondary to sorbitol in a liquid medication is suspected in a patient on EN, contact with the manufacturer to ascertain sorbitol content may be necessary. 

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. 

For most tablets, it is necessary to overcome the cohesive strength introduced into the mass by compression. It is therefore common practice to incorporate an excipient, called a disintegrant, which induces this process. Several types, acting by different mechanisms, may be distinguished (a) those that enhance the action of capillary forces in producing a rapid uptake of aqueous liquids, (b) those that swell on contact with water, (c) those that release gases to disrupt the tablet... 

Thermal setting formulations in this case, excipients are used which are liquid at filling... 

Another excipient used in feed additive premixes is a diluent used to dilute or standardize activity. Diluents are similar in composition to grain carriers, except the particle size is generally smaller. No attempt is made to absorb the active drug to the individual particles of the diluents. If a liquid is used it is mainly for dust control. A diluent is considered for use when the level of the active ingredient components in the premix approaches or exceeds 50% of the product or when two or more active components vary greatly from one another in density [13]. Examples of diluent materials are ground limestone, sodium sulfate, kaolin, corn cob flour, and ground oyster shells. 

Absorbents are another class of excipient material used in feed additive premixes. They are used when the drug substance is a liquid or is readily soluble in water, oil, or some other solvent. The liquid is sprayed onto the absorbent in a mixer as the mixer is running. Examples of absorbents are vermiculite, Fullers earth, corn cob fractions, and clay. 

The decision to market the product in liquid or powder form is often dictated by how stable the protein is in solution. This, in turn, must be determined experimentally, as there is no way to predict the outcome for any particular protein. Some proteins may remain stable for months (or even years) in solution, particularly if stabilizing excipients are added and the solution is refrigerated. Other proteins, particularly when purified, may retain biological activity for only a matter of hours or days when in aqueous solution. 

The freeze-drying process is initiated by the freezing of the biopharmaceutical product in its final product containers. As the temperature is decreased, ice crystals begin to form and grow. This results in an effective concentration of all the solutes present in the remaining liquid phase, including the protein and all added excipients. For example, the concentration of salts may increase to... 

Rebif is produced via recombinant DNA technology in a CHO cell line. It displays an identical amino acid sequence to that of native human IFN-P-la and, like the native product, is glycosylated. After cell culture the interferon is purified using a series of chromatographic steps (affinity, ion-exchange, gel-filtration and reverse-phase liquid chromatography). It is formulated as a sterile solution in pre-filled syringes and contains mannitol, HSA, sodium acetate, acetic acid and sodium hydroxide as excipients. It is administered subcutaneously three times weekly. 

Phase diagrams are often constructed to provide a visual picture of the existence and extent of the presence of solid and liquid phases in binary, ternary and other mixtures of substances. Phase diagrams are normally two-component (binary) representations but multicomponent phase diagrams can also be constructed. Interactions between active substances and excipients can often be evaluated using phase diagrams. 

Purified drug substances are mixed with excipients into finished dosage forms sohds, liquids, parenterals, inhalants, and ointments and creams, then packaged and labeled and shipped for distribution. 

The extent of revalidation required for formulation changes should be determined on a case-by-case basis. Slight adjustments to the formulation may not require further validation work. This would include an adjustment of the excipient ratios, a change in tablet shape, etc. Specificity and accuracy should be re-evaluated for the inclusion of a new excipient into the formulation (e.g., antioxidants, dyes, preservatives). A change in the formulation such as going from a tablet to a capsule or from a liquid to a solid would mean a significant change to the formulation and complete validation should be performed. 

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. 

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. 

Preformulation testing provides a basic dossier on the compound and plays a significant role in identifying possible problems and suitable approaches to formulation. Such dossiers already exist for the common excipients. The requirement for aqueous solubility is paramount and preformulation can identify salt forms that are appropriate for further development. Stability and solubility studies wiU indicate the feasibility of various types of formulation such as parenteral liquids and their probable shelf lives. Similar information can be garnered for solid products from the solid physical properties. By performing these studies on a series of candidate compounds, the optimum compound can be identified and further biological and chemical studies guided to provide the best results. 

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