Excipients typical

Powders are porous materials and their bulk and relative densities can change with consolidation (6). However, a powder s true density is the density of its solid phase only and thus is independent of the state of consolidation. The true density of organic excipients typically ranges from 1.0 to 1.6g/cm3 while inorganic excipients (e.g., calcium phosphate) show values greater than 2g/cm3. True density is used to determine powder or compact solid fraction (SF) (see below) and it may be a consideration when selecting excipients if segregation is a concern. True density is often determined by gas pycnometry. 

Ascending the level of complexity of lipid-based formulations are those that contain mixtures of three excipients. Typical examples of such combinations include 1) medium-chain triglycerides, PEG, and PG 2) TPGS, PEG 400, and PG 3) oleic acid, cremophor EL, and ethanol or PG 4) Polysorbate 20, PEG... 

The basic approach is that of mixing two components (drug and excipient) typically in a 50/50 mix and then performing a DSC scan. The melting profile of the two individual components is then compared with the scan of the mixture. Ideally, if no interaction occurs then the mixture should show equivalent transitions to that of the individual components. If it does not, some interaction is indicated. 

Characterisation Typical data that may be provided to describe the physical and chemical characteristics of the drug substance are shown in Figure 6.3. The description of the drug product should include the recipe detailing all the other ingredients (excipients) that are used to formulate the final product. It is vital to provide adequate data on the dissolution behaviour of the drug product, as the reviewer may wish to tie this in with pharmacokinetic or bioavailability data submitted in the other modules. 

Incompatibilities have also been observed in solid dosage forms. A typical tablet contain binders, disin-tegrants, lubricants and fillers. Compatibility screening for a new drug should consider two or more excipients from each class. Serajuddin et al. have developed a drug-excipient compatibility screening model to predict interactions of drug substances with excipients [49],... 

The topics of polymorphism and pseudopolymorphism dominate the majority of publications that deal with utilizing infrared spectroscopy for the physical characterization of pharmaceutical solids. Typically, in each of the publications, IR spectroscopy is only one technique used to characterize the various physical forms. It is important to realize that a multidisciplinary approach must be taken for the complete physical characterization of a pharmaceutical solid. Besides polymorphism, mid- and near-IR have been utilized for identity testing at the bulk and formulated product level, contaminant analysis, and drug-excipient interactions. A number of these applications will be highlighted within the next few sections. 

Table 8 Typical Properties of Some Common Drugs and Excipients Determined at a Compact Solid fraction of 0.8 to 0.9...

The product is presented in lyophilized format and contains sodium phosphate, sucrose and polysorbate as excipients. It is usually administered as once-weekly s.c. injections, typically for periods of 6 months. 

The original applications of NIR were in the food and agricultural industries where the routine determination of the moisture content of foodstuffs, the protein content of grain and the fat content of edible oils and meats at the 1% level and above are typical examples. The range of industries now using the technique is much wider and includes pharmaceutical, polymer, adhesives and textile companies. The first in particular are employing NIR spectrometry for the quality control of raw materials and intermediates and to check on actives and excipients in formulated products. Figure 9.26(b) demonstrates that even subtle differences between the NIR spectra of enantiomers can be detected. 

Tablet excipient interactions are occasionally observed when evaluating a drug product for purity. Since there are many excipients in a typical pharmaceutical tablet, known bands need to be identified to make it easier to evaluate for degradation products. Unfortunately, occasionally an inert excipient may react with a derivatizing agent used in TLC making this entity appear as a band that now needs to be identified. In Fig. 13.33, a placebo tablet, an extracted tablet, a handmade tablet blend of all components, and the drug substance standard are all applied to the same HPTLC plate and developed. These results alert the analyst to any excipients that may interfere in the evaluation of the tablet for purity. In this case, the only bands observed in the tablet blend and extracted tablet are the same bands seen in the tablet blend.

Figure 8 shows a typical F4PLC chromatogram of the tablet extract illustrating the complexity of the sample, which contains numerous natural components, excipients and additives. During the SP method development, it was found that extraction with a neutral aqueous buffer was problematic due the loss of one of the active ingredients by hydrolysis. The use of the PTFE filter was also important because this hydrolysis product, which is highly hydrophobic, was absorbed by nylon filters under the filtration conditions. 

The candidate method is used to support drug synthesis, excipient compatibility, and ultimately to evaluate candidate formulations. Such support typically involves analyses of stressed materials to identify degradation trends. These studies are conducted in the solid state by exposing the DS and DP to relative humidity, temperature, light, and oxidizing... 

A preservative is a substance that prevents or inhibits microbial growth and extends the shelf life of the drug products. In most pharmaceutical drug products, only a few compounds are typically selected as preservatives. For efficiency, a generic method should be developed for the types of preservatives that are more commonly used. For example, butylated hydroxytoluene (BHT) is an antioxidant commonly used in many solid dosage formulations to retard oxidative degradation of the excipients. 

Several dosage forms carry an increased risk of degradation or adjunct formation. Products such as injections and aerosols are more likely to interact with volatiles or extractables from packaging and closure systems. Tablets have the potential to form adjuncts with excipients (specifically, lactose has been shown to form adjuncts in tablets). Non-CFC propellants in aerosols have a large number of impurities that typically do not interact with drug substances, but the potential for these interactions does still exist. Creams, ointments, lotions, and other such products will each have specific interactions that should be considered while evaluating the impurity profile of a drug product. 

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