Excipients volatile

Flavoring agents proper are commonly volatile oils that have been dissolved in alcohol and sprayed onto the dried granules or have simply been adsorbed onto another excipient (e.g., talc). They are added immediately prior to compression to avoid loss through volatilization. In some cases they may even have some lubricating activity. If the oil normally contains ter-penes, a low terpene grade is better so as to avoid possible deterioration in taste due to terpene oxidation... 

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. 

Characterisation of volatile oils (which may be used as excipients in formulations), proprietary cough mixtures and tonics, and fatty acids in fixed oils. 

Residual solvents are organic volatile chemicals that remain in active substances, excipients, and other pharmaceutical products after processing. In spite of their toxic properties, solvents play an important role in the production of pharmaceuticals, during the synthesis, separation, or purification, and their use cannot be avoided. Solvents in this category do not include those used as excipients. 

Formaldehyde, along with other short-chain aldehydes such as acetaldehyde, is a low molecular weight, volatile, reactive contaminant that can be present at low levels from a variety of sources (e.g., excipients such as polyethylene oxide, polyethylene glycol (64,65), or from carbohydrate degradation (66), solvent contamination (51), packaging materials (52), etc.). Formaldehyde is known to react with amines (Fig. 33) to form a reactive N-hydroxymethyl compound (a hemiaminal) that can further react with other nucleophiles. Reaction of formaldehyde with amino acids (67) can cause... 

How is the book arranged In the first few chapters we examine the properties of dmgs and excipients in the solid state and in solution. Gases also are treated because of their importance in the design and use of therapeutic pressurised aerosols, which until recently have been derived from chlorinated fluorocarbons (CFCs), but now are based on volatile fluorinated hydrocarbons (HFAs). 

In particular, the propellant-driven metered-dose inhalers release the aerosol cloud at the very high velocity caused by the pressure of the propellant. The open-mouth technique of inhalation [79] helps to slow down the droplets (and to evaporate the volatile excipients). An even more effective solution is to use spacer devices [4,79-87], in which the aerosol cloud can slowed down, the volatile constituents can evaporate, and any large particles will sediment out. Moreover, the patient can then inhale the remaining aerosol under optimal conditions for pulmonary delivery [4,8,56,79], that is, with a slow inspiratory flow rate. 

An additional broad area of utilization of GC is the determination of residual solvents (organic volatile impurities). The solvents allowed for use in the synthesis and manufacture and their respective residual limits have been addressed by the ICH. Tests for residual solvents should be conducted whenever production or purification processes may result in the presence of such solvents. This mandates that residual solvents be determined in drug substances. For drug products, residual solvent levels may be calculated from the levels in the ingredients used to produce the drug product unless class 1 (to be avoided) or class 2 (to be limited) solvents are used in the manufacture of the drug substance, excipients, or drug product. ... 

This guideline was drafted as a joint working group exercise between experts from both the analytical chemistry and the toxicology fields. Residual solvents in pharmaceuticals are defined as the organic volatile chemicals that are used or produced in the manufacture of drug substances or excipients or in the preparation of drug products. 

Claims have been made that the TBA does not enter into the product glassy phase.It has, however, also been reported that some TBA is indeed incorporated into the freeze-concentrate. If true, this might raise regulatory problems with pharmaceutical product registration. It is also not yet clear whether at temperatures in the region of Tg, the effect of TBA is unique. For instance, with sucrose-water systems, the presence of a volatile buffer salt (ammonium bicarbonate, acetate, formate) has a more marked effect on the sublimation rate than has TBA. On the other hand, with PVP-water systems, TBA is superior in enhancing the sublimation rate. It thus appears that the choice of excipient can also affect the drying rate. 

---