Excipient chemical stability

There are two primary questions that a formulator will often ask regarding a biopharmaceutical. First and foremost, what excipients (inactive ingredients like chemical stabilizers, buffers, and toxicifiers) and solution conditions (i.e., pH, temperature) offer the greatest stabilization Second, how long will the chosen... 

For nebulizer and other aqueous aerosol products that use suspension systems, excipients are used to influence particle physical and chemical stability (e.g., microcrystalline cellulose for nasal sprays). The suitability of the physicochemical properties of these critical excipients should be thoroughly investigated and documented (12). Far more excipients have been included in formulations designed for nasal administration (Table 4). 

Once good physical stability of an emulsion is insured, its commercialization mandates chemical stability of the incorporated drug and other essential components for at least 18 months. Key factors that affect the chemical stability of pharmaceutical emulsions include drug stability in oil, drug stability in aqueous media, drug concentration in oil and emulsion, phase volume ratio, droplet size, presence of excipients, and presence of air and/or peroxide radicals. As mentioned earlier, choice of appropriate antioxidant is important. 

Radomska-Soukharev, A. and R. H. Mueller. 2006. Chemical stability of lipid excipients in SLN-production of test formulations, characterization and short-term stabflH armazid51 425-430. 

Minimally, one should have a brief foreknowledge of the thermal and thermal/humidity solid-state stability of the API prior to initiation of excipient compatibility studies. These protocols should include investigation of stability at various temperature and humidity conditions and should always include information about both chemical stability and physical-form integrity of the API. Thermal and thermal moisture-induced solid-state chemical reactions are well known (5), with hydrolysis and oxidation being the most prevalent mechanisms of decay. Changes in physical form with thermal and... 

On the other hand, many excipients can act to chemically stabilize an API in the solid state and in solid dosage forms. The most common class of stabilizing excipients is cyclodextrins (36). Cyclodextrins can envelop the API in their hydrophobic cavities and shield it from common degradation reactions such as hydrolysis, oxidation, or photodegradation. Some excipients or additives may also act as complexing agents that provide hydrolytic (37) and oxidative (38) stabilization. Many excipients, such as cyclodextrins, dyes, and colored additives, are capable of providing extensive photostabilization in the solid state (39-41). 

However, for low-dose chug products, impurities from excipients can be more problematic for causing chemical stability issues with a drug product. Several commonly used excipients (including povidone, PEG400, polysorbate 80, and hydroxypropyl... 

If a compound is known to have chemical stability issues and is going to be administered in low dose, the best prevention is to ensure the highest degree of crystallinity of the bulk active ingredient delivered to the formulation and maintain it in the state with the highest ratio of drug to excipient possible. 

Cyclodextrins (CDs) have a wide range of application in the pharmaceutical field due to their unique structure, which allows them to include hydrophobic molecules in their apolar cavity and to mask the physicochemical properties of the included molecule. This results in the enhancement of drug bioavailability by improving aqueous solubility and the physical and chemical stability of the drug, masking undesired side effects such as irritation, taste, or odor, and overcoming compatibility problems or interactions between drugs and excipients. 

In an earlier section, the potential for a water-soluble substance to deliquesce was discussed. The emphasis here is on less obvious effects of moisture on solid dosage forms, and three associated areas that link to information presented earlier in this article are discussed 1) moisture-induced changes in the state of the solid 2) the effect of moisture on the performance of excipients in the manufacture of compressed tablets and 3) the chemical stability of bioactive agents alone and in combination with excipients. 

---