Formulation stability requirements

Most proteins are not sufficiently stable in aqueous solution to allow formulation as a sterile solution. Instead, the protein is freeze-dried and reconstituted before use. Development of a freeze-dried protein formulation often requires special attention to the details of the freezing process (potential pH shifts and ionic strength increase with freezing) as well as to potential loss of activity with drying. Formulation additives, such as sugars and polyhydroxy compounds, are often useful as cryoprotectants and lyoprotectants. Residual moisture may also be critical to the stability of the dried preparation [33],... 

Although the physicochemical stability of these lipid-based formulations may be well characterized, the impact on the physiological factors of drug adsorption and metabolism can vary dramatically. As such, lipid-based formulations may require more extensive BE/BA studies than simple oral liquids such as solutions or syrups. 

The choice of electrode material is more critical in LCEC than in the usual electroanalytical experiment, primarily due to the mechanical ruggedness and long-term stability required. Carbon paste (an admixture of graphite powder and a dielectric material) remains a useful choice as an electrode material for LCEC. While carbon paste can be used in nonaqueous solvents if formulated... 

Development studies, summarized within a distinct report on the physiochemical aspects, drug substance attributes, and finished product characteristics, become critical parts of the validation package. Such data is also valuable for future integration into a manufacturing operation. This includes the scientific rationale for formulating and bulk-handling procedures, lyophilization processing parameters, finished product analysis, and stability requirements. 

So far, most interest has been focused on the dinitramide salts of nitrogen bases, particularly ADN. ADN starts to decompose slowly at 85°C. A vacuum stability test showed that 0.88 ml of gas per gram were evolved from a sample over a period of 40 hours. Despite this instability, it has been demonstrated that ADN-based formulations fulfill the military stability requirements at 80°C. However it is unlikely that ADN could be used in any military or commercial applications above its melting point. The rate of decomposition and its autocatalytic behavior conflict with safety considerations. 

Starch choice is affected by formulation. Increased competition for water (e.g. by sugars) will require a less crosslinked or more stabilized starch to be used. Acidic formulations will require more crosslinking. The manner in which the food is to be distributed is also important regarding the base choice and amount of stabilization. Frozen or refrigerated distribution requires greater monosubstitution for texture and appearance stabilization. The following overview of starch use in specific applications illustrates how food starches are chosen. 

Tn developing any new pesticide formulation many factors must be - considered physical form, method of application, pests to be controlled, compatibility with other toxicants, and many more that are too numerous to mention. For a formulation to be useful, however, it must meet certain minimum chemical and physical stability requirements. Guthion (0,0-dimethyl S-[4-oxo-l,2,3-benzotriazin-3 (4H) -ylmethyl] phosphorothioate), which has been used for a number of years to control many insects, was the toxicant used in this investigation. 

A1203 catalysts originates from interactions other than those existing in the binary system Cu/ZnO. The structural promotion by alumina is a very significant factor in the formulation of industrial catalysts, however, as it imparts chemical and mechanical stability required for a long-lived catalyst in large-scale reactors. 

One of the means used to modify monomers and polyester acrylates further is to amine modify them. This is normally done using a Michael addition reaction between the acrylate and an amine. The benefits of amine modification are normally seen with increased cure speed since this will tend to overcome the effects of oxygen inhibition in the cure process. Amine oligomers and synergists can also be low viscosity and give improved flexibility to a film. One disadvantage of these materials maybe that perhaps they do not possess the stability required of UV inkjet ink formulations. They are also very prone to yellowing and are unstable with some forms of adhesion promoters. 

By the time an active pharmaceutical ingredient (API) is made available to an analytical chemist in the formulation development group, most or all of the physical characteristics of an API has already been studied and the information should be available in some sort of a report from the drug substance group or preformulation group. Some of the key parameters that an analytical chemist in formulation development requires from such a report are the solubility and solution stability. 

There are three types of stability testing (technical, clinical, and registration) performed during formulation development. Requirements of a stability program increases going from technical to clinical to registration. The major requirements for each of these are summarized in Table 15-7. In addition, the... 

It is not always possible to predict the behaviour of dmgs and formulations in the complicated environments in which they find themselves in vivo, but this should not deter us from at least attempting to rationalise events once they have become known in this way our predictive powers will be honed and will allow us to prevent adverse events in the future. Some unwanted effects are due to the degradation of dmgs and dmg formulations the examination of stability is an important part of assessing the suitability of formulations. This requires a good understanding of the chemistry of the dmg substance and reaction kinetics. This too is the subject of a chapter. 

For a pharmaceutically viable product, approaches to increase protein solubility should render a stable product with excipients suitable for parenteral administration. Identification of a formulation composition optimal for protein solubility and also for protein stability requires an iterative process of evaluating the impact of various parameters on solubility and on stability, independently, and then jointly. 

Phase IV occurs after product approval and launch and the typical stability studies are focused on the marketed product stability program. These studies are conducted to assure that the product continues to meet the stability requirement for the approved expiration date. Therefore, these studies are conducted at the label storage conditions only. However, if new strengths, packages, or formulations are being developed, these studies would be conducted at accelerated storage conditions also. 

The severity of different lubricant applications covers a wide shear stability range. Figure 5.8 shows that engine oils are the mildest application, followed by automatic transmission fluids, hydraulic fluids and rear axle lubricants [63]. Thus, matching shear stability requirements of the application with the selection of VI improver is a key formulation consideration. 

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