Stability physicochemical

DF Driscoll, MN Bacon, BR Bistrian. Physicochemical stability of two types of intravenous lipid emulsion as total nutrient admixtures. J Parent Enteral Nutr 24(1) 15-22, 2000. 

In addition to the additives used in a formulation to help stabilize the protein to freezing, the residual moisture content of the lyophilized powder needs to be considered. Not only is moisture capable of affecting the physicochemical stability of the protein itself, equally important is the ability of moisture to affect the Tg of the formulation. Water acts as a plasticizer and depresses the Tg of amorphous solids [124,137,138]. During primary drying, as water is gradually removed from the product, the Tg increases accordingly. The duration and temperature of the secondary drying step of the lyophilization process determines how much moisture remains bound to the powder. Usually lower residual moisture in the finished biopharmaceutical product leads to enhanced stability. Typically, moisture content in lyophilized formulations should not exceed 2% [139]. The optimal moisture level for maximum stability of a particular product must be demonstrated on a case-by-case basis. 

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. 

In addition to considering an adjusted buffering range in mixed solvent systems, the effects of dilution on the pH of the formulation should also be considered (Rubino, 1987). As formulations containing mixed solvent systems are diluted, the solvent effects onWIievjil decrease. For example, the a of the buffer acid will decrease as the formulation is diluted due to the dilution of the cosolvent. The consequences of the pqbWnges on the physicochemical stability of the active compounds should be carefully studied. 

Can API be Micronized The particle size of drug substance at the micron level is critical to achieving blending uniformity and uniformity of dosage unit.16,17 If the drug substance cannot be micronized due to physicochemical stability or material properties, consider dissolving the dmg in solution for forwarding processes. 

Unsatisfactory physicochemical stability of the sorbent. Titanium hydroxide is slightly soluble in seawater (0.1 mg/1 [165]) and also shows some degradation upon aging. Mixed titanium and zirconium oxide-type sorbents, known as thermoxides with much better stability [178, 179] were developed. 

Moisture retained within the stopper could effuse out and enter the lyophilized plug, thus increasing its residual moisture over time. It is reasonable to suppose that the temperature of storage might influence the rate of effusion. As mentioned in Section 3.3, elevated temperatures are often used to screen formulations and predict their shelf lives based on potency and other physicochemical stability parameters. It is therefore important to know whether the residual moisture of the lyophilized product stored at higher temperatures is comparable to that for the same product under the regular storage conditions. 

Hasegawa, K. Hashi, K. Okada, R. Physicochemical stability of pharmaceutical phosphate buffer solutions. I. com-plexation behavior of Ca(II) with additives in phosphate buffer solutions. J. Parenter. Sci. Technol. 1982,36,128-133. 

Aqueous solubility is one of the most important physicochemical properties. It is believed that a drug has to be in solution to be absorbed.35 From the pharmaceutical development point of view, the solid state form is another important factor that affects solubility, the dissolution rate, and eventually developability. The solid state form is the determinant of, to some extent, physicochemical stability, intellectual property, and formulation scalability this factor should be carefully examined and optimized. Change in crystallinerity from different chemical processes, in some cases, results in a big difference in bioavailability when the drug is delivered by a solid dosage formulation. 

In the solid state, the form of the drug will affect both its solubility and its physicochemical stability. A full characterization of the drug in the solid state will often include a determination of the melting point and heat of fusion using differential... 

Properties Chemical structure solubility in water, other solvents such as ether, ethanol, acetone and buffers of different pH its isomeric nature including stereochemical configuration partition coefficient and the existence of polymorphs copies of infrared, nuclear magnetic resonance (proton and C-13), ultraviolet and mass spectra information on the chemical and physicochemical stability if relevant (e.g. formation of a hydrate, change of polymorphic form) ... 

The enhanced physical properties for supercritically produced salme-terol (e.g., high crystallinity, polymorphic purity, powder uniformity) correlate well with the enhanced dispersion and flow behavior of this powder. However, as shown in some other investigations (12,28), particle size and shape, surface energy, and crystallinity may have to be optimized separately, using all process parameters available, perhaps including a coformulation step. For some compounds with low solubility in water, a compromise must be found between improved bioavailability and physicochemical stability. 

Naini, V., P. R. Byron, and E. M. Philips. 1998. Physicochemical stability of crystalline sugars and their spray-dried forms Dependence upon relative humidity and suitability for use in powder inhalers. Drug Dev. Ind. Pharm. 24 (10) 895-909. 

The immobilization system should be described in detail. Tests to indicate the physicochemical stability of both the system and its carrier and enzyme are essential. 

For a biocompatible formulation suitable for human administration, triglycerides and monoglycerides have been chosen as the biomaterials for LS because of their high biocompatibility, high physicochemical stability, and drug delivery release. LS were prepared by two alternative approaches, namely, the melt dispersion and the solvent evaporation techniques (Figure 2.1 and Table 2.1). 

F. Nakamura, M. Fujitani, Y. Machida, and T. Nagai, Physicochemical stability of halopredone acetate ground mixtures with biocompatible polymers [in Japanese], Yakuzaigaku 53, 161-168(1993). 

Y. Matsuda, M. Totsuka, M. Onoe, and E. Tatsumi, Amorphism and physicochemical stability of spray-dried frusemide, J. Pharm. Pharmacol. 44, 627-633(1992). 

T. Yamaguchi, M. Nishimura, R. Okamoto, T. Takeuchi, and K. Yamamoto, Glass formation of 4"-0-(4-methoxyphenyl)acetyltylosin and physicochemical stability of the amorphous solid, Int. J. Pharm. 85, 87-96 (1992). 

M. Totsuka, R. Teraoka, and Y. Matsuda, Physicochemical stability of nitrofurantoin anhydrate and monohydrate under various temperature and humidity conditions, Pharm. Res. 8, 1066-1068 (1991). 

The physicochemical stability of the compound may raise issues during preformulation. Some hydrated compounds may convert to an amorphous form upon dehydration and some may become chemically labile. This is true of cephradine dihydrate that dehydrates to become amorphous and undergoes subsequent oxidation. Other compounds may convert from a lower to a higher state of hydration yielding... 

Organic acids make major contributions to the composition, stability and organoleptic qualities of wines, especially white wines (Ribereau-Gayon etal., 1982) (Jackson, 1994). Their preservative properties also enhance wines microbiological and physicochemical stability. 

On the other hand, it is a good thing that wines have such low pH values, as this enhances their microbiological and physicochemical stability. Low pH hinders the development of microorganisms, while increasing the antiseptic fraction of snlfnr dioxide. The influence of pH on physicochemical stability is due to its effect on the soln-bility of tartrates, in particular potassium bitartrate but, above all, calcium tartrate and the donble salt calcinm tartromalate. 

---