Stability solid dosage forms

Fractional Order. In the decomposition of pure solids, the kinetics of reactions can often be more complex than simple zero- or first-order processes. Carstensen [88] has reviewed the stability of solids and solid dosage forms as well as the equations that can be used in these cases. In addition to zero- and first-order kinetics, solid-state degradations are often described by fractional-order equations. 

Colorants do not contribute to therapeutic activity, nor do they improve product bioavailability or stability. Indeed, they increase the cost and complication of the manufacturing process. Their main role is to facilitate identification and to enhance the esthetic appearance of the product. In common with all material to be ingested by humans, solid dosage forms are severely restricted in the coloring agents that are allowable. This situation is complicated by the lack in international agreement on an approved list of colorants suitable for ingestion. 

Primary container-closure system-related data will need to cover storage, transportation, and use. The choice of materials of construction, their description, and the ability of the container-closure system to protect from moisture and/or light will need to be considered. The compatibility of the container-closure and its contents will need to consider sorption, leaching, and safety. The performance of the container-closure system will also need to be considered in terms of dose delivery from any associated device that is to be supplied as part of the product. Container-closure components will require adequate specifications covering description, identification, critical dimensional tolerances, and test methodology (including pharma-copeial and noncompendial methods). More data are likely to be required for liquid or semi-liquid products than for solid dosage forms. In the latter, product stability data and container-closure system specifications may suffice. 

Although most often connected with investigations of solid dosage forms, diffuse reflectance spectroscopy can also be used to characterize alternative formulations. Through the use of a special sample cell, the technique has been used to study the stability of emulsions [37]. In this work, it was found that information could be obtained that pointed toward subtle changes in the emulsion microenvironment. 

Badawy, S.I., Williams, R.C., and Gilbert, D.L., Chemical stability of an ester prodrug of a glycoprotein Ilb/IIIa receptor antagonist in solid dosage forms,. Pharm. Sci., 88, 428,1999. 

Formulation and stability difficulties occur less frequently with solid dosage forms than with liquid pharmaceutical preparations. For this reason, most new drugs are marketed as... 

Nakabayashi, K., Shimamoto,T., and Mima, H. (1980), Stability of packaged solid dosage forms. I. shelf-life prediction for packaged tablets liable to moisutre damage, Pharm. Chem. Bull., 28,1090-1098. 

Murthy, K. S., and Ghebere-Sellassie, I. Current perspectives on the dissolution stability of solid dosage forms. J. Pharm. Sci. 82 113-26, 1993. 

APV (1981) International Association for Pharmaceutical Technology Praxis der Validierung (Validation in Practice), Symposium (1981-1982, Gelsenkirchen) [6] Terminology, sterile, semisolid, and solid dosage forms in development and production, analytical methods and stability evaluation, packaging development and packaging validation transfer, cost-effectiveness... 

Nyqvist H, Wadsten T. Preformulation of solid dosage forms light stability testing of polymorphs as a part of a preformulation process. Acta Pharm Technol 1986 32 130-132. 

Carstensen JT. Stability of solids and solid dosage forms. J Pharm Sci 1974 63 1-14. 

There are a number of crystal aspects of the API that should be briefly examined. Knowledge of crystal habit, particle size distribution, surface area, and optical properties are important because these characteristics will affect the stability of all solid dosage forms in excipient compatibility testing (9,10). Although single crystal data may not be available at early formulation stages, predicted data may be available, based on powder x-ray diffraction (PXRD) studies, and should be considered (11). 

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). 

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