Stability solid oral dosage form

KS Murthy, I Ghebre-Sellassie. Current perspectives on the dissolution stability of solid oral dosage forms. J Pharm Sci 82 113-126, 1993. 

A systematic approach should be adopted in the presentation and evaluation of the stability information, incorporating, as appropriate, results from the physical, chemical, biological, and microbiological tests, including particular attributes of the dosage form (e.g., dissolution rate for solid oral dosage forms). 

Iimnediate Release Solid Oral Dosage Forms A significant body of in-fonnation on the stability of the drug product is likely to exist after five years of commercial experience for new molecular entities, or three years of commercial experience for new dosage forms. 

A change in an antioxidant, colorant, stabilizer, or mold releasing agent for production of the container and/or closure to one that is used at similar levels in the packaging of CDER-approved solid oral dosage form products. 

Early on in product development, the potential for the successful development of a solid oral dosage form is assessed, based on the physicochemical properties of the API (1). Prior to solid dosage form development, it is necessary to anticipate the physicochemical properties that can have a major influence on product manufacture and performance. The early development (preformulation and early formulation development) studies should focus on these properties so as to avoid problems at later stages of development. While the molecular properties dictate the intrinsic solubility and the chemical stability of the compound, by controlling the physical form of the compound and by modifying physical properties (e.g., particle size), the dissolution rate can be enhanced with the potential for improving bioavailability. This chapter will focus on physical properties including particle characteristics, and most importantly, the physical form (i.e., solid state) of the API. 

It is commonplace in pharmaceutical formulation to combine two or more polymers within a single dosage form, e.g., gel, semisolid, and solid oral dosage form as, in many instances, this ensures enhanced control of dosage form performance, e.g., stability, drug release rate, spreadability, etc. Once more, both the clinical and nonclinical performance of these systems may be related to their (complex) viscoelastic behavior, and, hence, these systems have been characterized using dynamic oscillatory methods. 

On the other hand, testing at lower humidities would be less challenging for most of the products, in particular for solid oral dosage forms like tablets, which are generally more stable in a dry environment. It is therefore adequate and justified to test the long-term stability of products for countries in Climatic Zone III at higher humidities, e.g., 30°C/65%. 

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