Selection of solid dosage form composition through drug–excipient compatibility testing

Abstract

A drug-excipient compatibility screening model was developed by which potential stability problems due to interactions of drug substances with excipients in solid dosage forms can be predicted. The model involved storing drug-excipient blends with 20% added water in closed glass vials at 50 degrees C and analyzing them after 1 and 3 weeks for chemical and physical stability. The total weight of drug-excipient blend in a vial was usually kept at about 200 mg. The amount of drug substance in a blend was determined on the basis of the expected drug-to-excipient ratio in the final formulation. Potential roles of several key factors, such as the chemical nature of the excipient, drug-to-excipient ratio, moisture, microenvironmental pH of the drug-excipient mixture, temperature, and light, on dosage form stability could be identified by using the model. Certain physical changes, such as polymorphic conversion or change from crystalline to amorphous form, that could occur in drug-excipient mixtures were also studied. Selection of dosage form composition by using this model at the outset of a drug development program would lead to reduction of "surprise" problems during long-term stability testing of drug products.

Assessment of Feasibility of Maillard Reaction between Baclofen and Lactose by Liquid Chromatography and Tandem Mass Spectrometry, Application to Pre Formulation Studies

“…Results of the screening test are presented in Table I. As it was expected (7,32), the presence of water promoted the degradation reactions including the Maillard reaction as the brown color develops more significantly in water-containing mixtures (samples 2, 4, 6, and 8).…”

Formulation and in Vitro Evaluation of Once Daily Sustained Release Formulation of Aceclofenac

“…The pellet was placed in the light path and the spectrum obtained. The energy at which any peak in an absorption spectrum appears corresponds to the frequency of a vibration of a part of a sample molecule [14].…”

Physicochemical Properties and Excipient Compatibility Studies of Probiotic Bacillus coagulans Spores

“…Isothermal stress testing involves challenging drugexcipient mixtures in presence of moisture to degradation [20]. Under these conditions B. coagulans spores degraded by approximately 22% in 15 days.…”