L-649,923 — The selection of an appropriate salt form and preparation of a stable oral formulation

Phase Transformation in Thiamine Hydrochloride Tablets: Influence on Tablet Microstructure, Physical Properties, and Performance

“…For example, the solubility enhancement provided by an amorphous form has the potential to enhance bioavailability 2. A metastable form may progress through pharmaceutical development because of the inability to crystallize the stable form 3. Finally, a metastable form may be used unintentionally, which may become evident from the appearance of the previously unknown stable form during later stages of development 4.…”

Ionization States in the Microenvironment of Solid Dosage Forms: Effect of Formulation Variables and Processing

“…The immediate environment of the drug in a formulation can influence salt to free acid/base conversions thereby causing instability or affecting product performance (14,15). Often, the free acid/base forms of drugs are inherently unstable and hence salt forms have to be used in formulations (1,16). Minimizing exposure to water during processing and the use of an alkalinizer minimized the conversion of a stable salt to an unstable free acid, thereby improving stability during the process and storage (1).…”

Solid-State Surface Acidity and pH-Stability Profiles of Amorphous Quinapril Hydrochloride and Silicate Formulations

“…Authors have reported the use of acidic or basic components (i.e., pH‐modifiers) in the formulation to control surface acidity of the formulation at an optimum pH and improve drug stability 2, 21–26. Badawy et al22, 23 used acids in solid formulations, added as dry blends or as solutions during wet granulation, to reduce the hydrolysis of ester prodrugs.…”

“…The stabilization was attributed to a decrease in microenvironmental pH of the formulation, which was approximated by the pH of saturated solutions of the acids. Other studies reported that the addition of sodium carbonate as a basic pH‐modifier into solid formulations (using dry blending or wet granulation process) reduced acid‐catalyzed degradation of drugs, presumably due to increased microenvironmental pH of the formulation 21, 25. Hailu and Bogner26 investigated the ability of acidic and basic pH‐modifiers to improve the chemical stability of amorphous quinapril hydrochloride (QHCl) prepared by cryo‐grinding with different pH grades of silicates.…”