Xilobam: Effect of salt form on pharmaceutical properties

Abstract

In an e f f o r t t o p r o t e c t xilobam from t h e e f f e c t s of h i g h temperatures and h i g h h u m i d i t i e s w i t h o u t a d v e r s e l y a f f e c t i n g i t s d i s s o l u t i o n from t a b l e t s , t h r e e a r y l s u l f o n i c a c i d s a l t s and t h e s a c c h a r i n s a l t were p r e p a r e d . A l l o f t h e s a l t s were determined t o be more s t a b l e a t 74% r e l a t i v e humidity and 70' t h a n t h e f r e e b a s e .I n s p i t e of t h e l a r g e d i f f e r e n c e s between t h e e f f e c t of h i g h humidity a t a h i g h temperature on t h e s a l t s v e r s u s t h e f r e e b a s e , t h e

Salts of Therapeutic Agents: Chemical, Physicochemical, and Biological Considerations

“…In fact, it has been found that the presence of aryl groups in the sulfate counterion for this drug protected the base from getting easily hydrolyzed in the presence of high humidity and high temperatures. The formation of hydrophobic salts allows pharmaceutical companies to prepare more stable drugs without affecting their bioavailability [ 16 ]. Salt formation leads to increased lipophilicity as a result of the neutralization of the overall electrostatic charge, thereby enhancing the membrane permeability of hydrophilic molecules.…”

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).…”

Integration of active pharmaceutical ingredient solid form selection and particle engineering into drug product design

“…Chemical degradation of API commonly defines the shelf life of a drug product. It has been shown that different polymorphs or salts of an API have different chemical stability [77,78]. The crystal structure of the API may be important in chemical stability.…”

“…It has been shown that different polymorphs or salts of an API have different chemical stability. [77,78] The crystal structure of the API may be important in chemical stability. On rare occasions, the structure of the API may leave it prone to degradation through the location of the reactive groups in the crystal structure; this is referred to as topochemistry.…”