Chemical permeation enhancers

Ita, Kevin

doi:10.1016/b978-0-12-822550-9.00005-3

Cited by 5 publications

(1 citation statement)

References 107 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Generally, lipid-based drug delivery, solid dispersion, prodrug, permeation enhancer, micelle formation, particle size reduction, nanoemulsions, complexation, etc. are exploited to improve the diffusion aspects of low permeable class III/IV drugs. − Since the past decade, cocrystallization has been used as an alternative and promising tool to tune diffusion characteristics. Although similar to solubility improvement using cocrystal/salts, modulating diffusion permeability is not straightforward as it is often correlated with heterosynthon, concentration gradient, solubility, crystal density, melting point, and log P (of the coformers).…”

Section: Introductionmentioning

confidence: 99%

Expanding the Crystal Structure Landscape of Pravastatin Complexes: Tuning Solubility, Diffusion, and Pharmacokinetics

Varsa S,

Priya Katukam,

Kole

et al. 2024

Crystal Growth & Design

View full text Add to dashboard Cite

Pravastatin (PRV), a lipid-lowering medication, is prescribed to treat cardiovascular disease and dyslipidemia. Due to its low permeability and high solubility, the biopharmaceutics classification system (BCS) class III drug exhibits poor bioavailability. To overcome the bottlenecks of PRV, novel complexes with Zn and Cu along with a zwitterionic cocrystal with l-proline (PRO) were synthesized. These new solid forms were characterized by SC-XRD, PXRD, DSC, TGA, FT-IR, DVS, and SEM images. Rietveld refinement was used to obtain the 3D coordinates of the PRV–Na–PRO ionic cocrystal hydrate from high-resolution PXRD data. PRV–Cu and Zn complexes were obtained by substituting PRV sodium salt with a Cu/Zn metal. In PRV–Na–PRO cocrystal hydrate, each Na metal is coordinated from carboxylates of PRV (2) and zwitterionic PRO (1) and three water molecules result in an octahedron geometry. Cu is coordinated with two carboxylate anions of PRV (2) and three water molecules, forming a square pyramidal geometry. The PRV–Zn complex maintains an octahedral geometry using four coordination from two carboxylate anions of PRV (2) and two water molecules. The PRV–Na–PRO cocrystal hydrate exhibited higher solubility (1.7-fold) and diffusion profile (1.1-fold) compared to the commercial PRV–Na salt hydrate, whereas PRV–Cu/Zn complexes showed controlled drug release. Surprisingly, the PRV–Na–PRO cocrystal hydrate enhanced peak plasma concentration C max (50 fold) and AUC (14.4 fold) compared to the commercial PRV–Na salt during pharmacokinetics study in rats. The stability of the PRV complexes was supported by ground-state optimization energy calculations. Unlike the moisture-sensitive PRV–Na salt hydrate and PRV–Na–PRO cocrystal hydrate, PRV–Zn/Cu complexes exhibited far superior moisture stability and may offer extended drug release. On the other hand, the PRV–Na–PRO cocrystal hydrate with significantly improved bioavailability can be commercialized following proper formulation that offers moisture stability.

show abstract