Preparation and in vitro/in vivo evaluation of revaprazan hydrochloride nanosuspension

• Published in: International journal of pharmaceutics Vol. 408; no. 1-2; pp. 157 - 162
• Main Authors: Li, Wei, Yang, Yonggang, Tian, Yongshou, Xu, Xinlan, Chen, Yang, Mu, Liwei, Zhang, Yaqiong, Fang, Liang
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15-04-2011; Elsevier
• Subjects: Administration, Oral; Animals; Bioavailability rats; Biological and medical sciences; Biological Availability; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Crystallization; Dissolution; Dose-Response Relationship, Drug; Drug Carriers - chemistry; Freeze Drying; General pharmacology; High pressure homogenization; Male; Medical sciences; Microscopy, Electron, Scanning; Molecular Structure; Nanoparticles - chemistry; Nanosuspension; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phase Transition; Powders; Proton Pump Inhibitors - administration & dosage; Proton Pump Inhibitors - chemistry; Proton Pump Inhibitors - pharmacokinetics; Pyrimidinones - administration & dosage; Pyrimidinones - chemistry; Pyrimidinones - pharmacokinetics; Rats; Rats, Wistar; Revaprazan hydrochloride; Solubility; Surface Properties; Tetrahydroisoquinolines - administration & dosage; Tetrahydroisoquinolines - chemistry; Tetrahydroisoquinolines - pharmacokinetics; X-Ray Diffraction; High pressure homogenization; Bioavailability rats; Nanosuspension; Dissolution; Revaprazan hydrochloride; Evaluation; Pharmaceutical technology; Rat; Revaprazan; Rodentia; Homogenization; Bioavailability; In vitro; Proton pump inhibitor; High pressure; In vivo; Vertebrata; Mammalia; Animal; Preparation; Pharmacokinetics; Nanotechnology
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2011.01.059

Revaprazan hydrochloride (RH) is a new reversible proton pump inhibitor. However, due to poor water solubility, oral bioavailability of the drug was relatively low. To investigate the particle size reduction effect of RH on dissolution and absorption, three suspensions that containing different sized particles were prepared by high pressure homogenization and in vitro/in vivo evaluations were carried out. DSC and powder X-ray diffraction were used to study crystalline state of freeze dried powder of RH suspensions and the results showed that particles of RH microsuspension and nanosuspension remained in the same crystalline state as coarse suspension, but had lower lattice energy. In the in vitro dissolution test, both microsuspension and nanosuspension showed increased dissolution rate. In the in vivo evaluation, compared to coarse suspension, RH nanosuspension exhibited significant increase in AUC0–t, Cmax and decrease in Tmax, MRT. Nevertheless, RH microsuspension did not display any significant differences in these pharmacokinetic parameters compared to the coarse suspension. The findings revealed that particle size reduction can influence RH absorption in gastrointestinal tract and nanosuspension can enhance oral bioavailability of RH in rats.