Evaluation of cilnidipine-loaded self-micro-emulsifying drug delivery system (SMEDDS) by quantification of comparative pharmacokinetic parameters using validated LC-ESI-MS/MS bioanalytical method and pharmacodynamic assessment.
Ann Pharm Fr
; 82(6): 1134-1149, 2024 Nov.
Article
en En
| MEDLINE
| ID: mdl-39089366
ABSTRACT
OBJECTIVE:
Regardless of having desired therapeutic properties many of the recently approved drugs are removed from the developmental pipeline for their clinical use due to low solubility and permeability. Conventional dosage forms are found relatively unsuitable for achieving desired pharmacokinetic and pharmacodynamics profiles. Cilnidipine is 1,4 dihydropyridine derivative calcium channel blocker used for the treatment of hypertension.METHOD:
The aim and objective of this study was to develop a precise and significant method in LC-MS/MS for quantification of pharmacokinetic parameters of a cilnidipine-loaded self-micro-emulsifying drug delivery system in rat plasma and simultaneously assessed pharmacodynamic characters in comparison with the marketed cilnidipine tablet. Another potential aim of this study is to reduce the dose of the drug in order to counter the dose-dependent toxicities related to chronic use. In the present study, the parent and product ion of cilnidipine was m/z 491.3\237.1.RESULT:
The plasma was extracted by protein precipitation technique. The calibration standard concentrations were 1.875, 3.75, 7.50, 15.00, 30.00, 60.00ng/mL and LLOQ, low-quality control, middle-quality control and high-quality control were 1.87, 5.62, 22.50, 45.00ng/mL, respectively. The mobile phase composition was 0.1% formic acid in Milli Q water with 10mM Ammonium acetate as an aqueous solvent and 0.1% formic acid in methanol as an organic solvent. Following oral administration of optimized formulation Cmax (peak plasma concentration) was achieved 21.02±3.17ng/mL at 0.866±0.11h (Tmax), whereas in the case of marketed tablet Cmax (peak plasma concentration) was achieved 10.16±0.89ng/mL at 0.93±0.11h (Tmax).DISCUSSION:
The in-vivo characterizations of the optimized SMEDDS showed significantly better pharmacokinetic parameters in Wistar rats and showed almost 2.4 times enhanced relative bioavailability as compared to the marketed tablet of cilnidipine which was observed to be correlating to our findings with noninvasive blood pressure parameter of Wistar rats.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dihidropiridinas
/
Bloqueadores de los Canales de Calcio
/
Sistemas de Liberación de Medicamentos
/
Emulsiones
/
Espectrometría de Masas en Tándem
Límite:
Animals
Idioma:
En
Revista:
Ann Pharm Fr
Año:
2024
Tipo del documento:
Article
País de afiliación:
India
Pais de publicación:
Francia