Pharmacokinetics evaluation of soft agglomerates for prompt delivery of enteric pantoprazole-loaded microparticles.
Soft agglomerates containing pantoprazole-loaded microparticles were developed with the aim of prompt delivery of gastro-resistant particles. The objective was to evaluate the relative bioavailability in dogs after the oral administration of soft agglomerates. Gastro-resistant pantoprazole-loaded microparticles prepared by spray drying were mixed with mannitol/lecithin spray-dried powder and agglomerated by vibration. One single oral dose (40mg) was administered to dogs. Each dog received either a reference tablet or hard gelatin capsules containing the agglomerates. The plasma profiles were evaluated by non-compartmental and compartmental approaches, and the pharmacokinetic parameters were determined. The agglomerates presented 100% of drug particle loading and a production yield of 80.5%. The amount of drug absorbed after oral dosing was similar after reference or agglomerate administration, leading to a relative bioavailability of 108%. The absorption lag-time was significantly reduced after agglomerate administration (from 135.5+/-50.6 to 15.0+/-2.5min). The agglomerated gastro-resistant pantoprazole-loaded microparticles reduced time to peak plasma. The agglomerates were equivalent to the reference tablets in terms of extent but not in terms of rate of absorption, showing that this formulation is an alternative to single-unit oral dosing with enteric coating and with the advantage of reducing time to effect.
Raffin
Renata P
RP
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Colomé
Letícia M
LM
Hoffmeister
Cristiane R D
CR
Colombo
Paolo
P
Rossi
Alessandra
A
Sonvico
Fabio
F
Colomé
Lucas M
LM
Natalini
Claudio C
CC
Pohlmann
Adriana R
AR
Costa
Teresa Dalla
TD
Guterres
Silvia S
SS
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D004285:Dogs; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D004339:Drug Compounding / Q000379:methods*; D007408:Intestinal Absorption; D008863:Microspheres; D000077402:Pantoprazole; D010316:Particle Size
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D004337:Drug Carriers; D000077402:Pantoprazole