Effect of carrier morphology and surface characteristics on the development of respirable PLGA microcapsules for sustained-release pulmonary delivery of insulin.
The effect of morphology and surface characteristics of carriers were investigated for development of dry powder inhaler (DPI) formulation of insulin-loaded poly (D,L-lactic-co-glycolic acid) microcapsules for sustained-release pulmonary delivery of insulin. Microcapsule/carrier powder mixtures were prepared consisting of insulin-loaded PLGA microcapsules and sorbitol or mannitol as the carriers with various particle surface morphologies prepared by spray-drying and freeze-drying techniques. Powders were assessed by particle size analyzer, scanning electron microscopy, surface area analyzer, atomic force microscopy, helium pycnometer, X-ray diffraction, differential scanning calorimetery, bulk and tapped densitometers. Aerosol dispersion of microcapsules was examined by a twin impinger using Spinhaler device. The flowability results showed that the lowest (27.51+/-2.24%) and the highest (48.53+/-3.36%) Carr's indices were obtained for the samples containing sieved mannitol and spray-dried mannitol, respectively. The in vitro inhalation properties of the powder mixture prepared using various carrier shape and surface morphology were different, suggesting that the separation of microcapsules from carrier was a determining step to improve inhalation properties of DPIs. The results showed that the highest fine particle fraction (18.3+/-1.65%) and fine particle dose (62.22+/-3.74 microg) were obtained for the microcapsules formulated with sieved mannitol and these values were the lowest when the sieved mannitol was replaced by sieved sorbitol (10.5+/-0.86% and 35.70+/-2.51 microg). It was concluded that optimization of surface roughness is a critical parameter in development of DPIs. It also suggested that the elongation of carrier particles may play an important role in determining the aerosolization properties of the microcapsules. It seems that decrease in crystalline content of carriers may contribute to a decreased in fine particle fraction delivered.
Hamishehkar
Hamed
H
Pharmaceutical Technology Laboratory, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Emami
Jaber
J
Najafabadi
Abdolhossien Rouholamini
AR
Gilani
Kambiz
K
Minaiyan
Mohsen
M
Mahdavi
Hamid
H
Nokhodchi
Ali
A
D000280:Administration, Inhalation; D000336:Aerosols; D002214:Capsules; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D005612:Freeze Drying; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D008353:Mannitol / Q000737:chemistry; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013012:Sorbitol / Q000737:chemistry
D000336:Aerosols; D002214:Capsules; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D007328:Insulin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D008353:Mannitol; D013012:Sorbitol