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Effect of Carrier Morphology and Surface Characteristics on the Development of Respirable Plga Microcapsules for Sustained-Release Pulmonary Delivery of Insulin Publisher Pubmed



Hamishehkar H1 ; Emami J2 ; Najafabadi AR3 ; Gilani K3 ; Minaiyan M2 ; Mahdavi H4 ; Nokhodchi A5
Authors
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Authors Affiliations
  1. 1. Pharmaceutical Technology Laboratory, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  2. 2. School of Pharmacy and Pharmaceutical Sciences, Isfahan Pharmaceutical Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Aerosol Research Laboratory, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Novel Drug Delivery Systems, Iran Polymer and Petrochemical Institute, Tehran, Iran
  5. 5. Medway School of Pharmacy, The Universities of Kent and Greenwich, Chatham Maritime, ME4 4TB, Kent, Central Ave, United Kingdom

Source: International Journal of Pharmaceutics Published:2010


Abstract

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 μg) 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 μg). 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. © 2010 Elsevier B.V. All rights reserved.
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