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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

Effect of carrier morphology and surface characteristics on the development of respirable PLGA microcapsules for sustained-release pulmonary delivery of insulin

Hamishehkar, Hamed, Emami, Jaber, Najafabadi, Abdolhossien Rouholamini, Gilani, Kambiz, Minaiyan, Mohsen, Mahdavi, Hamid and Nokhodchi, Ali (2010) Effect of carrier morphology and surface characteristics on the development of respirable PLGA microcapsules for sustained-release pulmonary delivery of insulin. International Journal of Pharmaceutics, 389 (1-2). pp. 74-85. ISSN 0378-5173 (doi:https://doi.org/10.1016/j.ijpharm.2010.01.021)

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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±3.74g) 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±2.51g). 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.

Item Type: Article
Additional Information: Available online 18 January 2010.
Uncontrolled Keywords: dry powder inhalation, carrier, mannitol, sorbitol, insulin, particle engineering, PLGA
Subjects: R Medicine > RS Pharmacy and materia medica
Pre-2014 Departments: School of Science
School of Science > Department of Medway Sciences
Related URLs:
Last Modified: 14 Oct 2016 09:09
Selected for GREAT 2016: None
Selected for GREAT 2017: None
Selected for GREAT 2018: None
Selected for GREAT 2019: None
URI: http://gala.gre.ac.uk/id/eprint/3512

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