Preparation, optimization, and in vitro simulated inhalation delivery of carvedilol nanoparticles loaded on a coarse carrier intended for pulmonary administration

Aly A Abdelbary,1 Abdulaziz M Al-mahallawi,1 Mohamed E Abdelrahim,2 Ahmed MA Ali3,4 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 2Department of Clinical Pharmacy, 3Department of Pharmaceutics, Faculty of Pharmacy, Beni Suef University,...

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Autores principales:	Abdelbary AA, Al-mahallawi AM, Abdelrahim ME, Ali AMA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a3cd3791aad84bafb62c2ced260d080a
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spelling	oai:doaj.org-article:a3cd3791aad84bafb62c2ced260d080a2021-12-02T02:42:21ZPreparation, optimization, and in vitro simulated inhalation delivery of carvedilol nanoparticles loaded on a coarse carrier intended for pulmonary administration1178-2013https://doaj.org/article/a3cd3791aad84bafb62c2ced260d080a2015-10-01T00:00:00Zhttps://www.dovepress.com/preparation-optimization-and-in-vitro-simulated-inhalation-delivery-of-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Aly A Abdelbary,1 Abdulaziz M Al-mahallawi,1 Mohamed E Abdelrahim,2 Ahmed MA Ali3,4 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 2Department of Clinical Pharmacy, 3Department of Pharmaceutics, Faculty of Pharmacy, Beni Suef University, Beni Suef, Egypt; 4Department of Pharmaceutics, Faculty of Pharmacy, Taif University, Taif, Saudi Arabia Abstract: Carvedilol (CAR) is a potent antihypertensive drug but has poor oral bioavailability (24%). A nanosuspension suitable for pulmonary delivery to enhance bioavailability and bypass first-pass metabolism of CAR could be advantageous. Accordingly, the aim of this work was to prepare CAR nanosuspensions and to use artificial neural networks associated with genetic algorithm to model and optimize the formulations. The optimized nanosuspension was lyophilized to obtain dry powder suitable for inhalation. However, respirable particles must have a diameter of 1–5 µm in order to deposit in the lungs. Hence, mannitol was used during lyophilization for cryoprotection and to act as a coarse carrier for nanoparticles in order to deliver them into their desired destination. The bottom-up technique was adopted for nanosuspension formulation using Pluronic stabilizers (F127, F68, and P123) combined with sodium deoxycholate at 1:1 weight ratio, at three levels with two drug loads and two aqueous to organic phase volume ratios. The drug crystallinity was studied using differential scanning calorimetry and powder X-ray diffractometry. The in vitro emitted doses of CAR were evaluated using a dry powder inhaler sampling apparatus and the aerodynamic characteristics were evaluated using an Andersen MKII cascade impactor. The artificial neural networks results showed that Pluronic F127 was the optimum stabilizer based on the desired particle size, polydispersity index, and zeta potential. Results of differential scanning calorimetry combined with powder X-ray diffractometry showed that CAR crystallinity was observed in the lyophilized nanosuspension. The aerodynamic characteristics of the optimized lyophilized nanosuspension demonstrated significantly higher percentage of total emitted dose (89.70%) and smaller mass median aerodynamic diameter (2.80 µm) compared with coarse drug powder (73.60% and 4.20 µm, respectively). In summary, the above strategy confirmed the applicability of formulating CAR in the form of nanoparticles loaded on a coarse carrier suitable for inhalation delivery. Keywords: aerodynamic diameter, freeze-drying, artificial neural networks, Pluronics, nanosizing, cascade impactorAbdelbary AAAl-mahallawi AMAbdelrahim MEAli AMADove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 6339-6353 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Abdelbary AA Al-mahallawi AM Abdelrahim ME Ali AMA Preparation, optimization, and in vitro simulated inhalation delivery of carvedilol nanoparticles loaded on a coarse carrier intended for pulmonary administration
description	Aly A Abdelbary,1 Abdulaziz M Al-mahallawi,1 Mohamed E Abdelrahim,2 Ahmed MA Ali3,4 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 2Department of Clinical Pharmacy, 3Department of Pharmaceutics, Faculty of Pharmacy, Beni Suef University, Beni Suef, Egypt; 4Department of Pharmaceutics, Faculty of Pharmacy, Taif University, Taif, Saudi Arabia Abstract: Carvedilol (CAR) is a potent antihypertensive drug but has poor oral bioavailability (24%). A nanosuspension suitable for pulmonary delivery to enhance bioavailability and bypass first-pass metabolism of CAR could be advantageous. Accordingly, the aim of this work was to prepare CAR nanosuspensions and to use artificial neural networks associated with genetic algorithm to model and optimize the formulations. The optimized nanosuspension was lyophilized to obtain dry powder suitable for inhalation. However, respirable particles must have a diameter of 1–5 µm in order to deposit in the lungs. Hence, mannitol was used during lyophilization for cryoprotection and to act as a coarse carrier for nanoparticles in order to deliver them into their desired destination. The bottom-up technique was adopted for nanosuspension formulation using Pluronic stabilizers (F127, F68, and P123) combined with sodium deoxycholate at 1:1 weight ratio, at three levels with two drug loads and two aqueous to organic phase volume ratios. The drug crystallinity was studied using differential scanning calorimetry and powder X-ray diffractometry. The in vitro emitted doses of CAR were evaluated using a dry powder inhaler sampling apparatus and the aerodynamic characteristics were evaluated using an Andersen MKII cascade impactor. The artificial neural networks results showed that Pluronic F127 was the optimum stabilizer based on the desired particle size, polydispersity index, and zeta potential. Results of differential scanning calorimetry combined with powder X-ray diffractometry showed that CAR crystallinity was observed in the lyophilized nanosuspension. The aerodynamic characteristics of the optimized lyophilized nanosuspension demonstrated significantly higher percentage of total emitted dose (89.70%) and smaller mass median aerodynamic diameter (2.80 µm) compared with coarse drug powder (73.60% and 4.20 µm, respectively). In summary, the above strategy confirmed the applicability of formulating CAR in the form of nanoparticles loaded on a coarse carrier suitable for inhalation delivery. Keywords: aerodynamic diameter, freeze-drying, artificial neural networks, Pluronics, nanosizing, cascade impactor
format	article
author	Abdelbary AA Al-mahallawi AM Abdelrahim ME Ali AMA
author_facet	Abdelbary AA Al-mahallawi AM Abdelrahim ME Ali AMA
author_sort	Abdelbary AA
title	Preparation, optimization, and in vitro simulated inhalation delivery of carvedilol nanoparticles loaded on a coarse carrier intended for pulmonary administration
title_short	Preparation, optimization, and in vitro simulated inhalation delivery of carvedilol nanoparticles loaded on a coarse carrier intended for pulmonary administration
title_full	Preparation, optimization, and in vitro simulated inhalation delivery of carvedilol nanoparticles loaded on a coarse carrier intended for pulmonary administration
title_fullStr	Preparation, optimization, and in vitro simulated inhalation delivery of carvedilol nanoparticles loaded on a coarse carrier intended for pulmonary administration
title_full_unstemmed	Preparation, optimization, and in vitro simulated inhalation delivery of carvedilol nanoparticles loaded on a coarse carrier intended for pulmonary administration
title_sort	preparation, optimization, and in vitro simulated inhalation delivery of carvedilol nanoparticles loaded on a coarse carrier intended for pulmonary administration
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/a3cd3791aad84bafb62c2ced260d080a
work_keys_str_mv	AT abdelbaryaa preparationoptimizationandinvitrosimulatedinhalationdeliveryofcarvedilolnanoparticlesloadedonacoarsecarrierintendedforpulmonaryadministration AT almahallawiam preparationoptimizationandinvitrosimulatedinhalationdeliveryofcarvedilolnanoparticlesloadedonacoarsecarrierintendedforpulmonaryadministration AT abdelrahimme preparationoptimizationandinvitrosimulatedinhalationdeliveryofcarvedilolnanoparticlesloadedonacoarsecarrierintendedforpulmonaryadministration AT aliama preparationoptimizationandinvitrosimulatedinhalationdeliveryofcarvedilolnanoparticlesloadedonacoarsecarrierintendedforpulmonaryadministration
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Preparation, optimization, and in vitro simulated inhalation delivery of carvedilol nanoparticles loaded on a coarse carrier intended for pulmonary administration

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