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

Abdelbary AA, Al-mahallawi AM, Abdelrahim ME, Ali AM - Int J Nanomedicine (2015)

Bottom Line: The artificial neural networks results showed that Pluronic F127 was the optimum stabilizer based on the desired particle size, polydispersity index, and zeta potential.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

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.

No MeSH data available.


Powder X-ray diffraction patterns of carvedilol (CAR), Pluronic F127 (PL), sodium deoxycholate (SDC), mannitol (MN), physical mixture (PM), and lyophilized nanosuspension (NS).
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f7-ijn-10-6339: Powder X-ray diffraction patterns of carvedilol (CAR), Pluronic F127 (PL), sodium deoxycholate (SDC), mannitol (MN), physical mixture (PM), and lyophilized nanosuspension (NS).

Mentions: The PXRD patterns shown in Figure 7 indicated that CAR exhibited three sharp characteristic diffraction lines at 2θ of 5.8°, 14.7°, and 24.5° and multiple short lines between 2θ of 10° and 30°. Pluronic F127 demonstrated two reflections at 2θ of 19° and 23°. SDC showed a characteristic halo for an amorphous structure, while mannitol showed a crystalline diffraction pattern with characteristic lines of increasing height at 2θ of 5°, 10°, 14°, 18°, and 22°. The physical mixture showed a summation of diffraction lines mostly typical to parent crystalline components. The freeze-dried nanosuspension demonstrated two sharp diffraction lines between 2θ of 9.6° and 20.2° with two short lines in between 2θ of 14° and 18°. This pattern is mostly similar to the characteristic diffraction lines observed for crystalline CAR. However, the diffraction lines were shifted to higher 2θ values possibly because of a new polymorphic form (IV), which was reported in the literature to be formed during antisolvent precipitation of crystalline CAR.54 The new sharp diffraction line observed in the nanosuspension pattern at 72° appeared to belong to SDC. This reflection line may confirm that SDC molecules had undergone crystallization during the freeze-drying process. In summary, the aforementioned results showed that CAR crystalline structure was evident. Similar results of obtaining crystalline nanosuspension were observed by Raju et al working on nevirapine.55


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

Abdelbary AA, Al-mahallawi AM, Abdelrahim ME, Ali AM - Int J Nanomedicine (2015)

Powder X-ray diffraction patterns of carvedilol (CAR), Pluronic F127 (PL), sodium deoxycholate (SDC), mannitol (MN), physical mixture (PM), and lyophilized nanosuspension (NS).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608592&req=5

f7-ijn-10-6339: Powder X-ray diffraction patterns of carvedilol (CAR), Pluronic F127 (PL), sodium deoxycholate (SDC), mannitol (MN), physical mixture (PM), and lyophilized nanosuspension (NS).
Mentions: The PXRD patterns shown in Figure 7 indicated that CAR exhibited three sharp characteristic diffraction lines at 2θ of 5.8°, 14.7°, and 24.5° and multiple short lines between 2θ of 10° and 30°. Pluronic F127 demonstrated two reflections at 2θ of 19° and 23°. SDC showed a characteristic halo for an amorphous structure, while mannitol showed a crystalline diffraction pattern with characteristic lines of increasing height at 2θ of 5°, 10°, 14°, 18°, and 22°. The physical mixture showed a summation of diffraction lines mostly typical to parent crystalline components. The freeze-dried nanosuspension demonstrated two sharp diffraction lines between 2θ of 9.6° and 20.2° with two short lines in between 2θ of 14° and 18°. This pattern is mostly similar to the characteristic diffraction lines observed for crystalline CAR. However, the diffraction lines were shifted to higher 2θ values possibly because of a new polymorphic form (IV), which was reported in the literature to be formed during antisolvent precipitation of crystalline CAR.54 The new sharp diffraction line observed in the nanosuspension pattern at 72° appeared to belong to SDC. This reflection line may confirm that SDC molecules had undergone crystallization during the freeze-drying process. In summary, the aforementioned results showed that CAR crystalline structure was evident. Similar results of obtaining crystalline nanosuspension were observed by Raju et al working on nevirapine.55

Bottom Line: The artificial neural networks results showed that Pluronic F127 was the optimum stabilizer based on the desired particle size, polydispersity index, and zeta potential.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

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.

No MeSH data available.