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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.


Percentage of CAR dissolved from optimized nanosuspension formula compared to the coarse drug.Abbreviation: CAR, carvedilol.
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f8-ijn-10-6339: Percentage of CAR dissolved from optimized nanosuspension formula compared to the coarse drug.Abbreviation: CAR, carvedilol.

Mentions: The lyophilized nanosuspension formula showed a significant increase in the rate and extent of dissolution and the dissolution rate was maintained at higher level throughout all time intervals compared with the coarse CAR powder (Figure 8). Within 10 minutes, almost 76.63% of CAR was dissolved from the nanosuspension formula compared with only 24.11% for the coarse CAR powder, respectively. After 60 minutes, the dissolution was complete (≈100.00%) for the nanosuspension formula compared with only 44.82% for the coarse CAR powder, respectively. MDT was equal to 8.94 minutes in the case of coarse drug powder. The optimized nanosuspension formula showed a significant decrease in MDT to be 5.26 minutes (P<0.05). The f2 was calculated to compare the dissolution profiles of the coarse drug powder and the optimized nanosuspension formula and was found to be 14.24. Being lower than 50, this indicates the presence of significant difference in the release profiles.38


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)

Percentage of CAR dissolved from optimized nanosuspension formula compared to the coarse drug.Abbreviation: CAR, carvedilol.
© Copyright Policy
Related In: Results  -  Collection

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

f8-ijn-10-6339: Percentage of CAR dissolved from optimized nanosuspension formula compared to the coarse drug.Abbreviation: CAR, carvedilol.
Mentions: The lyophilized nanosuspension formula showed a significant increase in the rate and extent of dissolution and the dissolution rate was maintained at higher level throughout all time intervals compared with the coarse CAR powder (Figure 8). Within 10 minutes, almost 76.63% of CAR was dissolved from the nanosuspension formula compared with only 24.11% for the coarse CAR powder, respectively. After 60 minutes, the dissolution was complete (≈100.00%) for the nanosuspension formula compared with only 44.82% for the coarse CAR powder, respectively. MDT was equal to 8.94 minutes in the case of coarse drug powder. The optimized nanosuspension formula showed a significant decrease in MDT to be 5.26 minutes (P<0.05). The f2 was calculated to compare the dissolution profiles of the coarse drug powder and the optimized nanosuspension formula and was found to be 14.24. Being lower than 50, this indicates the presence of significant difference in the release profiles.38

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.