Limits...
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.


Differential scanning calorimetry (DSC) curves 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
getmorefigures.php?uid=PMC4608592&req=5

f6-ijn-10-6339: Differential scanning calorimetry (DSC) curves of carvedilol (CAR), Pluronic F127 (PL), sodium deoxycholate (SDC), mannitol (MN), physical mixture (PM), and lyophilized nanosuspension (NS).

Mentions: Samples of individual ingredients, physical mixture, as well as the optimized freeze-dried nanosuspension formula were subjected to solid-state characterization using DSC and PXRD. The DSC curve for the coarse CAR (Figure 6) showed a sharp melting endotherm at 115.47°C indicating the crystalline nature of the drug in accordance with data in the literature.25 Pluronic F127 showed low melting endotherm at 54.86°C.7 SDC demonstrated a broad endotherm probably because of the loss of water molecules followed by an exothermic recrystallization peak at 214°C.53 Mannitol demonstrated a sharp melting endotherm at 167°C, which shows that it is a highly crystalline component. The drug characteristic peak disappeared in the thermogram of freeze-dried nanosuspension and was found with decreased intensity in the thermogram of physical mixture. This might be referred to the dilution effect of the drug with the excipients, especially in the presence of a wide shoulder for SDC that might cover the drug peak. In addition, there is a possibility for decrease or disappearance of drug crystallinity. However, these findings showed that DSC was not a discriminative tool for explaining the changes that occurred in drug crystals during preparation.27


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)

Differential scanning calorimetry (DSC) curves 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

f6-ijn-10-6339: Differential scanning calorimetry (DSC) curves of carvedilol (CAR), Pluronic F127 (PL), sodium deoxycholate (SDC), mannitol (MN), physical mixture (PM), and lyophilized nanosuspension (NS).
Mentions: Samples of individual ingredients, physical mixture, as well as the optimized freeze-dried nanosuspension formula were subjected to solid-state characterization using DSC and PXRD. The DSC curve for the coarse CAR (Figure 6) showed a sharp melting endotherm at 115.47°C indicating the crystalline nature of the drug in accordance with data in the literature.25 Pluronic F127 showed low melting endotherm at 54.86°C.7 SDC demonstrated a broad endotherm probably because of the loss of water molecules followed by an exothermic recrystallization peak at 214°C.53 Mannitol demonstrated a sharp melting endotherm at 167°C, which shows that it is a highly crystalline component. The drug characteristic peak disappeared in the thermogram of freeze-dried nanosuspension and was found with decreased intensity in the thermogram of physical mixture. This might be referred to the dilution effect of the drug with the excipients, especially in the presence of a wide shoulder for SDC that might cover the drug peak. In addition, there is a possibility for decrease or disappearance of drug crystallinity. However, these findings showed that DSC was not a discriminative tool for explaining the changes that occurred in drug crystals during preparation.27

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.