Modeling and Optimization of Terbutaline Emitted from a Dry Powder Inhaler and Influence on Systemic Bioavailability Using Data Mining Technology

Ali, Ahmed Mahmoud Abdelhaleem; Abdelrahim, Mohamed

doi:10.1007/s12247-014-9171-8

Cited by 43 publications

(37 citation statements)

References 33 publications

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“…Trusted models should result in validation correlation R 2 as high as those obtained during model training and testing. The root mean-squared errors (RMSE) were also calculated and compared with those of training and testing (Ali & Abdelrahim, 2014).…”

Section: Modeling and Optimization Of Ofdf Preparationmentioning

confidence: 99%

In vitro/in vivo evaluation of an optimized fast dissolving oral film containing olanzapine co-amorphous dispersion with selected carboxylic acids

et al. 2016

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Improvement of water solubility, dissolution rate, oral bioavailability, and reduction of first pass metabolism of OL (OL), were the aims of this research. Co-amorphization of OL carboxylic acid dispersions at various molar ratios was carried out using rapid solvent evaporation. Characterization of the dispersions was performed using differential scanning calorimetry (DSC), Fourier transform infrared spectrometry (FTIR), X-ray diffractometry (XRD), and scanning electron microscopy (SEM). Dispersions with highest equilibrium solubility were formulated as fast dissolving oral films. Modeling and optimization of film formation were undertaken using artificial neural networks (ANNs). The results indicated co-amorphization of OL-ascorbic acid through H-bonding. The co-amorphous dispersions at 1:2 molar ratio showed more than 600-fold increase in solubility of OL. The model optimized fast dissolving film prepared from the dispersion was physically and chemically stable, demonstrated short disintegration time (8.5 s), fast dissolution (97% in 10 min) and optimum tensile strength (4.9 N/cm 2 ). The results of in vivo data indicated high bioavailability (144 ng h/mL) and maximum plasma concentration (14.2 ng/mL) compared with the marketed references. Therefore, the optimized co-amorphous OL-ascorbic acid fast dissolving film could be a valuable solution for enhancing the physicochemical and pharmacokinetic properties of OL.

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Section: Modeling and Optimization Of Ofdf Preparationmentioning

confidence: 99%

In vitro/in vivo evaluation of an optimized fast dissolving oral film containing olanzapine co-amorphous dispersion with selected carboxylic acids

et al. 2016

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“…setting integer numbers to the crosslinker type). The desired range for each of the output properties was entered into the model optimization step and the desirability function was selected as Btent^in the model optimization window [37]. The specified minimum and maximum values for the output properties were assigned as follows; %EE (68-75 %), PS (150-300 nm), ZP (9.5-15), PDI (0.1-0.3), %Rel-8 h (78-90 %), Q 24 (500-700 μg), lag time (10-20 min), and Kp (0.3-0.6).…”

Section: Modeling and Optimization Of Nanosuspension Formulationmentioning

confidence: 99%

Modeling, Optimization, and In Vitro Corneal Permeation of Chitosan-Lomefloxacin HCl Nanosuspension Intended for Ophthalmic Delivery

et al. 2015

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Lomefloxacin HCl (LF) is a widely used fourthgeneration fluoroquinolone antibiotic. Like most drug solutions administered via ocular route, it is usually eliminated by eye protective mechanisms. Chitosan (CS) is a natural polysaccharide polymer with numerous advantages in ocular delivery with, antibacterial, and antifungal properties. The aims were to formulate and optimize LF nanosuspensions (NS) with enhanced antimicrobial activity and prolonged duration using ionic gelation technique. Formulation variables included drug load, CS concentration, crosslinker type (tripolyphosphate and sodium alginate), and concentration. Nanosuspension properties (particle size, zeta potential, polydispersity index, entrapment efficiency, drug release, and permeation through bovine cornea) were evaluated. The artificial neural networks (ANNs) model showed optimum entrapment efficiency of 70.63 % w/w, particle size of 176±0.28 nm, and zeta potential of 13.65 mV. Transmission electron microscopy illustrated the production of well-defined spherical nanoparticles. The nanosuspensions showed prolonged release of LF for more than 8 h and threefold increase in amount permeated through bovine cornea compared to drug solution. Improved antibacterial activity of the nanosuspension was noted where 2-and 3.5-fold decrease in minimum inhibitory concentration (MIC) of drug against Gram-positive and Gram-negative bacteria were observed, respectively. Twofold decrease in minimum bactericidal concentration (MBC) of drug nanosuspension against both types of bacteria was also demonstrated. Histopathological examination showed compatibility of optimized formulation with eye tissues in rabbit model. Therefore, model-optimized LF nanosuspension could be an ideal solution to ocular infections by virtue of their augmented activity, high compatibility, and improved permeability.

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“…In this formula, the numerator represents the sum of squares for the error term and the denominator represents the total sum of squares. 3 The values of R 2 describe how much of the variance of the dependent variable is accounted for in the model. The ANN structure I(11)-H(2)-O(1) was used for model training (linking input and the output parameters).…”

Section: Modeling Of Nanosuspension Formulaementioning

confidence: 99%

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

Abdelbary¹,

Al-mahallawi²,

Abdelrahim³

et al. 2015

IJN

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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.

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Modeling and Optimization of Terbutaline Emitted from a Dry Powder Inhaler and Influence on Systemic Bioavailability Using Data Mining Technology

Cited by 43 publications

References 33 publications

In vitro/in vivo evaluation of an optimized fast dissolving oral film containing olanzapine co-amorphous dispersion with selected carboxylic acids

In vitro/in vivo evaluation of an optimized fast dissolving oral film containing olanzapine co-amorphous dispersion with selected carboxylic acids

Modeling, Optimization, and In Vitro Corneal Permeation of Chitosan-Lomefloxacin HCl Nanosuspension Intended for Ophthalmic Delivery

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

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