Targeting of Inhaled Therapeutics to the Small Airways: Nanoleucine Carrier Formulations

Current dry powder formulations for inhalation deposit a large fraction of their emitted dose in the upper respiratory tract where they contribute to off-target adverse effects and variability in lung delivery. The purpose of the current study is to design a new formulation concept that more effectively targets inhaled dry powders to the large and small airways. The formulations are based on adhesive mixtures of drug nanoparticles and nanoleucine carrier particles prepared by spray drying of a co-suspension of leucine and drug particles from a nonsolvent. The physicochemical and aerosol properties of the resulting formulations are presented. The formulations achieve 93% lung delivery in the Alberta Idealized Throat model that is independent of inspiratory flow rate and relative humidity. Largely eliminating URT deposition with a particle size larger than solution pMDIs is expected to improve delivery to the large and small airways, while minimizing alveolar deposition and particle exhalation.

Targeting of Inhaled Therapeutics to the Small Airways: Nanoleucine Carrier Formulations

Current dry powder formulations for inhalation deposit a large fraction of their emitted dose in the upper respiratory tract where they contribute to off-target adverse effects and variability in lung delivery. The purpose of current study is to design a new formulation concept that more effectively targets inhaled dry powders to the large and small airways. The formulations are based on adhesive mixtures of drug nanoparticles and nanoleucine carrier particles prepared by spray drying of a co-suspension of leucine and drug particles from a nonsolvent. The physicochemical and aerosol properties of the resulting formulations are presented. The formulations achieve 93% lung delivery in the Alberta Idealized Throat model that is independent of inspiratory flow rate and relative humidity. Largely eliminating URT deposition with a particle size larger than solution pMDIs is expected to improve delivery to the large and small airways, while minimizing alveolar deposition and particle exhalation.

Comparison between traditional and nontraditional add-on devices used with pressurised metered-dose inhalers

Add-on devices that are attached to metered-dose inhalers (MDIs) were introduced to improve aerosol delivery. The objective of this study was to determine the efficacy of drug delivery from an MDI when attached to different add-on devices at different inhalation volumes.The total emitted dose (TED) of salbutamol was estimated for the MDI alone and the MDI connected to five different add-on devices (Able valved holding chamber, Tips-haler valved holding chamber, Aerochamber plus flow Vu valved holding chamber, Dolphin chamber, and a handmade water bottle spacer), at inhalation flow of 28.3 L·min−1 with flow volume of 1, 2 and 4 L, assuming young child (aged <6 years), old child (>6 years) and adult inhalation volumes, respectively.The TED% ranged between 84.1% and 87.2% at all inhalation volumes from the MDI alone, which was significantly greater than all MDI add-on device combinations (p<0.05). The TED% delivered to MDI sampling apparatus by a homemade water bottle spacer and Dolphin chamber, as non-antistatic add-on devices, ranged between 30.5% and 35.3%. However, washing these non-antistatic add-on devices with a light detergent before use improved their TED to range between 47.6% and 51.2%. Non-antistatic add-on devices had significantly lower TED (p<0.05) than that delivered by most antistatic add-on devices, which ranged from 51.3% to 71.6%.This study suggests that antistatic add-on devices delivered much more aerosol than non-antistatic add-on devices. However, it may be advised to still use a non-antistatic add-on device, for the sake of solving the coordination problem, and wash it with light detergent before use to improve TED.

Validation of In-vitro Deposition of Emitted Dose Method for Simultaneous Estimation of Formoterol Fumarate and Glycopyrrolate in combined Dry Powder Inhaler Aerosol Pharmaceutical Dosage Form

Formoterol Fumarate and Glycopyrrolate Dry powder inhaler is combined aerosol dosage form. The label claim of this combined dosage form is 25 mcg of Glycopyrrolate and 6 mcg of Formoterol Fumarate per respicap. It is prescribed for treatment of Asthma and COPD. Formoterol Fumarate is anti asthmatic drug (Bronchodilator) and Glycopyrrolate is quaternary ammonium compounds which is Anticholinergic Drug. A bronchodilator is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lungs while Glycopyrrolate blocks muscarinic receptors thus inhibiting cholinergic transmission. Glycopyrrolate is also known as Glycopyrronium Bromide, an Anticholinergic agent. It is used to inhibit salivation and excessive secretions of the respiratory tract preoperatively; reversal of neuromuscular blockade; control of upper airway secretions; and part of treatment for peptic ulcer. The present study aimed to Validate HPLC method for determination of Deposition of emitted dose of Formoterol Fumarate and Glycopyrrolate Analytes. This study covers Precision, Linearity, Accuracy, Robustness, Ruggedness, stability of analytical solution and Specificity. The chromatographic method uses a reversed phase column Purosphere star RP 18e (125 mm × 4.6 mm x 5 μm). The mobile phase was prepared by mixing Buffer : Acetonitrile : Methanol (68 : 24 : 8 %v/v/v) at flow rate 1.0 ml per min with UV and PDA detector 215 nm, column oven adjusted to 25° C with injection volume 100 μL. The method showed a successful application for determination of Formoterol Fumarate and Glycopyrrolate in Dry powder inhaler pharmaceutical formulation.

Generation of High Dose Inhalable Effervescent Dispersions against Pseudomonas aeruginosa Biofilms

Purpose Novel particle engineering approach was used in this study to generate high dose inhalable effervescent particles with synergistic effects against Pseudomonas aeruginosa biofilms. Methods Spray dried co-amorphous salt of ciprofloxacin (CFX) and tartaric acid (TA) was prepared and coated with external layer of sodium bicarbonate and silica coated silver nanobeads. Design of experiments (DOE) was used to optimize physicochemical properties of particles for enhanced lung deposition. Results Generated particles were co-amorphous CFX/TA showing that CFX lost its zwitterionic form and exhibiting distinct properties to CFX/HCl as assessed by FTIR and thermal analysis. Particles exhibited mass mean aerodynamic diameter (MMAD) of 3.3 μm, emitted dose of 78% and fine particle dose of 85%. Particles were further evaluated via antimicrobial assessment of minimum inhibitory concentrations (MIC) and minimum biofilm eradication concentration (MBEC). MIC and MBEC results showed that the hybrid particles were around 3–5 times more effective when compared to CFX signifying that synergistic effect was achieved. Diffusing wave spectroscopy results showed that the silver containing particles had a disruptive effect on rheological properties as opposed to silver free particles. Conclusions Overall, these results showed the potential to use particle engineering to generate particles that are highly disruptive of bacterial biofilms.