Engineered Carrier with a Long Time of Flight (TOF) to Improve Drug Delivery From Dry Powder Inhalation Aerosols

A lactose carrier with long TOF was engineered to improve drug deposition from DPIs. The particles were engineered by contacting spray-dried particles with a solvent in which these have a poor solubility. The process increased the particles hollow volume without affecting their original shape. The long TOF was demonstrated by carrier deposition in the lower stage of the TSI, which was up to 9 -fold higher compared to the conventional lactose. The highest deposition of the long TOF carrier was obtained at the lowest inhalation flow rate (24 L/min). The % Fine Particle Fraction of salbutamol sulphate was up to 50% when long TOF carrier was used. Importantly, this study has shown that adhesion drug/carrier has no negative effect on drug deposition, when a long TOF carrier is used

Evidence for the existence of powder sub-populations in micronized materials : Aerodynamic size-fractions of aerosolized powders possess distinct physicochemical properties

This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Purpose: To investigate the agglomeration behaviour of the fine ( 12.8 µm) particle fractions of salmeterol xinafoate (SX) and fluticasone propionate (FP) by isolating aerodynamic size fractions and characterising their physicochemical and re-dispersal properties. Methods: Aerodynamic fractionation was conducted using the Next Generation Impactor (NGI). Re-crystallized control particles, unfractionated and fractionated materials were characterized for particle size, morphology, crystallinity and surface energy. Re-dispersal of the particles was assessed using dry dispersion laser diffraction and NGI analysis. Results: Aerosolized SX and FP particles deposited in the NGI as agglomerates of consistent particle/agglomerate morphology. SX particles depositing on Stages 3 and 5 had higher total surface energy than unfractionated SX, with Stage 5 particles showing the greatest surface energy heterogeneity. FP fractions had comparable surface energy distributions and bulk crystallinity but differences in surface chemistry. SX fractions demonstrated higher bulk disorder than unfractionated and re-crystallized particles. Upon aerosolization, the fractions differed in their intrinsic emission and dispersion into a fine particle fraction (< 5.0 µm). Conclusions: Micronized powders consisted of sub-populations of particles displaying distinct physicochemical and powder dispersal properties compared to the unfractionated bulk material. This may have implications for the efficiency of inhaled drug deliveryPeer reviewe

Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez Breezhaler® 150 and 300 μg

Onbrez Breezhaler® is a low-resistance capsule-based device that was developed to deliver indacaterol maleate. The study was designed to investigate the effects of both maximum flow rate (MIF) and inhalation volume (Vin) on the dose emission of indacaterol 150 and 300 μg dose strengths after one and two inhalations using dose unit sampling apparatus (DUSA) as well as to study the aerodynamic characteristics of indacaterol Breezhaler® using the Andersen cascade impactor (ACI) at a different set of MIF and Vin. Indacaterol 150 and 300 μg contain equal amounts of lactose per carrier. However, 150 μg has the smallest carrier size. The particle size distribution (PSD) of indacaterol DPI formulations 150 and 300 μg showed that the density of fine particles increased with the increase of the primary pressure. For both strengths (150 μg and 300 μg), ED1 increased and ED2 decreased when the inhalation flow rate and inhaled volume increased. The reduction in ED1 and subsequent increase in ED2 was such that when the Vin is greater than 1 L, then 60 L/min could be regarded as the minimum MIF. The Breezhaler was effective in producing respirable particles with an MMAD ≤5 μm irrespective of the inhalation flow rate, but the mass fraction of particles with an aerodynamic diameter <3 μm is more pronounced between 60 and 90 L/min. The dose emission of indacaterol was comparable for both dose strengths 150 and 300 μg. These in vitro results suggest that a minimum MIF of 60 L/min is required during routine use of Onbrez Breezhaler®, and confirm the good practice to make two separate inhalations from the same dose

Evaluation of sesamum gum as an excipient in matrix tablets

In developing countries modern medicines are often beyond the affordability of the majority of the population. This is due to the reliance on expensive imported raw materials despite the abundance of natural resources which could provide an equivalent or even an improved function. The aim of this study was to investigate the potential of sesamum gum (SG) extracted from the leaves of Sesamum radiatum (readily cultivated in sub-Saharan Africa) as a matrix former. Directly compressed matrix tablets were prepared from the extract and compared with similar matrices of HPMC (K4M) using theophylline as a model water soluble drug. The compaction, swelling, erosion and drug release from the matrices were studied in deionized water, 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) using USP apparatus II. The data from the swelling, erosion and drug release studies were also fitted into the respective mathematical models. Results showed that the matrices underwent a combination of swelling and erosion, with the swelling action being controlled by the rate of hydration in the medium. SG also controlled the release of theophylline similar to the HPMC and therefore may have use as an alternative excipient in regions where Sesamum radiatum can be easily cultivated

Novel spherical lactose produced by solid state crystallisation as a carrier for aerosolised salbutamol sulphate, beclomethasone dipropionate and fluticasone propionate

The purpose of the present work was to engineer lactose carrier particles for inhalation using a solid-state crystallisation of amorphous spray dried lactose approach. A suspension of spray dried lactose was contacted with hot ethanol for 10 and 30 s to produce spherical particles (ESDL10) and (ESDL30) with different degrees of crystallinity, particle size, and controlled surface rugosity. Lactohale® (control) and engineered spray dried lactose (ESDL) particles were characterised by Scanning Electron Microscopy, X-ray Powder Diffraction and Tribo-electrification. Lactohale® and engineered lactose particles were mixed separately with salbutamol sulphate (SS), beclomethasone dipropionate (BDP) and fluticasone propionate (FP) and each formulation was assessed for drug content uniformity, drug segregation after tribo-electrification and drug deposition using Andersen Cascade Impactor (ACI). Lactohale® showed the highest but opposite affinity for electrical surface charges compared to engineered lactose. Lactohale® showed the greatest variation in drug content uniformity with SS but to a lesser extent with BDP and FP, whereas the ESDL carriers produced an acceptable uniform mix with all drugs. SS-Lactohale® formulation showed the highest segregation after tribo-electrification up to 119-fold in comparison to that observed with SS-engineered lactose. ESDL10 carrier promoted a better drug deposition for both BDP and FP and showed the least variation in both content uniformity and FPD with all three drugs. Therefore, production of crystalline spherical lactose carrier with controlled surface texture, size and crystallinity is achievable using solid state crystallisation for DPIs, whilst providing less variation in drug content uniformity and consistent fine particle dose to the lungs in-vitro for both hydrophilic and hydrophobic drugs

Evaluation of the physicochemical properties and compaction behavior of melt granules produced in microwave-induced and conventional melt granulation in a single pot high shear processor

10.1208/s12249-011-9706-yAAPS PharmSciTech1241374-138