Assessment of Dry Powder Inhaler Carrier Targeted Design: A Comparative Case Study of Diverse Anomeric Compositions and Physical Properties of Lactose

Abstract

The pulmonary administration landscape has rapidly advanced in recent years. Targeted design of particles by spray-drying for dry powder inhaler development offers an invaluable tool for engineering of new carriers. In this work, different formulation and process aspects of spray-drying were exploited to produce new lactose carriers. Using an integrated approach, lactose was spray-dried in the presence of polyethylene glycol 200 (PEG 200), and the in vitro performance of the resulting particles was compared with other grades of lactose with varying anomeric compositions and/or physical properties. The anomeric composition of lactose in lactose-PEG 200 feed solutions of variable compositions was analyzed via polarimetry at different temperatures. These results were correlated with the solid-state and anomeric composition of the resulting spray-dried particles using modulated differential scanning calorimetry and wide-angle X-ray scattering. The distinct selected grades of lactose were characterized in terms of their micromeritic properties using laser diffraction, helium pycnometry, and gas adsorption, and their particle surface morphologies were evaluated via scanning electron microscopy. Adhesive mixtures of the different lactose carriers with inhalable-sized salbutamol sulfate, as a model drug, were prepared in low doses and evaluated for their blend homogeneity and aerodynamic performance using a Next Generation Impactor. Characterization of the spray-dried particles revealed that predominantly crystalline (in an anomeric ratio 0.8:1 of α to β) spherical particles with a mean size of 50.9 ± 0.4 μm could be produced. Finally, it was apparent that micromeritic, in particular, the shape, and surface properties (inherent to solid-state and anomeric composition) of carrier particles dominantly control DPI delivery. This provided an insight into the relatively inferior performance of the adhesive blends containing the spherical spray-dried lactose-PEG 200 composites.

Understanding Carrier Performance in Low-Dose Dry Powder Inhalation: An In Vitro–In Silico Approach

“…Micronized salbutamol sulphate (racemic mixture, Fagron GmbH & Co., Glinde, Germany) with a particle size of Dv 0.1 = 0.43 ± 0.01 µm, Dv 0.5 = 1.53 ± 0.07 µm and Dv 0.9 = 3.79 ± 0.26 µm was chosen as a model API. In line with our previous work [1], Duralac © H (16% α anomer and 83.5% β anomer, Meggle, Wasserburg am Inn, Germany), αlactose monohydrate Flowlac © 90 (β anomer ≤ 3%, Meggle, Wasserburg am Inn, Germany), Respitose © SV003 (β anomer ≤ 3%, DFE pharma, Goch, Germany) and Lactohale © 100 (β anomer ≤ 3%, DFE pharma, Goch, Germany), were used as model carriers. Flowlac ® 90 was dry sieved using a vibratory sieve shaker (Retsch AS200, Germany) to obtain its 20-90 µm particle size fraction.…”

“…For the sandwich, the API was placed between two even layers of lactose, and the half-filled vessels blended in a Turbula blender TC2 (Willy A. Bachofen Maschinenfabrik, Muttenz, Switzerland) for 90 min at 62 rpm. The homogeneity of the blends was confirmed as previously described [1,5], and characterization of the mixtures was only carried out once a homogenous sample was obtained.…”

“…Dry powder inhalers (DPIs) are dosage forms used to deliver drugs to the lung. It is generally accepted that the active pharmaceutical ingredient (API) particles must have a size between 1 and 5 µm to enter the respiratory tract and deposit on the bronchio-alveolar epithelium [1]. Due to their large specific surface area, inhalable drug particles are very cohesive, present poor flowability and are a challenge to process in order to be efficiently delivered to the lung.…”

A review on chitosan and its development as pulmonary particulate anti-infective and anti-cancer drug carriers

“…Lactose receives a widespread application in the development of inhalation medicine specifically with respect to dry powder aerosol ( Lee et al, 2018 ; Molina et al, 2018 ; Pinto et al, 2018 ; Zhou & Morton, 2012 ). This is attributed to stability, better flow properties and safety of lactose in dry powder inhaler formulations ( Smyth & Hickey, 2005 ).…”

Probing Critical Physical Properties of Lactose-Polyethylene Glycol Microparticles in Pulmonary Delivery of Chitosan Nanoparticles

“…Lactose is widely used in inhalation dosage form development with reference to dry powder aerosol [1][2][3][4]. It is safe, and exhibits good physicochemical stability and powder flow properties [5].…”