Challenges for pulmonary delivery of high powder doses

In recent years there is an increasing interest in the pulmonary delivery of large cohesive powder doses, i.e. drugs with a low potency such as antibiotics or drugs with a high potency that need a substantial fraction of excipient(s) such as vaccines stabilized in sugar glasses. The pulmonary delivery of high powder doses comes with unique challenges. For low potency drugs, the use of excipients should be minimized to limit the powder mass to be inhaled as much as possible. To achieve this objective the inhaler design should be adapted to the properties of the API in order to achieve a compatible combination of the drug formulation and inhaler device. The inhaler should have an appropriate powder dosing principle for which prefilled compartments seem most appropriate. The drug formulation should not only allow for accurate filling of these compartments but also enable efficient compartment emptying during inhalation. The dispersion principle must have the capacity to disperse considerable amounts of powder in a short time frame that allows the powder to reach the deep lung. Last, but not least, the inhaler should be simple and intuitive in use, be cost-effective and exhibit accurate and consistent, preferably patient independent, pulmonary delivery performance

Optimisation of dry powder inhalation : the application of air classifier and laser diffraction technology for the generation and characterisation of aerosols from adhesive mixtures

Inhalatiegeneesmiddelen worden gegeven in doseringen variërend van enkele microgrammen tot enkele honderden milligrammen. Een gemiddelde poederdosis van 400 microgram (µg) heeft de grootte van een enkel suikerkristal. Om hieruit deeltjes van 0.001 tot 0.005 mm te krijgen moet het kristal tot globaal 2 tot 8 miljoen kleinere deeltjes worden vermalen. Door de kleine deeltjesgrootte ontstaat een sterk klonterig en plakkerig poeder (erger dan poedersuiker), dat zonder toevoegingen van hulpstoffen niet in de juiste hoeveelheid aan de patiënt kan worden toegediend. De hulpstoffen verdunnen het geneesmiddel waardoor de gewenste dosering beter kan worden afgemeten en verbeteren ook de stromingseigenschappen van het poeder. Tijdens het inhaleren moeten de farmacondeeltjes echter weer worden losgemaakt van de dragerdeeltjes. Zowel de krachten in het mengsel, die tot klontering leiden, als de scheidingskrachten moeten tijdens de inhalatie dus goed kunnen worden gecontroleerd en op elkaar afgestemd. Anne de Boer deed onderzoek naar deze processen en ontwikkelde uiteindelijk een nieuw technologisch principe om de samengeklonterde poeders in een fijn verdeelde aërosol om te zetten die diep in de longen kan doordringen. Deze technologie is inmiddels in twee nieuwe inhalatoren verwerkt. De Novolizer® is een inhalator geschikt voor longziekten zoals astma en COPD. De Twincer® is een uiterst innovatieve (wegwerp)inhalator, die in vergelijking met de tot nog toe op de markt gebrachte inhalatoren een 10 tot 25 keer zo hoge dosis desintegreert met dezelfde effectiviteit bij slechts een kwart van de inhalatie inspanning. Toepassingen voor deze inhalator liggen bijvoorbeeld in de toediening van hoog gedoseerde antibiotica bij taaislijmziekte (Cystic Fibrosis: CF) en vaccins (o.a. tegen influenza en mazelen).

Dry powder inhaler and method for pulmonary inhalation of dry powder

A breath actuated dry powder inhaler (1), comprising a substantially disc shaped air circulation chamber (2) for de-agglomeration of entrained powdered medicament using the energy of the inspiratory air stream. The chamber has a substantially circular or polygonal sidewall (3) extending about a central axis (4) between top (5) and bottom walls (6) of the chamber so that the height (h) of the chamber is smaller than its diameter (d). A plurality of air supply channels (7) disposed about the circumference of the chamber, which channels extend from joint or separate air inlets and which channels enter the chamber substantially tangentially to its sidewall. At least one of the supply channels extends through a powder dose supply region (8) of the inhaler. The chamber further comprises an air outlet (9) axially extending from a discharge opening (10) in the centre of the top or bottom wall of the chamber and connects to a discharge channel (12) that extends to a mouthpiece (13). The inhaler comprises at least one further air circulation chamber for de-agglomeration of entrained powdered medicament, the chambers being connected to the mouthpiece in parallel

Powder formulation disintegrating system and method for dry powder

For improving efficiency of the application of medical powder formulations a disintegration means for dry powder inhalers is proposed, comprising a substantially cylindrical air circulation chamber (3) with a height being smaller than its diameter, and at least two air supply channels (2, 9) which enter the chamber (3) as tangents to its cylindrical wall (5) at generally opposite sides of this wall (5), suitable for creating a circular air flow pattern inside the chamber (3), both air channels (2, 9) either having different inlets or alternatively sharing the same inlet which is split up, so as to have one passageway (2) for traversing the dose measuring or dose supplying region of the inhaler for enabling the powder quantity of a single dose dragged into the circulation chamber (3) by air flowing through this passageway (2), and the other passageway to serve as a bypass channel (9) towards the circulation chamber (3) suitable for accelerating the particles and creating a more symmetrical flow pattern inside said chamber (3), and a method

Dry powder inhalation, part 1: Ancient history and precursors to modern dry powder inhalers

Introduction: Inhalation of herbs and other compounds has a long history but habits for medical treatment are intertwined with rituals to obtain hallucinatory effects and pleasurable sensations. Several examples of inhaled herbs, and the diseases they were used for, based on early translations of ancient manuscripts related to inhalation were found to be speculative and inconsistent with each other in literature. They needed to be reconsidered and verified with the original sources of information. Areas covered: Examples of ancient inhalation and the development of early dry powder inhalers up to and including the first half of the twentieth century. Databases used for literature about historic events, ancient habits, and ancient science, included SmartCat, JSTOR, and ANDAT; various facts were verified via personal communication with historians and custodians of historic manuscripts and artifacts. Expert opinion: Inhalation does not necessarily require active creation of inhalable aerosols, smokes or fumes. Inhaling ‘healthy air’ with volatile and gaseous components, or fine aerosols in pine forests, on volcano slopes and at the seaside must be considered as inhalation therapy too. From this viewpoint, inhalation therapy may have been much more common and widespread and have a longer history than is currently known from written evidence

Dry powder inhalation, part 2: the present and future

Introduction: The manufacture of modern dry powder inhalers (DPIs), starting with the Spinhaler (Fisons) in 1967, was only possible thanks to a series of technological developments in the 20th century, of which many started first around 1950. Not until then, it became possible to design and develop effective, cheap and mass-produced DPIs. The link between these technological developments and DPI development has never been presented and discussed before in reviews about the past and present of DPI technology. Areas covered: The diversity of currently used DPIs with single dose, multiple-unit dose and multi-dose DPIs is discussed, including the benefits and drawbacks of this diversity for correct use and the efficacy of the therapy. No specific databases or search engines otherwise than PubMed and Google have been used. Expert opinion: Considering the relatively poor efficacy regarding lung deposition of currently used DPIs, the high rates of incorrect inhaler use and inhalation errors and the poor adherence to the therapy with inhalers, much effort must be put in improving these shortcomings for future DPI designs. Delivered fine particle doses must be increased, correct inhaler handling must become more intuitive and simpler to perform, and the use of multiple inhalers must be avoided