Dry powders for oral inhalation free of lactose carrier particles

Abstract

Dry powder inhaler (DPI) products have traditionally comprised a simple formulation of micronised drug mixed with a carrier excipient, typically lactose monohydrate. The presence of the carrier is aimed at overcoming issues of poor flowability and dispersibility, associated with the cohesive nature of small, micronised active pharmaceutical ingredient (API) particles. Both the powder blend and the DPI device must be carefully designed so as to ensure detachment of the micronised drug from the carrier excipient on inhalation. Over the last two decades there has been a significant body of research undertaken on the design of carrier-free formulations for DPI products. Many of these formulations are based on sophisticated particle engineering techniques; a common aim in formulation design of carrier-free products being to reduce the intrinsic cohesion of the particles, while maximising dispersion and delivery from the inhaler. In tandem with the development of alternative formulations has been the development of devices designed to ensure the efficient delivery and dispersion of carrier-free powder on inhalation. In this review we examine approaches to both the powder formulation and inhaler design for carrier-free DPI products.

Powder Particles and Technologies for Medicine Delivery to the Respiratory System: Challenges and Opportunities

“…This frequently requires blending the API grains with additional powder. Anhydrous lactose or lactose monohydrate particles are typically used as the excipient, and it must have an optimized particle size and surface properties to ensure flowability and the required de-agglomeration of the blend upon aerosolization (Pilcer G. et al, 2012); -optionally, the suitable API powder can be prepared without the excipient (Healy A.M. et al, 2014). In that case, the powder should possess special properties which can be obtained by particle engineering methods (Kaialy W. and Nokhodchi A., 2015)-see section 3.1; -powder properties must be stable during the typical shelf lifetime of pharmaceutical products (typically 3 years); -the medical powder must be packed in capsules or blisters with suitable properties to guarantee their efficient emptying during inhalation (Martinelli F. et al, 2015).…”

Polymer-drug conjugates as inhalable drug delivery systems: A review

“…Only a few amino acids, sugars and some polyethylene glycols have been approved for use in inhalable products. This limited number of approved excipients can slow the development of inhalable polymer-drug conjugates as well as limit their clinical translation, since the use of new polymers and excipients will require extensive in vivo safety studies [15,126].…”

Characterisation of dry powder inhaler formulations using atomic force microscopy

“…The drug load itself also affects formulation performance along with the choice of inhaler device (De Boer et al, 2005) and the patient's individual breathing pattern (Chrystyn and Price, 2009;Heyder, 2004). The relationship between particulate characteristics and their respective effects on formulation performance have been studied and reviewed widely over the years (Adi et al, 2013;Chan, 2008;Chow et al, 2007;Donovan and Smyth, 2010;Guenette et al, 2009;Healy et al, 2014;Zellnitz et al, 2014;Zeng et al, 2000;Zhang et al, 2011).…”

“…To date, lactose tends to be the carrier material of choice-but researchers (Hooton et al, 2006b;Kaialy et al, 2011Kaialy et al, , 2010Nokhodchi, 2012, 2013a,b;Packhaeuser et al, 2009) are working towards the use of sugar based substitutes such as mannitol, raffinose, trehalose, xylitol and cyclodextrin; novel materials such as polymer nano-carriers (Paranjpe and Müller-Goymann, 2014); and the development of carrier free formulations (Healy et al, 2014). AFM has been used to evaluate the morphology of freeze-dried mannitol, a promising carrier species (Packhaeuser et al, 2009).…”