Nanospray Drying as a Novel Technique for the Manufacturing of Inhalable NSAID Powders

Abstract

The aim of this research was to evaluate the potential of the nanospray drier as a novel apparatus for the manufacturing of a dry powder for inhalation containing ketoprofen lysinate, a nonsteroidal anti-inflammatory drug able to control the inflammation in cystic fibrosis patients. We produced several ketoprofen lysinate and leucine powder batches by means of nanospray dryer, studying the influence of process parameters on yield, particle properties (size distribution and morphology), and, mainly, aerodynamic properties of powders. Micronized particles were prepared from different hydroalcoholic solutions (alcohol content from 0 to 30% v/v) using ketoprofen in its lysine salt form and leucine as dispersibility enhancer in different ratios (from 5 to 15% w/w) with a total solid concentration ranging from 1 to 7% w/v. Results indicated that the spray head equipped with a 7 µm nozzle produced powders too big to be inhaled. The reduction of nozzle size from 7 to 4 µm led to smaller particles suitable for inhalation but, at the same time, caused a dramatic increase in process time. The selection of process variables, together with the nozzle pretreatment with a surfactant solution, allowed us to obtain a free flowing powder with satisfying aerosol performance, confirming the usefulness of the nanospray drier in the production of powder for inhalation.

Potential Nanospray Inhalation of Remdesivir and Hydroxychloroquine using Poly (lactic-co-glycolic) Acid as Fast Delivery for Covid-19 Treatment.

“…There are two types of spray dryers available in the market nowadays; standard spray dryer and nanospray dryer. A standard spray dryer uses a pneumatic nozzle system while a nanospray dryer uses a piezoelectric system to produce liquid feed droplets by spraying the starting liquid material containing the drug into a hot drying medium (Patrizia et al, 2014). A standard spray-drying procedure comprises of four steps which are 1) atomisation of the liquid feed, 2) evaporating of the liquid feed through the drying gas, 3) formation of a particle, and lastly 4) separation and collection of the formed particle (Arpagaus, 2019b;Schafroth et al, 2012).…”

“…Interestingly, the innovative nano spray dryer has become a more promising technology to produce powder particles for inhalation as compared to standard spray dryers because of its ability in controlling and reducing powder particles (Patrizia et al, 2014). Nanospray dryer could produce liquid droplets using a piezoelectric system that functions at a certain ultrasonic frequency (60 kHz) and thus forming a mist of droplets that has a remarkable ultra-fine particle size.…”

“…This membrane has several specific micron-sized holes (spray meshes with hole sizes of 4.0, 5.5, or 7.0 µm) to generate small particles (size ranging from 3 to 15 µm) in a very narrow size distribution. Last but not least, the novel spray dryer has an electrode collector that collects particles electrostatically charged to produce high yields and thus reduce particle wastages (Arpagaus, 2012;Patrizia et al, 2014;Schafroth et al, 2012). The advantages of nanospray drying are 1) particle size and shape optimization for pulmonary drug delivery, 2) high bioavailability of the drug in the lungs as compared to oral administration, 3) reduction of drug doses, 4) minimizing systemic side effects, and 5) increases patient adherence (Arpagaus, 2012(Arpagaus, , 2019bArpagaus et al, 2018).…”

“…The nozzle spray pretreated with a surfactant solution (leucine) could generate a free-flowing powder with a satisfactory aerosol functioning. This could be beneficial for the nanospray dryer to produce efficient powder for inhalation (Patrizia et al, 2014). The encapsulated product must be kept under a controlled condition and a stabilizer may be added into the feed formulation to maintain its activity after nanospray drying.…”

A Novel Combined Dry Powder Inhaler Comprising Nanosized Ketoprofen-Embedded Mannitol-Coated Microparticles for Pulmonary Inflammations: Development, In Vitro–In Silico Characterization, and Cell Line Evaluation

“…KETO is available on the market for oral, topical, and rectal administration but not for pulmonary administration (https://go.drugbank.com/drugs/DB01009, accessed on 28 May 2023). Nevertheless, a few studies have been conducted to develop KETO for inhalation in its salt form (ketoprofen lysinate) by a single step of co-spray drying with leucine [16,17]. D-Mannitol (MAN) is categorized as a sugar alcohol that can work as an osmotic agent [18].…”