The enhanced aerosol performance of salbutamol from dry powders containing engineered mannitol as excipient.

Published on Jun 15, 2010in International Journal of Pharmaceutics5.875
· DOI :10.1016/J.IJPHARM.2010.03.057
Waseem Kaialy23
Estimated H-index: 23
(Medway School of Pharmacy),
Gary P. Martin61
Estimated H-index: 61
('KCL': King's College London)
+ 2 AuthorsAli Nokhodchi63
Estimated H-index: 63
(Tabriz University of Medical Sciences)
Sources
Abstract
The aim of the present study was to investigate the effect of crystallising mannitol from different binary mixtures of acetone/water on the resultant physical properties and to determine the effects of any changes on in vitro aerosolisation performance, when the different mannitol crystals were used as a carrier in dry powder inhaler formulations containing salbutamol sulphate. Mannitol particles were crystallised under controlled conditions by dissolving the sugar in water and precipitating the sugar using binary mixtures of acetone/water in different percentages as anti-solvent media. For comparison purposes the physical properties and deposition behaviour of commercially available mannitol were also studied. SEM showed that all crystallised mannitol particles were more elongated than the commercial mannitol. Solid state studies revealed that commercial mannitol and mannitol crystallised using acetone in the presence of 10-25% v/v water as anti-solvent was β-polymorphic form whereas mannitol crystallised in the presence of a small amount of water (0-7.5%) was the α-form. All the crystallised mannitol samples showed poor flowability. Nevertheless, the powdered crystallised mannitol and commercial samples were blended with salbutamol in the ratio 67.5:1. The aerosolisation performance of the formulations containing the engineered mannitol (evaluated using Multi Stage Liquid Impinger) was considerably better than that of the commercial mannitol formulation (the fine particle fraction was increased from 15.42% to 33.07-43.99%, for the formulations containing crystallised mannitol). Generally, carriers having a high tapped density and high fraction of fine carrier particles produced a high FPF. The improvement in the DPI performance could be attributed to the presence of elongated carrier particles with smooth surfaces since these are believed to have less adhesive forces between carrier and the drug resulting in easier detachment of the drug during the inhalation. © 2010 Elsevier B.V.
📖 Papers frequently viewed together
20114.01Aaps Journal
7 Authors (Waseem Kaialy, ..., Ali Nokhodchi)
References26
Newest
#1G. Saint-LorantH-Index: 1
#2P. LetermeH-Index: 10
Last. M.P. FlamentH-Index: 10
view all 4 authors...
Abstract The aim of this work is to study carriers which can become alternatives to monohydrate lactose in dry powder inhalers and to consider particle parameters that influence adhesion between drug and carrier in dry powder inhalers. Different forms of mannitol, lactose and maltitol were mixed with either terbutaline sulphate or formoterol fumarate. The blends were submitted to different adhesion tests where drug detachment from the carrier was obtained either through mechanical vibration or b...
Source
#1Naumana R. Rabbani (Aston University)H-Index: 1
#2Peter C. Seville (Aston University)H-Index: 14
Dry powders suitable for inhalation containing β-estradiol, leucine as a dispersibility enhancer and lactose as a bulking agent were prepared by spray-drying from aqueous ethanol formulations. The influence of formulation components on the characteristics of the resultant spray-dried powders was examined through the use of a range of ethanol concentrations (10-50% v/v) in the solvent used to prepare the initial formulations. Additionally, the amount of leucine required to act as a dispersibility...
Source
#1Hugh D. C. Smyth (UNC: University of North Carolina at Chapel Hill)H-Index: 34
#2Anthony J. Hickey (UNC: University of North Carolina at Chapel Hill)H-Index: 61
The performance of dry powder inhaler (DPI) systems depends on the design of the powder formulation, the dose-metering system, and the device used to disperse the powder as an aerosol. Multiple factors associated with drug and carrier particles are known to influence dry powder performance. Elucidation of a mechanistic understanding of particulate system properties and how these relate to powder performance and the disruption of inter-particulate forces that cause aggregation has not yet been ac...
Source
#1B.H.J. Dickhoff (UG: University of Groningen)H-Index: 6
#2de Anne Boer (UG: University of Groningen)H-Index: 19
Last. Henderik W. Frijlink (UG: University of Groningen)H-Index: 69
view all 4 authors...
Abstract The effectiveness of press-on forces (defined as the adhesive forces between drug and carrier particles) in relation to carrier payload as the result of collisions between carrier particles during the mixing process of an adhesive mixture, has been investigated. Three different carriers of the same size fraction (250–355 μm), but with completely different surface rugosity were studied. It could be shown that this effectiveness depends on the carrier rugosity. The fraction of drug detach...
Source
#1Nazrul Islam (Monash University, Parkville campus)H-Index: 41
#2Peter Stewart (Monash University, Parkville campus)H-Index: 32
Last. Patrick G. Hartley (CSIRO: Commonwealth Scientific and Industrial Research Organisation)H-Index: 38
view all 4 authors...
Purpose. The role of fine lactose in the dispersion of salmeterol xina- foate (SX) from lactose mixtures was studied by modifying the fine lactose concentration on the surface of the lactose carriers using wet decantation.
Source
Abstract Most dry powder inhaler (DPI) formulations rely on lactose monohydrate as a carrier in the drug powder blends. However, lactose cannot be used for compounds that interact with the reducing sugar function of the lactose, such as formoterol, budesonide or peptides and proteins. In this study, alternative carriers like mannitol, glucose, sorbitol, maltitol and xylitol have therefore been evaluated for their potential use in DPI formulations. Raw materials were characterised physico-chemica...
Source
Abstract The effect of carrier payload and mixing time on the redispersion of drug particles from adhesive mixtures during inhalation for two different drugs (budesonide and disodium cromoglycate) has been investigated. A special test inhaler which retains carrier crystals during inhalation was used at 30 and 60 l/min. The special inhaler enabled the analysis of residual drug on the carrier yielding so called carrier residue (CR) values. Mixtures with carrier size fractions of 32–45; 150–200 and...
Source
#1Hak-Kim Chan (USYD: University of Sydney)H-Index: 76
#2Nora Y.K. Chew (USYD: University of Sydney)H-Index: 17
Successful delivery of dry powder aerosols to the lung requires careful consideration of the powder production process, formulation and inhaler device. Newer production methods are emerging to prepare powders with desirable characteristics for inhalational administration. The conventional formulation approach of adding coarse lactose carriers to the drug to form binary powder systems to enhance powder flow and dispersion properties has been expanded to using finer carrier particles and hydrophob...
Source
#1Hassan Larhrib ('KCL': King's College London)H-Index: 14
#2Gary P. Martin ('KCL': King's College London)H-Index: 61
Last. David Prime (GSK: GlaxoSmithKline)H-Index: 4
view all 4 authors...
Abstract Lactose was crystallised either from neutralised Carbopol 934 gel or from water–ethanol solution without stirring, with a view to obtaining lactose α-monohydrate of favourable shape and smooth surface, suitable for use as carriers in formulations for dry powder inhalers (DPIs). Crystallisation of salbutamol sulphate was carried out in the presence of water, lecithin and ethanol to form salbutamol crystals with defined shape and smooth surface. The crystals formed were needle-shaped, wit...
Source
Abstract The effects of moisture on the polymorphic transition of crystalline mannitol were investigated. Mannitol has three polymorphic forms, and was classified as α, β, and δ form, respectively, by Walter-Levy (C.R. Acad. Sc. Paris Ser. C (1968) 267, 1779). The water uptake of δ form crystalline was greater than that of the β form when each crystalline form was stored at 97%RH (25 °C). The different powder X-ray diffraction patterns obtained before and after humidification confirmed that a mo...
Source
Cited By57
Newest
#1Ashutosh Sharma (WIT: Waterford Institute of Technology)H-Index: 1
Last. Helen Hughes (WIT: Waterford Institute of Technology)H-Index: 21
view all 5 authors...
In the past two decades, biopharmaceuticals have been a breakthrough in improving the quality of lives of patients with various cancers, autoimmune, genetic disorders etc. With the growing demand of biopharmaceuticals, the need for reducing manufacturing costs is essential without compromising on the safety, quality, and efficacy of products. Batch Freeze-drying is the primary commercial means of manufacturing solid biopharmaceuticals. However, Freeze-drying is an economically unfriendly means o...
Source
#1Laura Nižić Nodilo (University of Zagreb)H-Index: 1
#2Ivo Ugrina (University of Split)H-Index: 13
Last. Anita Hafner (University of Zagreb)H-Index: 16
view all 13 authors...
Nasal route of administration offers a unique opportunity of brain targeted drug delivery via olfactory and trigeminal pathway, providing effective CNS concentrations at lower doses and lower risk for adverse reactions compared to systemic drug administration. Therefore, it has been recently proposed as a route of choice for glucocorticoids to control neuroinflammation processes in patients with severe Covid-19. However, appropriate delivery systems tailored to enhance their efficacy yet need to...
Source
#1Hsien-Tsung Wu (MCUT: Ming Chi University of Technology)H-Index: 2
#2Tsung-Hsuan Li (MCUT: Ming Chi University of Technology)H-Index: 2
Last. Yao-Hsiang Chuang (MCUT: Ming Chi University of Technology)H-Index: 1
view all 5 authors...
Abstract Mannitol carrier and drug-carrier composite particles were produced via low-temperature supercritical assisted atomization (LTSAA). The enhanced aerosolization of the mannitol carrier particles with added L-leucine could be attributed to the formation of fine corrugated particles, which reduced the interparticle cohesion and led to better flowability of the mannitol carrier particles. A poorly water-soluble drug, beclomethasone dipropionate (BDP), and mannitol co-precipitated during LTS...
Source
#1Mickey Socrates Ferdynand (University of Sussex)H-Index: 1
#2Ali Nokhodchi (University of Sussex)H-Index: 63
Although in dry powder inhaler (DPI) formulations a single carrier is used, a single carrier is not able to provide an excellent aerosolization performance when it is used in DPI formulations. Thereby, the aim of this study was to engineer a suitable ternary mixture of mannitol-lactose-leucine to be used in a DPI formulation with enhanced aerosolization performance. To this end, binary mixtures of mannitol:lactose containing a constant amount of leucine (5% w/w of carriers) were spray-dried as a...
Source
#1Piyush Mehta (Poona College of Arts Science & Commerce)H-Index: 15
#2Shivajirao S. Kadam (Alka)H-Index: 25
Last. Atmaram Pawar (Poona College of Arts Science & Commerce)H-Index: 25
view all 3 authors...
Abstract The present study aimed to probe influences exerted by extrinsic lactose fines on drug detachment and delivered dose uniformity (DDU) of fluticasone propionate (FP) dry powder inhaler (DPI). Extrinsic lactose fines (0–35%) containing lactose pre-blends were formulated using a low shear 3D shaker mixer and systematically analyzed for various physicochemical properties. Moreover, formulated FP DPIs were assessed for drug detachment by force distribution concept and the DDU using two diffe...
Source
#1Carlos Molina (University of Sussex)H-Index: 3
#2Waseem Kaialy (University of Wolverhampton)H-Index: 23
Last. Ali Nokhodchi (University of Sussex)H-Index: 63
view all 3 authors...
Generally, DPI formulations show low fine particle fraction (FPF) due to poor detachment of drug particles from carrier during inhalation. L-Leucine, with varying concentrations (ranging from 0 to 10% w/w), were introduced into a 60%w/v mannitol solution where the solutions were then spray dried to achieve a new processed carrier. The spray dried samples were blended with Albuterol sulfate to determine the efficacy of their aerosolization performance. Analyzing each formulation was completed via...
Source
#1Mohammad Ashfaq (IITK: Indian Institute of Technology Kanpur)H-Index: 12
#2Nishith Verma (IITK: Indian Institute of Technology Kanpur)H-Index: 38
Last. Suphiya Khan (Banasthali Vidyapith)H-Index: 12
view all 3 authors...
Abstract A cellulose acetate phthalate (CAP)-mannitol copolymer dispersed in the polyvinly alcohol (PVA) film was in situ mixed with the copper (Cu) metal nanoparticle (NP)-dispersed carbon nanofibers (CNFs). The synthesized polymer-metal-carbon nanocomposite was efficiently used as the chemiresistive sensor material for determining the quality (freshness) of banana via the measurement of electrical current during the release of ethylene (C2H4) gas from the banana samples. The prepared material ...
Source
Inhalation therapy has strong history of more than 4000 years and it is well recognized around the globe within every culture. In early days, inhalation therapy was designed for treatment of local disorders such as asthma and other pulmonary diseases. Almost all inhalation products composed a simple formulation of a carrier, usually α-lactose monohydrate orderly mixed with micronized therapeutic agent. Most of these formulations lacked satisfactory pulmonary deposition and dispersion. Thus, vari...
Source
#1Tingting Peng (SYSU: Sun Yat-sen University)H-Index: 11
#2Xuejuan Zhang (SYSU: Sun Yat-sen University)H-Index: 7
Last. Chuanbin WuH-Index: 33
view all 11 authors...
Nanoporous mannitol carrier prepared by non-organic solvent spray drying technique to enhance the aerosolization performance for dry powder inhalation
Source
#1Xiang Kou (NUS: National University of Singapore)H-Index: 4
#2Lai Wah Chan (NUS: National University of Singapore)H-Index: 33
Last. Paul Wan Sia Heng (NUS: National University of Singapore)H-Index: 54
view all 4 authors...
Abstract Dry powder inhalers are often formulated by attaching micronized drug particles onto carrier particles, which are generally lactose. In this study, commercially available lactose was air jet milled to produce unique slab-like coarse carrier particles, which have larger and rougher surfaces compared to other commercially available lactose. Two key processing factors, i.e., classifier speed and jet milling pressure, were systematically investigated. The largest fraction of slab-like parti...
Source
This website uses cookies.
We use cookies to improve your online experience. By continuing to use our website we assume you agree to the placement of these cookies.
To learn more, you can find in our Privacy Policy.