l -Leucine as an excipient against moisture on in vitro aerosolization performances of highly hygroscopic spray-dried powders

Li, Liang; Sun, Shanzhong; Parumasivam, Thaigarajan; Denman, John A.; Gengenbach, Thomas R.; Tang, Patricia A.; Mao, Shirui; Chan, Hak‐Kim

doi:10.1016/j.ejpb.2016.02.010

Cited by 151 publications

(77 citation statements)

References 31 publications

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“…Composite formulations showed the similar morphology to the Azithromycin-SD particles (Fig. 1b and c) rather than the spray dried L-leucine (47). Previous studies have shown that L-leucine could alter the morphology of some spray-dried particles due to enrichment of L-leucine on the particle surface (56).…”

Section: Resultsmentioning

confidence: 88%

“…Given amino acids’ weakly acidic nature, we hypothesized that formulating azithromycin with L-leucine may improve the solubility and dissolution of azithromycin by providing a more acidic environment. L-leucine has been extensively investigated in DPI formulations to reduce cohesion and improve aerosol performance (44–46) and moisture protection (47); however, its capability to improve dissolution of inhalable poorly water soluble DPI formulations has not been systemically examined. In the present study, we developed co-spray dried inhalable powder formulations consisting of azithromycin and L-leucine.…”

Section: Introductionmentioning

confidence: 99%

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Physico-Chemical Properties, Aerosolization and Dissolution of Co-Spray Dried Azithromycin Particles with L-Leucine for Inhalation

Mangal

Nie

et al. 2018

Pharm Res

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Purpose Inhalation therapy is popular to treat lower respiratory tract infections. Azithromycin is effective against some bacteria that cause respiratory tract infections; but it has poor water solubility that may limit its efficacy when administrated as inhalation therapy. In this study, dry powder inhaler formulations were developed by co-spray drying azithromycin with L-leucine with a purpose to improve dissolution. Methods The produced powder formulations were characterized regarding particle size, morphology, surface composition and in-vitro aerosolization performance. Effects of L-leucine on the solubility and in-vitro dissolution of azithromycin were also evaluated. Results The spray dried azithromycin alone formulation exhibited a satisfactory aerosol performance with a fine particle fraction (FPF) of 62.5 ± 4.1%. Addition of L-leucine in the formulation resulted in no significant change in particle morphology and FPF, which can be attributed to enrichment of azithromycin on the surfaces of composite particles. Importantly, compared with the spray-dried amorphous azithromycin alone powder, the co-spray dried powder formulations of azithromycin and L-leucine demonstrated a substantially enhanced in-vitro dissolution rate. Such enhanced dissolution of azithromycin could be attributed to the formation of composite system and the acidic microenvironment around azithromycin molecules created by the dissolution of acidic L-leucine in the co-spray dried powder. Fourier transform infrared spectroscopic data showed intermolecular interactions between azithromycin and L-leucine in the co-spray dried formulations. Conclusions We developed the dry powder formulations with satisfactory aerosol performance and enhanced dissolution for a poorly water soluble weak base, azithromycin, by co-spray drying with an amino acid, L-leucine.

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Section: Resultsmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Physico-Chemical Properties, Aerosolization and Dissolution of Co-Spray Dried Azithromycin Particles with L-Leucine for Inhalation

Mangal

Nie

et al. 2018

Pharm Res

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“…With further increase in leucine concentration, the aforementioned diffraction peaks became sharper and an additional peak was detected around 12°. Signal peak at 20° belongs to alpha-lactose monohydrate [29], whereas those at 6°, 12°, 25°, 31° and 34° belong to crystalline leucine [30]. Phage formulation spray dried from solution containing 17 mg/mL trehalose and 8 mg/mL leucine gave sharper diffraction peaks than those with 17 mg/mL lactose and 8 mg/mL leucine.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, leucine can also impart stability against moisture for spray dried inhalable powders stored at elevated RH [30, 38]. In the absence of leucine, spray dried phage powders formed large agglomerates unsuitable for inhalation (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Our results have shown improved FPF with the presence of leucine, and increasing the leucine content in phage formulation beyond 32 % (w/w) did not affect the in vitro aerosol performance (Table 7). This is probably due to plateauing of the surface concentration of leucine when the concentration exceeded 20% (v/v) in the feed concentration [30]. Instead, the addition of Pluronic F68, a surfactant, further enhanced the FPF of phage formulation…”

Section: Discussionmentioning

confidence: 99%

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Production of highly stable spray dried phage formulations for treatment of Pseudomonas aeruginosa lung infection

Chang

Wong

Mathai

et al. 2017

European Journal of Pharmaceutics and Biopharmaceutics

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The potential of bacteriophage therapy for the treatment of pulmonary infections caused by antibiotic-resistant bacteria has been well recognised. The purpose of this study was to investigate the effect of excipients on stabilisation and aerosolisation of spray dried powders of morphologically different phages – PEV podovirus and PEV myovirus. Seven anti-pseudomonal phages were screened against 90 clinical strains of bacterial hosts and three of the phages were selected for formulation study based on the host range. Design of experiments was utilised to assess the effect of different excipients on the stabilisation and aerosolisation of spray dried phages. Both podovirus and myovirus phages were stable in spray dried formulations containing trehalose or lactose and leucine as excipients with less than 1-log10 titre reduction during spray drying, with lactose providing superior phage protection over trehalose. Furthermore, the spray dried phage formulations dispersed in an Osmohaler at 85 L/min produced a high fine particle fraction of over 50 %. The results showed that the phages in this study can form respirable dry powder phage formulations using the same excipient composition. Spray dried various types of lytic phages hold significant potential for the treatment of pulmonary infections.

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Dry Powder Coating Techniques and Role of Force Controlling Agents in Aerosol

et al. 2020

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l -Leucine as an excipient against moisture on in vitro aerosolization performances of highly hygroscopic spray-dried powders

Cited by 151 publications

References 31 publications

Physico-Chemical Properties, Aerosolization and Dissolution of Co-Spray Dried Azithromycin Particles with L-Leucine for Inhalation

Physico-Chemical Properties, Aerosolization and Dissolution of Co-Spray Dried Azithromycin Particles with L-Leucine for Inhalation

Production of highly stable spray dried phage formulations for treatment of Pseudomonas aeruginosa lung infection

Dry Powder Coating Techniques and Role of Force Controlling Agents in Aerosol

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