Cospray Dried Antibiotics for Dry Powder Lung Delivery

doi:10.1002/jps.21239

Journal of Pharmaceutical Sciences

Volume 97, Issue 8, August 2008, Pages 3356-3366

https://doi.org/10.1002/jps.21239 Get rights and content

ABSTRACT

The aim of this study was to assess the potential of delivering a combination antibiotic therapy, containing doxycycline and ciprofloxacin (both hydrochloride) as a dry powder (DPI) formulation for inhalation. Single and combination antibiotics were produced by spray drying. Particle size distributions were characterized by laser diffraction and imaging conducted by scanning electron microscopy. Solid-state characterisation of the antibiotics was carried out using differential scanning calorimetry, dynamic vapour sorption, X-ray powder diffraction, and differential scanning calorimetry. Using the Aerolizer® device, the aerosol performance was measured using multistage liquid impinger and analysed using high performance liquid chromatography (R² = 1.0, CV = 0.4–1.0%). Furthermore, a disk diffusion test was performed for the assessment of the in vitro antimicrobial activity of the raw and spray dried antibiotics against bacteria. Results showed that cospray drying of the ciprofloxacin and doxycycline produced an antibiotic formulation (in a 1:1 ratio) suitable for inhalation that showed to be physically more stable then the analogous single spray dried antibiotic. The cospray dried powder has improved dispersion over the less stable single spray dried ciprofloxacin. The spray dried antibiotics were observed to have similar antimicrobial activity to the original antibiotics for Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pyrogenes, suggesting the spray drying process does not affect the anti-bacterial activity of the drug. Cospray dried antibiotics from a DPI is thus feasible and can potentially be an attractive delivery alternative to the more conventional systemic delivery route.

Section snippets

INTRODUCTION

Delivery of antibiotics via the pulmonary tract to treat respiratory infection, such as pneumonia, is advantageous over more conventional routes, since the lungs are directly targeted. Using targeted delivery, the therapeutic dose may be lower, leading to a decrease in potential drug resistance build-up and reduction in side effects, often associated with high oral doses. Currently antibiotic inhalation therapy is limited to small volume nebulisers,¹ which are cumbersome, expensive and require

Materials

Ciprofloxacin and doxycycline (both hydrochlorides) were chosen as model antibiotics and used as supplied (MP, Biomedical Australasia Pty Limited, Seven Hills, NSW, Australia). Water was purified by reverse osmosis (MilliQ, Millipore, France). All solvents were obtained from Biolab (Clayton, Victoria, Australia) and were of analytical grade. The model bacteria used in this study were Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pyogenes (all strains were obtained from the

RESULTS AND DISCUSSION

In order to understand the aerosol properties of the combination formulation the study was divided into two primary sections: (1) physical characterisation of formulation and (2) in vitro characterisation of the antibiotics formulation.

CONCLUSIONS

In this study the authors investigated the physical stability and aerosolisation efficiency of a cospray dried antibiotic formulation containing ciprofloxacin and doxycycline as a dry powder inhaler formulation providing a feasible and potentially attractive alternative to nebulisation or oral and systemic dosage. The combination of these particular two chemical entities as a cospray dried formulation suggested that a physically stable powder could be produced that facilitated simultaneous and

ACKNOWLEDGEMENTS

The authors would like to thank the Pharmacy Trust of New South Wales for the monetary support.

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Research ArticlesCospray Dried Antibiotics for Dry Powder Lung Delivery

ABSTRACT

Section snippets

INTRODUCTION

Materials

RESULTS AND DISCUSSION

CONCLUSIONS

ACKNOWLEDGEMENTS

Chest

J Pediatr

Lancet

Int J Pharm

Eur J Pharm Biopharm

Eur J Pharm Biopharm

Chest

J Cyst Fibros

Int J Pharm

Eur J Pharm Sci

J Pharm Sci

J Pharm Sci

Chest

Eur J Pharm Sci

Effect of nebuliser type and antibiotic concentration on device performance

Pediatr Pulmonol

Influence of breathing pattern on lung deposition and bronchodilator response to nebulized salbutamol in patients with stable asthma

Thorax

Quantitative deposition of aerosolized gentamicin in cystic fibrosis

Am Rev Respir Dis

Evaluation of jet nebulisers for use with gentamicyn solution

Thorax

Research Articles
Cospray Dried Antibiotics for Dry Powder Lung Delivery