Category Archives: Eur J Pharm Biopharm

Can ‘extrafine’ dry powder aerosols improve lung deposition?

Eur J Pharm Biopharm. 2015 Jul 25;

Authors: de Boer AH, Gjaltema D, Hagedoorn P, Frijlink HW

Abstract
There is increasing interest in the use of so-called ‘extrafine’ aerosols to target the small airways in the management of asthma and COPD. Using previously presented deposition data, we assessed whether submicron (< 1 μm) particles can improve central and deep lung deposition. Our data show instead that particles in the range 1-3 μm are much more relevant in this respect. Based on this finding the Symbicort Turbuhaler, Seretide Diskus, Rolenium Elpenhaler and Foster (Fostair) NEXThaler ICS/LABA combination DPIs were tested in vitro as a function of the pressure drop (2, 4 and 6 kPa) across the inhaler. Obtained fine particle fractions (FPFs) < 5 μm (as percent of label claim) were divided into subfractions <1. 1-3 and 3-5 μm. Differences of up to a factor of 4 were found between the best (Turbuhaler) and worst performing DPI (Elpenhaler), particularly for the FPF in the size range 1-3 μm. The NEXThaler, described as delivering ‘extrafine’ particles, did not appear to be superior in this size range. The marked differences in amount and size distribution of the aerosols between the devices in this study must cause significant differences in the total lung dose and drug distribution over the airways.

PMID: 26220014 [PubMed – as supplied by publisher]

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Comparison of adjuvants for a spray freeze-dried whole inactivated virus influenza vaccine for pulmonary administration.
Eur J Pharm Biopharm. 2015 Apr 17;
Authors: Patil HP, Murugappan S, Vries-Idema J, Meijerhof T,… Continue reading →

Sunitinib microspheres based on [PDLLA-PEG-PDLLA]-b-PLLA multi-block copolymers for ocular drug delivery.

Eur J Pharm Biopharm. 2015 Feb 18;

Authors: Ramazani F, Hiemstra C, Steendam R, Kazazi-Hyseni F, Van Nostrum CF, Storm G, Kiessling F, Lammers T, Hennink WE, Kok RJ

Abstract
Sunitinib is a multi-targeted receptor tyrosine kinase (RTK) inhibitor that blocks several angiogenesis related pathways. The aim of this study was to develop sunitinib-loaded polymeric microspheres that can be used as intravitreal formulation for the treatment of ocular diseases. A series of novel multi-block copolymers composed of amorphous blocks of poly-(d,l-lactide) (PDLLA) and polyethylene glycol (PEG) and of semi-crystalline poly-(l-lactide) (PLLA) blocks were synthesized. Sunitinib-loaded microspheres were prepared by a single emulsion method using dichloromethane as volatile solvent and DMSO as co-solvent. SEM images showed that the prepared microspheres (∼30 μm) were spherical with a non-porous surface. Sunitinib-loaded microspheres were studied for their degradation and in-vitro release behavior. It was found that increasing the percentage of amorphous soft blocks from 10% to 30% accelerated the degradation of the multi-block copolymers. Sunitinib microspheres released their cargo for a period of at least 210 days by a combination of diffusion and polymer erosion. The initial burst (release in 24h) and release rate could be tailored by controlling the PEG-content of the multi-block copolymers. Sunitinib-loaded microspheres suppressed angiogenesis in a chicken chorioallantoic membrane (CAM) assay. These microspheres therefore hold promise for long-term suppression of ocular neovascularization.

PMID: 25701807 [PubMed – as supplied by publisher]

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The Cyclops for pulmonary delivery of aminoglycosides; a new member of the Twincer™ family.

Eur J Pharm Biopharm. 2015 Jan 20;

Authors: Hoppentocht M, Akkerman OW, Hagedoorn P, Frijlink HW, de Boer AH

Abstract
Patients infected with pathogenic bacteria have to be treated with antibiotics. When the infection is in the lungs, as for instance in cystic fibrosis, bronchiectasis and tuberculosis, inhaled antibiotics have certain advantages over systemically administered antibiotics. In this study, it is shown that re-designing the Twincer™ high dose disposable inhaler into a device named Cyclops enables effective dispersion of up to 50 mg of pure spray dried tobramycin. This proves that spray dried tobramycin powders in the preferred size range for inhalation can be administered without applying complex particle engineering techniques and/or using excipients. Only some coarse sweeper crystals added separately are desired to minimise the inhaler losses to less than 20% at 4 kPa. The fine particle fractions < 5 μm of the aerosol obtained from the Cyclops closely resemble the primary particle size distribution of the spray dried tobramycin powder. Moreover, without any further optimisation the Cyclops performs good with other spray dried aminoglycosides like kanamycin and amikacin too. Therefore, the results of this study show that with an appropriate inhaler design, adapted to the physico-chemical properties of a particular drug or drug class, excellent dispersion can be achieved for high doses of pure (spray dried) drug.

PMID: 25615881 [PubMed – as supplied by publisher]

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