Bevacizumab for Intravitreal Injection: Impact of Sub-Visible Particles on the Shelf-Life of Repackaged Bevacizumab.

Purpose: Bevacizumab (Avastin) is a humanized monoclonal antibody approved by the European Medicines Agency for the intravenous treatment of cancer. However, it is often used as an intravitreal injection for the treatment of macular degeneration or edema. For this purpose, bevacizumab is repackaged from glass vials into plastic syringes. The formation of particles during this compounding process as well as during storage is a source of concern. The aim of this study was to test the sub-visible particulate contamination in bevacizumab material, both in the glass vial and after repackaging into polycarbonate BD Luer-Lok™ syringes. Methods: Syringes with repackaged bevacizumab from 3 different compounding hospital pharmacies were tested for sub-visible particles at different time points during storage at 2-8°C. Results: The batches of bevacizumab starting product complied with the European Pharmacopoeia (Ph. Eur.) for small-volume parenterals. Repackaging into syringes led to an immediate increase in small particles. The number of particles ≥25 µm increased 1.3-fold, and the number of particles ≥10 µm increased 5-fold, respectively. Storage of up to 37 days did not lead to an additional increase in particle counts. All batches complied with the national criteria for particles in intravitreal solutions. Conclusions: Particle count increased due to the repackaging process, but no substantial increase was observed during storage. Formation of sub-visible particles does not impact the shelf-life of bevacizumab repackaged into BD Luer-Lok syringes.

Ready-to-use parenteral amiodarone: a feasibility study towards a long-term stable product formulation.

OBJECTIVES: To determine the feasibility of preparing a long-term stable ready-to-use parenteral amiodarone formulation using cyclodextrins as dissolution enhancer. METHODS: A preformulation study was performed with different molar ratios of hydroxypropyl-beta-cyclodextrin (HP-BCD) or sulfobutylether-beta-cyclodextrin (SBE-BCD) to amiodarone in order to investigate enhancement of amiodarone's water solubility. Further, effects of pH and temperature on the dissolution rate during production were investigated. Shelf-life was determined for a ready-to-use iso-osmotic preparation of 1.8 mg/mL amiodarone with SBE-BCD in a molar ratio of 1:3. Amiodarone content was assessed using a validated high-pressure liquid chromatography ultraviolet method. RESULTS: Amiodarone-SBE-BCD in a molar ratio of 1:3 at pH 4.0-5.0 yielded the best results in terms of increased solubility and dissolution time (90 min). With SBE-BCD, a smaller molar ratio to amiodarone was needed than with HP-BCD. The amiodarone content of the final formulation stored 12 months at 21°C in daylight remained unchanged. CONCLUSIONS: A ready-to-use or ready-to-administer amiodarone product, prepared in a hospital pharmacy, for intravenous application in an acute clinical setting is a feasible option from a chemical, physical and microbiological point of view. The availability of such a product will have a significant impact on medication safety, and production should therefore be considered.

A levodopa dry powder inhaler for the treatment of Parkinson's disease patients in off periods.

Adequate treatment of Parkinson's patients in off periods with orally administered levodopa is hindered by a poor bioavailability and a slow onset of action. Hence, there is a need for a fast and reliable alternative as for instance via pulmonary administration of the drug. We developed a levodopa containing powder formulation for pulmonary delivery by a recently presented high dose dry powder inhaler (Cyclops). The objective was to produce the drug formulation by means of simple techniques such as micronization, either as pure active substance or with a minimum amount of excipients. After an initial screening on dispersion behaviour, the most promising formulation in the Cyclops was characterized in vitro over a range of pressure drops (2-6 kPa) and doses (20, 30 and 40 mg), representative of those to be expected in practice. A co-micronized levodopa formulation with 2% L-leucine appeared to yield the best aerosol properties for inhalation and highest delivered dose reproducibility. The combination of this particular formulation and the Cyclops inhaler seems to meet the basic requirements for satisfactory deposition in the airways. This formulation is therefore expected to be a promising candidate for the treatment of Parkinson's patients in an off period.