Spray-Dried Microspheres of Carboplatin: Technology to Develop Longer-Acting Injectable with Improved Physio-Chemical Stability, Toxicity, and Therapeutics.
Shubham ThakurRasdeep KourSatwinderjeet KaurSubheet Kumar JainPublished in: AAPS PharmSciTech (2022)
The present study aims to develop carboplatin injectable microspheres using spray-drying technology. The optimized powdered microspheres (MS-19-ST2) were morphologically spherical, with a 1.795 μm particle size and good micromeritic properties. Under normal temperature conditions, the MS-19-ST2 formulation exhibited a sustained release behaviour following first-order drug release kinetics with no compatibility issues with aluminium syringes. Furthermore, MS-19-ST2 formulation outperformed its commercial counterpart in terms of in vivo pharmaco-kinetics and -dynamics (MRT-13.9 ± 0.9 h, T 1/2 -8.2 ± 0.3 h, tumour inhibition-74.5%). Additionally, the MS-19-ST2 formulation was much safer to use than its commercial counterpart, as observed from the results of ex vivo (haemolytic, MTT, and cell apoptosis assays) and in vivo (14-day acute and 28-day sub-acute) toxicity studies. The above results confirm the MS-19-ST2 formulation as a good candidate to commercialize carboplatin in a powdered microsphere form (stable for 24 h after reconstitution) with improved pharmacokinetics, therapeutic, and toxicity profile.
Keyphrases
- mass spectrometry
- drug delivery
- multiple sclerosis
- ms ms
- drug release
- liver failure
- oxidative stress
- respiratory failure
- drug induced
- cell proliferation
- liquid chromatography
- squamous cell carcinoma
- randomized controlled trial
- hyaluronic acid
- aortic dissection
- phase iii
- high throughput
- intensive care unit
- radiation therapy
- open label
- extracorporeal membrane oxygenation
- simultaneous determination