Modulation of the clinically accessible gelation time using glucono-d-lactone and pyridoxal 5′-phosphate for long-acting alginate in situ forming gel injectable. (15th November 2021)

• Record Type: Journal Article
• Authors: Kim, Hyungtaek; Song, Dahee; Ngo, Hai V.; Jin, Gang; Park, Chulhun; Park, Jun-Bom; Lee, Beom-Jin
• Is Part Of: Carbohydrate polymers. Volume 272(2021)
• Publication Date: 2021-11-15
• Subjects: ASM Alginate solution mixture -- ISFG In-situ forming gel -- PLP Pyridoxal 5′-phosphate -- PPP Paliperidone palmitate -- GDL Glucono-d-lactone -- LAI Long-acting injectable -- FT-IR Fourier transform infrared spectroscopy -- PXRD Powder X-ray diffraction -- DSC Differential scanning calorimetry -- PLGA Poly(lactic-co-glycolic acid) -- ISFI In situ forming implant -- PBS Phosphate-buffered saline -- SR Swelling ratio -- DR Degradation ratio -- G Gauge; Paliperidone palmitate -- In situ forming gel -- Clinically acceptable gelation time -- Pyridoxal 5′-phosphate -- Glucono-d-lactone -- Particle-size reduction -- Controlled release; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2021.118453
• Languages: English
• ISSNs: 0144-8617

Abstract

Abstract: The purpose of this study was to design alginate in situ forming gel (ISFG) injectable with clinically acceptable gelation time and controlled release of hydrophobic drug. Milled or unmilled paliperidone palmitate (PPP) was used. The gelation time was controlled by varying the ratios of glucono-d-lactone (GDL) and pyridoxal 5′-phosphate (PLP) in prefilled alginate solution mixtures (ASMs) containing PPP, CaCO3, GDL and PLP for clinically acceptable injectability. However, the gelation time was varied by the alginate type (M/G ratio), storage condition, and drug solubilizers. This ISFG exhibited 32.15 kPa of the maximal compressive stress without causing pain and stiffness. The ISFG containing conically milled PPP released PPP in a controlled manner without exhibiting any initial burst release for 4 weeks. The current alginate ISFG injectable using new combination of PLP and GDL could be used to deliver long-acting injectable drugs. Graphical abstract: Unlabelled Image Highlights: The gelation time of alginate ISFG was efficiently modulated by varying ratio of GDL and PLP, alginate type, storage condition, particle size of drug and drug solubilizers. Injectability could be improved by reducing the particle size of the drug in the prefilled ASMs. The conically milled PPP-loaded alginate ISFG exhibited good injectability and controlled release of PPP for 4 weeks.