Design and evaluation of sustained release spherical agglomerates of Fluvastatin sodium by crystallo-co-agglomeration

Abstract

Prime objective of present study was to design and evaluate ready to compress sustained release spherical agglomerates of Fluvastatin sodium. Crystallo-co-agglomeration technique of spherical crystallization utilizing acetone-acetonitrile system was used to prepare spherical agglomerates of drug in presence of Eudragit RS100 and RL100 as release retardant polymers. Prepared agglomerates were subjected for evaluation of flow, packing, mechanical, compaction properties as well as in-vitro dissolution study. Morphology of spherical agglomerates was evaluated by SEM and drug-polymer compatibility was carried out by DSC, FTIR and XRD. Matrix beads were generated having uniform dispersion of drug with enhanced flow, packing, compaction and mechanical properties which can be attributed to spherical shape of agglomerates as revealed in SEM photomicrographs. Higher crushing strength of agglomerates was indication of good mechanical strength. Improved compressibility of agglomerates was indicated by lower values of σ0, improved tensile strength and reduced elastic recovery. DSC, FTIR and XRD showed that drug did not undergo structural or polymorphic alterations in presence of polymers. In-vitro dissolution study suggested utilization of process for sustained release of fluvastatin sodium for sufficiently prolonged period of time depending on polymer concentration. Thus, crystallo-co-agglomeration method can be successfully utilized for development of directly compressible sustained release agglomerates.

Improved flowability, mechanical and dissolution properties of metronidazole obtained from crystallo coagglomeration technique for direct tableting

“…The mean particle diameter of agglomerates was found to be 3-times greater than that of pure drug crystals, suggesting particle growth by simultaneous agglomeration following crystallization. This may be due to enhanced bonding and bridging in the presence of polymers, a finding that aligns with research of Shah and Sorathia on the evaluation of spherical agglomerates of Fluvastatin [16].…”

Crystallo-co-Agglomeration Technique for Improving Physicochemical Properties, Compressibility and Solubility Characteristics of Metronidazole

“…The findings indicated 4-folds rise in mean particle diameter of agglomerates compared to pure drug crystals which indicated growth of particles by simultaneous agglomeration after crystallization due to enhanced bonding and bridging formed in presence of polymers. This is in line with studies conducted by Shah and Sorathia on evaluation of spherical agglomerates of Fluvastatin (Shah and Sorathia, 2017). From the particle size analysis of the co-agglomerates, the predominant particle size was 500 μm followed by 90, 250, 150, 75 and 45 μm.…”

Particle Design of Drugs via Spherical Crystallization: A Review from Fundamental Aspects to Technology Development

“…135 It was discovered that the excipients not only can act as a dispersing carrier to improve the solubility and dissolution rate of the poorly insoluble drugs such as cilostazol, 132 bicalutamide, 140 and glimepiride 136 but also can serve as a retarding agent to control the release rate of the drugs including carbamazepine, 121 ketoprofen, 123 ibuprofen, 124 theophylline, 141 and fluvastatin sodium. 131 For a complex CCA process, the rational design of experiments and drug particles is important. Raval attributes.…”

“…The effects of excipients on the particle properties were also explored for the CCA processes of secnidazole, bicalutamide, indapamide, and indomethacin–saccharin co-crystals . It was discovered that the excipients not only can act as a dispersing carrier to improve the solubility and dissolution rate of the poorly insoluble drugs such as cilostazol, bicalutamide, and glimepiride but also can serve as a retarding agent to control the release rate of the drugs including carbamazepine, ketoprofen, ibuprofen, theophylline, and fluvastatin sodium …”