title: Continuous and sustainable granulation of nanopharmaceuticals by spray coagulation encapsulation in alginate.
abstract: Nanopharmaceuticals (NPs) have emerged as an attractive formulation strategy for bioavailability enhancement of poorly soluble drugs. Their oral solid dosage form preparation requires them to undergo granulation before they can be processed into tablets. Existing NP granulation methods (e.g., spray drying, spray granulation), however, are lacking in sustainability due to their high energy expense and low mass efficiency. Herein we developed a one-step continuous NP granulation process via encapsulation by spray coagulation (ESC) in alginate, which transforms the NP immediately upon their preparation, thus removing the need for NP recovery prior to granulation, resulting in a highly sustainable process. Moreover, unlike spray-dried NP granules, the ESC-prepared granules are readily compacted into tablets owed to their larger size, thus further enhancing the overall sustainability of the solid dosage form preparation. Crystalline fenofibrate nanoparticles prepared by confined impinging jet crystallization were used as the model NP. Granules containing 25% NPs by mass with size ≈ 300 ± 100 μm were successfully prepared at >80% yield. The NPs maintain their fast dissolution (relative to native microcrystalline fenofibrate) after granulation. The tableted NP granules, having uniform dosage, exhibit similar drug release profiles as the free granules indicating complete granule disassociation from the tablets.
authors.affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University, 637459, Singapore.
authors.forename: Kunn
authors.initials: K
authors.lastname: Hadinoto
authors.affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University, 637459, Singapore. Electronic address: kunnong@ntu.edu.sg.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000327:Adsorption; D000464:Alginates / Q000737:chemistry*; D065546:Drug Liberation; D011345:Fenofibrate / Q000737:chemistry*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D012967:Sodium Dodecyl Sulfate; D020723:Glucuronic Acid; D011345:Fenofibrate
keywords: Continuous pharmaceutical processing; Fenofibrate; Granules; Impinging jet crystallization; Nanomedicine