Can lipid nanoparticles improve intestinal absorption?
Lipid nanoparticles and their multiple designs have been considered appealing nanocarrier systems. Bringing the benefits of these nanosystems together with conventional coating technology clearly results in product differentiation. This work aimed at developing an innovative solid dosage form for oral administration based on tableting nanostructured lipid carriers (NLC), coated with conventional polymer agents. NLC dispersions co-encapsulating olanzapine and simvastatin (Combo-NLC) were produced by high pressure homogenization, and evaluated in terms of scalability, drying procedure, tableting and performance from in vitro release, cytotoxicity and intestinal permeability stand points. Factorial design indicated that the scaling-up of the NLC production is clearly feasible. Spray-drying was the method selected to obtain dry particles, not only because it consists of a single step procedure, but also because it facilitates the coating process of NLC with different polymers. Modified NLC formulations with the polymers allowed obtaining distinct release mechanisms, comprising immediate, delayed and prolonged release. Sureteric:Combo-NLC provided a low cytotoxicity profile, along with a ca. 12-fold OL/3-fold SV higher intestinal permeability, compared to those obtained with commercial tablets. Such findings can be ascribed to drug protection and control over release promoted by NLC, supporting them as a versatile platform able to be modified according to the intended needs.
Pharmacometrics Group of the Centre for Neurosciences and Cell Biology (CNC), University of Coimbra, 3004-517 Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
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M
Mendes
Department of Chemistry, University of Coimbra, Rua Larga, 3004-535 Coimbra, Portugal.
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HT
Soares
Department of Chemistry, University of Coimbra, Rua Larga, 3004-535 Coimbra, Portugal.
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LG
Arnaut
Pharmacometrics Group of the Centre for Neurosciences and Cell Biology (CNC), University of Coimbra, 3004-517 Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
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JJ
Sousa
Department of Chemistry, University of Coimbra, Rua Larga, 3004-535 Coimbra, Portugal.
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AACC
Pais
Pharmacometrics Group of the Centre for Neurosciences and Cell Biology (CNC), University of Coimbra, 3004-517 Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal. Electronic address: csvitorino@ff.uc.pt.
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C
Vitorino
D000284:Administration, Oral; D001569:Benzodiazepines / Q000737:chemistry / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003890:Desiccation / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D007408:Intestinal Absorption / Q000187:drug effects*; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D049329:Nanostructures / Q000737:chemistry; D000077152:Olanzapine; D010316:Particle Size; D010539:Permeability; D011108:Polymers / Q000737:chemistry; D019821:Simvastatin / Q000737:chemistry / Q000378:metabolism
D004337:Drug Carriers; D005079:Excipients; D008055:Lipids; D011108:Polymers; D001569:Benzodiazepines; D019821:Simvastatin; D000077152:Olanzapine
Co-encapsulation; Intestinal permeability; Nanostructured lipid carriers; Polymer coating; Scale-up; Spray-drying