A Traffic Light System to Maximize Carbohydrate Cryoprotectants’ Effectivity in Nanostructured Lipid Carriers’ Lyophilization
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. NLCs’ Formulation
2.2.2. NLCs’ Lyophilization and Reconstitution
2.2.3. Particle Size and Surface Charge Characterization
2.2.4. Osmolarity Determination
2.2.5. Modelling through Artificial Intelligence Tools
3. Results
3.1. Cryoprotectants’ Characterization
3.2. Physicochemical Characterization of NLCs and Lyophilized Powders
3.3. Influence of Lyophilization Variables over NLCs’ Characteristics (Model 1)
3.4. Influence of Cryoprotectant Properties and Operation Conditions over NLCs’ Characteristics (Model 2)
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AI | Artificial Intelligence |
ANN | Artificial Neural Networks |
CP/CPs | Cryoprotectant/Cryoprotectants |
LN | Lipid Nanoparticles |
LP | Lyophilized Powders |
MD | Membership Degree |
MW | Molecular Weight |
MWCP | CPs’ molecular weight |
NFL | Neurofuzzy Logic |
NLCs | Nanostructured Lipid Carriers |
PdI | Polydispersity Index |
SLN | Solid Lipid Nanoparticles |
Tg | Glass transition temperature |
Tg´ | Glass transition temperature of the maximum cryo-concentrated solution |
ZP | Zeta Potential |
Π | Osmolarity |
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CP | CP Concentration (%) | MwCP (g/mol) | Π (mmol/kg) |
---|---|---|---|
Fructose | 2.5 | 180.16 | 154 |
Fructose | 5 | 180.16 | 279 |
Fructose | 10 | 180.16 | 551 |
Fructose | 15 | 180.16 | 894 |
Fructose | 20 | 180.16 | 1141 |
Glucose | 2.5 | 180.16 | 135 |
Glucose | 5 | 180.16 | 257 |
Glucose | 10 | 180.16 | 547 |
Glucose | 15 | 180.16 | 820 |
Glucose | 20 | 180.16 | 1127 |
Mannitol | 2.5 | 182.17 | 142 |
Mannitol | 5 | 182.17 | 270 |
Mannitol | 10 | 182.17 | 593 |
Mannitol | 15 | 182.17 | 945 |
Sorbitol | 2.5 | 182.17 | 131 |
Sorbitol | 5 | 182.17 | 253 |
Sorbitol | 10 | 182.17 | 615 |
Sorbitol | 15 | 182.17 | 864 |
Sorbitol | 20 | 182.17 | 1146 |
Sucrose | 2.5 | 342.3 | 73 |
Sucrose | 5 | 342.3 | 140 |
Sucrose | 10 | 342.3 | 300 |
Sucrose | 15 | 342.3 | 434 |
Sucrose | 20 | 342.3 | 602 |
Trehalose | 2.5 | 342.3 | 70 |
Trehalose | 5 | 342.3 | 134 |
Trehalose | 10 | 342.3 | 281 |
Trehalose | 15 | 342.3 | 381 |
Trehalose | 20 | 342.3 | 538 |
Lactose | 2.5 | 342.3 | 72 |
Lactose | 5 | 342.3 | 142 |
Lactose | 10 | 342.3 | 248 |
Output | Submodels | Inputs from FormRules® | R2 | Calculated f Value | Degrees of Freedom | f Critical for p ˂ 0.01 |
---|---|---|---|---|---|---|
Δ size | Submodel 1 | CP × Speed | 91.77 | 10.17 | 34 and 31 | 2.32 |
Submodel 2 | CP × %CP | |||||
Δ PdI | Submodel 1 | CP × %CP | 76.04 | 8.29 | 18 and 47 | 2.34 |
Submodel 2 | Speed | |||||
Submodel 3 | %CP | |||||
Δ ZP | Submodel 1 | CP × Speed | 51.35 | 3.52 | 15 and 50 | 2.42 |
Submodel 2 | %CP |
Output | Submodels | Inputs from FormRules® | R2 | Calculated f Value | Degrees of Freedom | f Critical for p ˂ 0.01 |
---|---|---|---|---|---|---|
Δ size | Submodel 1 | MWCP × Π | 74.38 | 10.14 | 14 and 49 | 2.47 |
Submodel 2 | MWCP × Speed | |||||
Δ PdI | Submodel 1 | MWCP × Π | 70.50 | 12.65 | 10 and 53 | 2.68 |
Submodel 2 | Speed | |||||
Δ ZP | Submodel 1 | Π | 1.58 | 0.49 | 2 and 61 | 4.97 |
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Rouco, H.; Diaz-Rodriguez, P.; Guillin, A.; Remuñán-López, C.; Landin, M. A Traffic Light System to Maximize Carbohydrate Cryoprotectants’ Effectivity in Nanostructured Lipid Carriers’ Lyophilization. Pharmaceutics 2021, 13, 1330. https://doi.org/10.3390/pharmaceutics13091330
Rouco H, Diaz-Rodriguez P, Guillin A, Remuñán-López C, Landin M. A Traffic Light System to Maximize Carbohydrate Cryoprotectants’ Effectivity in Nanostructured Lipid Carriers’ Lyophilization. Pharmaceutics. 2021; 13(9):1330. https://doi.org/10.3390/pharmaceutics13091330
Chicago/Turabian StyleRouco, Helena, Patricia Diaz-Rodriguez, Alba Guillin, Carmen Remuñán-López, and Mariana Landin. 2021. "A Traffic Light System to Maximize Carbohydrate Cryoprotectants’ Effectivity in Nanostructured Lipid Carriers’ Lyophilization" Pharmaceutics 13, no. 9: 1330. https://doi.org/10.3390/pharmaceutics13091330
APA StyleRouco, H., Diaz-Rodriguez, P., Guillin, A., Remuñán-López, C., & Landin, M. (2021). A Traffic Light System to Maximize Carbohydrate Cryoprotectants’ Effectivity in Nanostructured Lipid Carriers’ Lyophilization. Pharmaceutics, 13(9), 1330. https://doi.org/10.3390/pharmaceutics13091330