Development of a Versatile Lipid Core for Nanostructured Lipid Carriers (NLCs) Using Design of Experiments (DoE) and Raman Mapping
Abstract
:1. Introduction
2. Materials and Methods
2.1. Excipients
2.2. Solubility Tests
2.3. Tablet Preparation
2.4. Raman Spectra
2.5. Chemical Maps
2.6. Design of Experiments (DoE)
2.7. Evaluation of the Optimized Mixture Profile Using Different Drugs
3. Results and Discussion
3.1. Solubility Tests
3.2. Chemical Maps of Binary Mixtures
- The excipients that exhibited a hydrophobic profile (Super Refined™ Sesame Oil, Super Refined™ Oleic Acid, Super Refined™ Soybean Oil, and Super Refined™ GTCC) were miscible in all evaluated proportions with CrodamolTM CP pharma.
- The hydrophilic excipients, Super Refined™ Propylene Glycol and Super Refined™ PEG 400, were not miscible with CrodamolTM CP pharma (it was not possible to obtain a tablet in any proportion tested).
- Crodasol™ HS HP and Croduret™ 40 allowed the preparation of a tablet; however, chemical imaging revealed that the excipients were localized in different phases (upper/lower sides of the tablets).
- The excipient Super Refined™ DMI was the only hydrophilic excipient that formed a tablet; nevertheless, the histogram demonstrated a broad distribution of concentrations.
- Within the group of excipients classified as medium polarity, all excipients provided suitable miscibility with Crodamol™ CP pharma, with slight minor variations at different concentrations. The best overall proportion was 1:1 (Gaussian profile) in all cases.
3.3. Development of an Optimized Mixture
3.3.1. Response Y1: STD Crodamol™ CP Pharma
3.3.2. Response Y2: STD Super Refined™ DMI
3.3.3. Response Y3: STD Super Refined™ Lauryl Lactate, Y3
3.4. Surface and Contour Graphs
3.5. Incorporation of Different Drugs into the Lipid Core
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Correction Statement
References
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Independent Variables | Range (% w/w) | |
---|---|---|
Minimum | Maximum | |
X1: Lipid solid (Crodamol™ CP pharma) | 40 | 70 |
X2: Hydrophilic excipient (Super Refined™ DMI) | 10 | 40 |
X3: Liquid lipid (Super Refined™ Lauryl Lactate) | 10 | 40 |
Dependent variables: CLS standard deviation | Target | |
Y1: STD Crodamol™ CP pharma | Minimize | |
Y2: STD Super Refined™ DMI | Minimize | |
Y3: STD Super Refined™ Lauryl Lactate | Minimize |
Independent Variables | |||
---|---|---|---|
Mixture | Crodamol™ CP Pharma (X1, % w/w) | Super Refined™ DMI (X2, % w/w) | Super Refined™ Lauryl Lactate (X3, % w/w) |
1 | 70 | 10 | 10 |
2 | 40 | 40 | 10 |
3 | 40 | 10 | 40 |
4 | 55 | 25 | 10 |
5 | 55 | 10 | 25 |
6 | 40 | 25 | 25 |
7 | 60 | 15 | 15 |
8 | 45 | 30 | 15 |
9 | 45 | 15 | 30 |
10 | 50 | 20 | 20 |
11 | 70 | 10 | 10 |
12 | 40 | 40 | 10 |
13 | 40 | 10 | 40 |
14 | 50 | 20 | 20 |
15 | 50 | 20 | 20 |
Independent Variables | Dependent Variables (Responses) | ||||||
---|---|---|---|---|---|---|---|
Point | Ord. | Crodamol™ CP Pharma (X1, % w/w) | Super Refined™ DMI (X2, % w/w) | Super Refined™ Lauryl Lactate (X3, % w/w) | STD Crodamol™ CP Pharma (Y1) | STD Super Refined™ DMI (Y2) | STD Super Refined™ Lauryl Lactate (Y3) |
A (REP. 1) | 3 | 70 | 10 | 10 | 10.2399 | 5.3213 | 6.2387 |
B (REP. 1) | 15 | 40 | 40 | 10 | 9.7734 | 10.2075 | 3.6419 |
C (REP. 1) | 10 | 40 | 10 | 40 | 8.2503 | 2.8535 | 8.3707 |
D | 14 | 55 | 25 | 10 | 8.6425 | 9.049 | 4.5951 |
E | 8 | 55 | 10 | 25 | 6.4922 | 2.9182 | 6.7683 |
F | 2 | 40 | 25 | 25 | 10.2123 | 6.7501 | 6.8751 |
G | 6 | 60 | 15 | 15 | 7.6515 | 5.106 | 5.3594 |
H | 11 | 45 | 30 | 15 | 9.8017 | 9.3369 | 5.3381 |
I | 1 | 45 | 15 | 30 | 5.5927 | 4.5703 | 5.6872 |
J (REP. 1) | 5 | 50 | 20 | 20 | 5.2051 | 5.1883 | 3.6223 |
A (REP. 2) | 4 | 70 | 10 | 10 | 5.4646 | 3.5034 | 4.4966 |
B (REP. 2) | 7 | 40 | 40 | 10 | 5.8229 | 9.6252 | 2.1367 |
C (REP. 2) | 9 | 40 | 10 | 40 | 6.9807 | 3.791 | 7.9058 |
J (REP. 2) | 12 | 50 | 20 | 20 | 7.209 | 6.3858 | 4.6373 |
J (REP. 3) | 13 | 50 | 20 | 20 | 7.4431 | 7.9701 | 5.6311 |
Response | Model | Sequential p-Value | SD | R2 | Adjusted R2 | Predicted R2 | |
---|---|---|---|---|---|---|---|
Y1 | Mean | <0.0001 | |||||
Y2 | Linear | <0.0001 | 0.988 | 0.870 | 0.848 | 0.799 | |
Y3 | Linear | 0.000518 | 0.959 | 0.717 | 0.669 | 0.567 | |
Response | Source | Sum of Squares | df | Mean square | F-value | p-value, prob > F | Conclusion |
Y1 | Model | 0 | 0 | ||||
Residual | 44.1 | 14 | 3.15 | ||||
Lack of Fit | 21.1 | 9 | 2.34 | 0.508 | 0.822 | Not significant | |
Pure Error | 23 | 5 | 4.61 | ||||
Corrected Total | 44.1 | 14 | |||||
Y2 | Model | 78.2 | 2 | 39.1 | 40.1 | <0.0001 | Significant |
Residual | 11.7 | 12 | 0.975 | ||||
Lack of Fit | 5.55 | 7 | 0.793 | 0.644 | 0.712 | Not significant | |
Pure Error | 6.16 | 5 | 1.23 | ||||
Corrected Total | 89.9 | 14 | |||||
Y3 | Model | 27.9 | 2 | 14 | 15.2 | 0.000518 | Significant |
Residual | 11 | 12 | 0.919 | ||||
Lack of Fit | 6.26 | 7 | 0.894 | 0.936 | 0.549 | Not significant | |
Pure Error | 4.78 | 5 | 0.955 | ||||
Corrected Total | 38.9 | 14 |
STD | Lower | Upper | Criteria |
---|---|---|---|
Y1 | 5.2051 | 10.2399 | None |
Y2 | 2.8535 | 10.2075 | Minimize |
Y3 | 2.1367 | 8.3707 | Minimize |
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Rios, C.A.; Ondei, R.; Breitkreitz, M.C. Development of a Versatile Lipid Core for Nanostructured Lipid Carriers (NLCs) Using Design of Experiments (DoE) and Raman Mapping. Pharmaceutics 2024, 16, 250. https://doi.org/10.3390/pharmaceutics16020250
Rios CA, Ondei R, Breitkreitz MC. Development of a Versatile Lipid Core for Nanostructured Lipid Carriers (NLCs) Using Design of Experiments (DoE) and Raman Mapping. Pharmaceutics. 2024; 16(2):250. https://doi.org/10.3390/pharmaceutics16020250
Chicago/Turabian StyleRios, Carlos Alberto, Roberta Ondei, and Márcia Cristina Breitkreitz. 2024. "Development of a Versatile Lipid Core for Nanostructured Lipid Carriers (NLCs) Using Design of Experiments (DoE) and Raman Mapping" Pharmaceutics 16, no. 2: 250. https://doi.org/10.3390/pharmaceutics16020250
APA StyleRios, C. A., Ondei, R., & Breitkreitz, M. C. (2024). Development of a Versatile Lipid Core for Nanostructured Lipid Carriers (NLCs) Using Design of Experiments (DoE) and Raman Mapping. Pharmaceutics, 16(2), 250. https://doi.org/10.3390/pharmaceutics16020250