Role of Polymeric Excipients in the Stabilization of Olanzapine when Exposed to Aqueous Environments
Abstract
:1. Introduction
2. Results
2.1. Polymer Screening Method to Identify Polymers that can Stabilize OLZ FI during Wet Massing
γd 1 (mN/m) | γp 1 (mN/m) | γ 1 (mN/m) | Polarity (%) | Wc 2 (mJ/m2) | Wa 2 (mJ/m2) | Wa−Wc 3 (mJ/m2) | |
---|---|---|---|---|---|---|---|
OLZ | 41.31 | 1.19 | 42.50 | 3 | 85.00 | ||
PEG 6000 | 35.71 | 14.62 | 50.33 | 29 | 100.66 | 81.01 | −19.65 |
PEG 40,000 | 34.78 | 12.93 | 47.71 | 27 | 95.42 | 79.89 | −15.53 |
PVP k12 | 43.22 | 7.48 | 50.71 | 15 | 101.42 | 88.59 | −12.83 |
PVP k30 | 40.46 | 6.73 | 47.19 | 14 | 94.38 | 85.81 | −8.57 |
HPC LF | 31.90 | 4.80 | 36.70 | 13 | 73.40 | 75.81 | 2.41 |
Raw-Material | Contact Angle (θ/°) | Formulations after Massing | Contact angle (θ/°) |
---|---|---|---|
OLZ | 104.65 ± 0.64 | A | 104.87 ± 0.74 |
PEG 6000 | 63.60 ± 2.05 | B1 | 81.24 ± 2.98 |
PEG 40,000 | 64.30 ± 1.95 | B2 | 79.52 ± 1.07 |
HPC-LF | 91.84 ± 0.47 | C | 87.41 ± 1.72 |
PVP k12 | 56.46 ± 1.36 | D1 | 79.73 ± 1.54 |
PVP K30 | 75.77 ± 2.17 | D2 | 89.14 ± 3.40 |
2.2. Characterization of OLZ Wet Masses and Pellets Containing Microcrystalline Cellulose
Formulation | First-Order Model | Higuchi Model | Korsmeyer-Peppas Model | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Adj R2 | MSE Root | K1 | Adj R2 | MSE Root | kH | Adj R2 | MSE Root | kKP | n | ||
AM | #1 | 0.669 | 9.946 | 0.001 | 0.952 | 3.797 | 1.648 | 0.997 | 0.958 | 3.585 | 0.383 |
#2 | 0.706 | 8.624 | 0.001 | 0.97 | 2.728 | 1.441 | 0.995 | 1.127 | 2.676 | 0.407 | |
B1M | #1 | 0.82 | 10.15 | 0.002 | 0.962 | 4.674 | 2.218 | 0.994 | 1.794 | 4.442 | 0.395 |
#2 | 0.839 | 8.466 | 0.001 | 0.986 | 2.464 | 1.821 | 0.995 | 1.554 | 2.703 | 0.441 | |
CM | #1 | 0.951 | 6.910 | 0.002 | 0.986 | 3.81 | 2.696 | 0.995 | 2.226 | 4.450 | 0.431 |
#2 | 0.926 | 8.408 | 0.003 | 0.973 | 5.044 | 2.755 | 0.995 | 2.353 | 4.966 | 0.411 | |
DM | #1 | 0.972 | 5.697 | 0.003 | 0.958 | 6.991 | 2.995 | 0.980 | 4.801 | 5.510 | 0.408 |
#2 | 0.978 | 5.115 | 0.003 | 0.956 | 7.321 | 3.069 | 0.981 | 4.658 | 5.494 | 0.410 |
3. Discussion
4. Experimental Section
4.1. Materials
4.1.1. OLZ Dihydrate B
4.1.2. OLZ Dihydrate E
4.1.3. OLZ Higher Hydrate
4.2. Methods
4.2.1. Conversion of OLZ FI during Wet Massing in the Presence of Polymers
4.2.2. Manufacture of Pellets Containing Polymers
Formulation | Components (in Parts) | ||
---|---|---|---|
OLZ | Polymer | MCC | |
AM | 1.5 | - | 8.5 |
B1M | 1.5 | 1.0 (PEG 6000) | 7.5 |
B2M | 1.5 | 1.0 (PEG 40,000) | 7.5 |
CM | 1.5 | 1.0 (HPC-LF) | 7.5 |
D1M | 1.5 | 1.0 (PVP k12) | 7.5 |
D2M | 1.5 | 1.0 (PVP k30) | 7.5 |
4.2.3. Characterization of Blends and Pellets
X-ray Powder Diffraction (XRPD)
Differential Scanning Calorimetry (DSC)
FT-Infrared Spectroscopy (FTIR)
Scanning Electron Microscopy (SEM)
Wettability and Surface Energy Measurements
Dissolution Studies
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
API | Active pharmaceutical ingredient |
CSD | Cambridge structural database |
DSC | dynamic scanning calorimetry |
Formulation A (A) | OLZ + water |
Formulation B1/B2 (B1/B2) | OLZ + (PEG 6000/PEG 40,000) + water |
Formulation C (C) | OLZ + HPC + water |
Formulation D1/D2 (D1/D2) | OLZ + (PVP k12/PVP k30) + water |
Formulation AM (A) | OLZ + water + MCC |
Formulation B1M/B2M (B1M/B2M) | OLZ + (PEG 6000/PEG 40,000) + water + MCC |
Formulation CM (CM) | OLZ + HPC + water + MCC |
Formulation D1M/D2M (D1M/D2M) | OLZ + (PVP k12/PVP k30) + water + MCC |
FTIR | Fourier transformed infrared spectroscopy |
HPC | Hydroxypropylcellulose |
HPMC | Hydroxypropylmethylcellulose |
MCC | Microcrystalline cellulose |
OLZ | Olanzapine |
PVP | Polyvinylpyrrolidone |
SEM | Scanning electronic microscopy |
SMT | Solvent-mediated polymorphic transformations |
XRPD | X-ray powder diffraction |
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Paisana, M.; Wahl, M.; Pinto, J. Role of Polymeric Excipients in the Stabilization of Olanzapine when Exposed to Aqueous Environments. Molecules 2015, 20, 22364-22382. https://doi.org/10.3390/molecules201219832
Paisana M, Wahl M, Pinto J. Role of Polymeric Excipients in the Stabilization of Olanzapine when Exposed to Aqueous Environments. Molecules. 2015; 20(12):22364-22382. https://doi.org/10.3390/molecules201219832
Chicago/Turabian StylePaisana, Maria, Martin Wahl, and João Pinto. 2015. "Role of Polymeric Excipients in the Stabilization of Olanzapine when Exposed to Aqueous Environments" Molecules 20, no. 12: 22364-22382. https://doi.org/10.3390/molecules201219832