1. Design & Characterization of Nanocrystals of Lovastatin for Solubility & Dissolution Enhancement
Dr. Basavaraj K. Nanjwade M. Pharm, PhD.
Department of Pharmaceutics
KLE University’s College of Pharmacy
Belgaum
Cell No:

2. Introduction Nanocrystal Definition:
Drug nanocrystals are nanoparticles being composed of 100% drug without any matrix material.
Methods of production:
- Bottom up technology:
Precipitation
- Top down technology:
High pressure homogenization
08/02/2010
NIPER, Chandigarh

3. Objectives of the study:
To increase the drug solubility & dissolution.
To increase the drug bioavailability.
Materials & Methods:
Materials:
Drug: Lovastatin (Kreb’s biochemicals Pvt. Ltd., Hyderabad)
Solvents: Acetone, Methanol, Acetonitrile
08/02/2010
NIPER, Chandigarh

4. All the formulations were prepared by Precipitation method.
Involves two steps…..
Preparation of drug solution in solvent
Addition of drug solution to water
08/02/2010
NIPER, Chandigarh

5. Nanocrystal preparation
Sr. no.
Code
Organic solvent
LVS Concentration in solvent
(mM)
Dilution of LVS solution to water
Volume of LVS solution
(ml)
Volume of water 1. 2. 3. 4. 5. 6.
F1A
F1B
Acetone
3 mM
4 mM
12.3 ml
10.8 ml
615 ml
540 ml
F2A
F2B
Methanol
F3A
F3B
Acetonitrile
08/02/2010
NIPER, Chandigarh

6. Evaluation parameters
a) Particle morphology
b) Particle size analysis
c) Crystalline state evaluation
- Powder X-ray diffraction (PXRD)
- Differential scanning calorimetry (DSC)
d) Solubility determination
e) In vitro release study
f) In vivo evaluation
g) Stability study
08/02/2010
NIPER, Chandigarh

7. Result & discussion a) Particle Morphology
F1A
Pure LVS
F2A
08/02/2010
NIPER, Chandigarh

8. b) Particle size analysis
08/02/2010
NIPER, Chandigarh

9. c) Crystalline state evaluation
Powder X-Ray diffraction (PXRD): A A A
08/02/2010
NIPER, Chandigarh

10. Differential scanning calorimetry (DSC):
Endothermic peak: ˚C A
Endothermic peak: ˚C A
Endothermic peak: ˚C
Endothermic peak: ˚C
08/02/2010
NIPER, Chandigarh

11. d) Solubility determination
Sr. No
Media
used
Solubility in each media (mg/ml)
Average ± SD
Pure LVS
F1A
F1B
F2A
F2B
F3A
F3B 1.
Distilled
water
0.005
0.01
0.092
0.02
0.089
0.03
0.090
0.05
0.084
0.081
0.076 2.
Acidic
buffer
PH 1.2
0.007
0.148
0.04
0.136
0.131
0.129
0.097 3.
Phosphate
buffer PH 7.4
0.008
0.176
0.161
0.173
0.154
0.134
0.105
08/02/2010
NIPER, Chandigarh

12. e) In- vitro release studies
08/02/2010
NIPER, Chandigarh

13. f) In- vivo evaluation In vivo drug release of pure LVS
In vivo drug release of F1A and F2A nanocrystals
08/02/2010
NIPER, Chandigarh

14. Comparison of Bioavailability of LVS nanocrystals
Code
Absolute bioavailability
Relative bioavailability
Area under curve(0-8) (µg/ml.hrs)
Cmax (µg/ml)
Tmax (hrs.)
Oral control group
802.8
5.849± 0.245 2
IV control group
986.7
9.546± 0.094 5*
F1A
0.826
1.015
815.3
6.325± 0.324
F2A
0.821
1.010
810.9
5.590± 0.432
* Time in minute
Values of Cmax are mean ± standard deviation
08/02/2010
NIPER, Chandigarh

15. g) Stability study F1A 66.46% 66.32% 60.54%
Drug content after 30 days storage of F1A
Code
Percent drug content at 40C
Percent drug content at 300C±20C / 65%± 5% RH
Percent drug content at 400C±20C/ 65%± 5% RH
F1A
66.46%
66.32%
60.54%
08/02/2010
NIPER, Chandigarh

16. Continued…..
Release study of F1A stored at 40C, at 300C±20C / 65%± 5% RH and
at 400C±20C/ 65%± 5% RH
Time
(Min.)
% Cumulative LVS release stored at 40C
% Cumulative LVS release stored at 300C±20C / 65%± 5% RH
% Cumulative LVS release stored at 400C±20C/ 65%± 5% RH 15
44.96
45.23
41.03 30
59.16
59.63
54.24 45
70.20
70.86
65.03 60
75.03
75.53
71.26 90
82.97
83.18
79.06
120
87.06
87.45
82.36
150
90.31
90.35
88.65
180
93.76
93.06
89.30
08/02/2010
NIPER, Chandigarh

17. Conclusion
From the particle morphology by SEM, it was observed that LVS nanocrystals remain crystalline.
Less particle size was observed in case of F1A & F2A as compared to all other.
From PXRD and DSC data, it was observed that F1A , F2A & F3A showed no significant change in crystalline as compared to pure LVS.
Solubility was enhanced due to less particle size & solvent used (acetone & methanol).
08/02/2010
NIPER, Chandigarh

18. Conclusion
In-vitro release rate studies showed that the maximum drug release was found in the F1A & F2A in the required period of time.
In-vivo relative bioavailability of F1A & F2A was slightly increased as compared to absolute bioavailability.
From stability study data it was revealed that nanocrystals of lovastatin remained more stable at 4ºC. The maximum instability of nanocrystals was observed at 402C.
08/02/2010
NIPER, Chandigarh

19. E-mail: bknanjwade@yahoo.co.in
THANK YOU
THANK YOU….
08/02/2010
NIPER, Chandigarh
Cell No: