Design

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• Design Characterization of Nanocrystals of
  Lovastatin for Solubility Dissolution
  Enhancement

Dr. Basavaraj K. Nanjwade M. Pharm,
PhD. Department of Pharmaceutics KLE Universitys
College of Pharmacy Belgaum-590010 E-mail
bknanjwade_at_yahoo.co.in Cell No 00919742431000
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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

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• Objectives of the study
• To increase the drug solubility dissolution.
• To increase the drug bioavailability.
• Materials Methods
• Materials
• Drug Lovastatin (Krebs biochemicals Pvt. Ltd.,
  Hyderabad)
• Solvents Acetone, Methanol, Acetonitrile

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• Method
• All the formulations were prepared by
  Precipitation method.
• Involves two steps..
• Preparation of drug solution in solvent
• Addition of drug solution to water

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

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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

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Result discussion a) Particle Morphology
F1A
Pure LVS
F2A
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b) Particle size analysis
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c) Crystalline state evaluation
Powder X-Ray diffraction (PXRD)
A
A
A
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• Differential scanning calorimetry (DSC)

A
Endothermic peak 174.57C
A
Endothermic peak 174.87C
A
Endothermic peak 173.92C
Endothermic peak 175.19C
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d) Solubility determination
Sr. No Media used Solubility in each media (mg/ml) Average SD Solubility in each media (mg/ml) Average SD Solubility in each media (mg/ml) Average SD Solubility in each media (mg/ml) Average SD Solubility in each media (mg/ml) Average SD Solubility in each media (mg/ml) Average SD Solubility in each media (mg/ml) Average SD
Sr. No Media used 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 0.02 0.081 0.01 0.076 0.02
2. Acidic buffer PH 1.2 0.007 0.03 0.148 0.04 0.136 0.02 0.131 0.03 0.129 0.04 0.097 0.03 0.089 0.04
3. Phosphate buffer PH 7.4 0.008 0.02 0.176 0.01 0.161 0.04 0.173 0.01 0.154 0.03 0.134 0.04 0.105 0.01
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e) In- vitro release studies
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• f) In- vivo evaluation
• In vivo drug release of pure LVS

In vivo drug release of F1A and F2A nanocrystals
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• 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 2
F2A 0.821 1.010 810.9 5.590 0.432 2
Time in minute Values of Cmax are mean
standard deviation
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g) Stability study

• Drug content after 30 days storage of F1A

Code Percent drug content at 40C Percent drug content at 300C20C / 65 5 RH Percent drug content at 400C20C/ 65 5 RH
F1A 66.46 66.32 60.54
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• 
  Continued..

• Release study of F1A stored at 40C, at 300C20C
  / 65 5 RH and
• at 400C20C/ 65 5 RH

Time (Min.) Cumulative LVS release stored at 40C Cumulative LVS release stored at 300C20C / 65 5 RH Cumulative LVS release stored at 400C20C/ 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
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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).

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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.

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THANK YOU

• THANK YOU.

E-mail bknanjwade_at_yahoo.co.in Cell No
0091974243100