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-590010 E-mail: bknanjwade@yahoo.co.in Cell No: 00919742431000
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
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
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
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
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
Result & discussion a) Particle Morphology F1A Pure LVS F2A 08/02/2010 NIPER, Chandigarh
b) Particle size analysis 08/02/2010 NIPER, Chandigarh
c) Crystalline state evaluation Powder X-Ray diffraction (PXRD): A A A 08/02/2010 NIPER, Chandigarh
Differential scanning calorimetry (DSC): Endothermic peak: 174.57˚C A Endothermic peak: 174.87˚C A Endothermic peak: 173.92˚C Endothermic peak: 175.19˚C 08/02/2010 NIPER, Chandigarh
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
e) In- vitro release studies 08/02/2010 NIPER, Chandigarh
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
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
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
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
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
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 402C. 08/02/2010 NIPER, Chandigarh
E-mail: bknanjwade@yahoo.co.in THANK YOU THANK YOU…. 08/02/2010 NIPER, Chandigarh E-mail: bknanjwade@yahoo.co.in Cell No: 0091974243100