Formulation Development and <i>In-Vivo</i> Evaluation of Atorvastatin Calcium Solid Dispersion in Streptozotocin Induced Diabetic Mice — Oak Academic Publishing
Research ArticleOpen AccessGoogle Scholar indexed
Formulation Development and <i>In-Vivo</i> Evaluation of Atorvastatin Calcium Solid Dispersion in Streptozotocin Induced Diabetic Mice
Department of Pharmacy, Faculty of Science, University of Rajshahi, Rajshahi, Bangladesh
,
Department of Pharmacy, Faculty of Science, University of Rajshahi, Rajshahi, Bangladesh
,
Department of Pharmacy, Mawlana Bhasani University of Science of Technology, Tangail, Bangladesh
,
Laboratory of Pharmaceutics, Faculty of Pharmaceutical Sciences, Toho University, Chiba, Japan
,
Department of Pharmaceutical Engineering and Drug Delivery Science, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
,
Department of Pharmaceutical Engineering and Drug Delivery Science, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
,
Department of Pharmacy, Faculty of Science, University of Rajshahi, Rajshahi, Bangladesh
1 Department of Pharmacy, Faculty of Science, University of Rajshahi, Rajshahi, Bangladesh
2 Department of Pharmacy, Faculty of Science, University of Rajshahi, Rajshahi, Bangladesh
3 Department of Pharmacy, Mawlana Bhasani University of Science of Technology, Tangail, Bangladesh
4 Laboratory of Pharmaceutics, Faculty of Pharmaceutical Sciences, Toho University, Chiba, Japan
5 Department of Pharmaceutical Engineering and Drug Delivery Science, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
6 Department of Pharmaceutical Engineering and Drug Delivery Science, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
7 Department of Pharmacy, Faculty of Science, University of Rajshahi, Rajshahi, Bangladesh
Atorvastatin calcium ( ATV) is a selective competitive inhibitor of HMG CoA reductase characterized by poor aqueous solubility leading to inadequate bioavailability. The present study was designed to develop solid dispersion of atorvastatin (SDA) to improve the solubility and dissolution properties of ATV and evaluation of its in-vivo efficiency in s treptozotocin (STZ) induced diabetic mice. Formulations of SDA were prepared by solvent evaporation method using PEG-4000 alone and/or mixture of PEG-4000 and Carplex-80 as carrier in different ratios. Solid-state analyses of SDA were performed to characterize the physicochemical properties of newly developed SDA by differential scanning calorimetry (DSC), powder x-ray diffractometry (PXRD), fourier transformed infrared spectra (FTIR) and scanning electron microscopy (SEM). DSC and PXRD showed that the crystallinity of drugs was notably decreased during the preparation of SDA. FTIR and SEM also demonstrated the conversion of ATV from amorphous to crystalline state resulting in improved solubility. Among formulations, SDA-5 showed significant enhancement of in-vitro drug release (around 2 fold higher) as compared to pure ATV. Further, in-vivo study was conducted to evaluate the effects of a newly developed ATV loaded solid dispersion on glycemic control, lipid profile, liver enzyme and histopathology in STZ induced diabetic mice. Oral administration of SDA significantly lowered the blood glucose levels during the course of treatment. Treatment with SDA significantly improved lipid pro files better than ATV alone and the effect was dose-dependent. After one week of SDA treatment significantly decreased liver weights as result of lipid clearance and the hepatocytes regained their normal architecture, and these beneficial effects can be correlated with the reduction of SGPT levels. The results demonstrated that, SDA exerted better glycemic control, lipid lowering effect and organ protection (liver and pancreas) than that of conventional ATV in STZ induced diabetic mice. The mechanism by which SDA conferred better improvement in diabetic conditions can be partially explained by enhancement of solubility and dissolution rate when ATV is loaded in solid dispersion.
Lipinski, C.A. and Lombardo, F. (1997) Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings. Advanced Drug Delivery Reviews, 23, 3-25. https://doi.org/10.1016/S0169-409X(96)00423-1
Leuner, C. and Dressman, J. (2000) Improving Drug Solubility for Oral Delivery Using Solid Dispersions. European Journal of Pharmaceutics and Biopharmaceutics, 50, 47-60. https://doi.org/10.1016/S0939-6411(00)00076-X
Malhotra, H.S. and Goa, K.L. (2001) Atorvastatin: An Updated Review of Its Pharmacological Properties and Use in Dyslipidaemia. Drugs, 61, 1835-1881. https://doi.org/10.2165/00003495-200161120-00012
Lea, A.P. and McTavish, D. (1997) Atorvastatin: A Review of Its Pharmacology and Therapeutic Potential in the Management of Hyperlipidemias. Drugs, 53, 828-847. https://doi.org/10.2165/00003495-199753050-00011
Lennernas, H. (2003) Clinical Pharmacokinetics of Atorvastatin. Clinical Pharmacokinetics, 42, 1141-1160. https://doi.org/10.2165/00003088-200342130-00005
Taylor, F., Huffman, M.D., Macedo, A.F., Moore, T.H., Burke, M., Davey Smith, G., Ward, K. and Ebrahim, S. (2013) Statins for the Primary Prevention of Cardiovascular Disease. Cochrane Database of Systematic Reviews, 1, CD004816.
Croom, K.F. and Plosker, G.L. (2005) Atorvastatin: A Review of Its Use in the Primary Prevention of Cardiovascular Events in Patients with Type 2 Diabetes Mellitus. Drugs, 65, 137-152. https://doi.org/10.2165/00003495-200565010-00015
Curran, M.P. (2010) Amlodipine/Atorvastatin: A Review of Its Use in the Treatment of Hypertension and Dyslipidaemia and the Prevention of Cardiovascular Disease. Drugs, 70, 191-213. https://doi.org/10.2165/11204420-000000000-00000
Matafome, P., Monteiro, P., Nunes, E., Louro, T., Amaral, C., Moedas, A.R., Gonçalves, L., Providencia, L. and Seiça, R. (2008) Therapeutic Association of Atorvastatin and Insulin in Cardiac Ischemia: Study in a Model of Type 2 Diabetes with Hyperlipidemia. Pharmacological Research, 58, 208-214. https://doi.org/10.1016/j.phrs.2008.07.005
Gibaldi, M. and Feldman, S. (1970) Mechanisms of Surfactant Effects on Drug Absorption. Journal of Pharmaceutical Sciences, 59, 579-589. https://doi.org/10.1002/jps.2600590502
Higuchi, W.I., Lau, P.K., Higuchi, T. and Shell, J.W. (1963) Polymorphism and Drugs Availability, Solubility Relationships in the Methylprednisolone System. Journal of Pharmaceutical Sciences, 52, 150-153. https://doi.org/10.1002/jps.2600520210
Fincher, J.H. (1968) Particle Size of the Drugs and Its Relationships to Absorptions and Activity. Journal of Pharmaceutical Sciences, 57, 1825-1835. https://doi.org/10.1002/jps.2600571102
Louis, D. (2016) Formulations and Evaluation of Nanocrystals of a Lipid Lowering Agent. Iranian Journal of Pharmaceutical Research, 15, 71-82.
Bathool, A., Vishakante, G.D., Khan, M.S. and Shivakumar, H.G. (2012) Development and Characterization of Atorvastatin Calcium Loaded Chitosan Nanoparticle for Sustain Drug Delivery. Advanced Materials Letters, 3, 466-470. https://doi.org/10.5185/amlett.2012.icnano.153
Narasaiah, L., Reddy, K., Raj Kumar, K., Rao, S. and Reddy, V. (2010) Enhanced Dissolution Rate of Atorvastatin Calcium Using Solid Dispersion with PEG-6000 by Dropping Method. Journal of Pharmaceutical Sciences and Research, 2, 484-491.
Sharma, B., Saini, V. and Sharma, A. (2012) Preparation, Characterization and In-Vitro Evaluation of Atorvastatin Calcium Solid Dispersions with Various Hydrophilic Polymers and Its FDT Formulation. Journal of Current Pharma Research, 2, 620-630.
Patelia, E.M., Thakur, R. and Patel, J. (2013) Solubility Enhancement of Poor Water Soluble Atorvastatin Calcium Using Solid Dispersion Techniques. Journal of Medicinal Chemistry, 3, 4.
Jahan, R., Islam, M.S., Tanwir, A. and Chowdhury, J.A. (2013) In Vitro Dissolution Study of Atorvastatin Binary Solid Dispersion. Journal of Advanced Pharmaceutical Technology & Research, 4, 18-24. https://doi.org/10.4103/2231-4040.107496
Taral Mayur, N. (2015) Solubility Enhancement of Atorvastatin Calcium by Using Microwave Assisted Solid Dispersion Preparation Method. International Journal of Pharmaceutical Research & Allied Sciences, 4, 51-56.
Thirupathaiah, A. and Shyam Sunder, R. (2016) Enhancement of Solubility and Dissolution of Atorvastatin by Solid Dispersion Technique with Novel Carriers. Der Pharmacia Lettre, 8, 180-191.
Shamsuddin, Fazil, M., Ansari, S.H. and Ali, J. (2016) Atorvastatin Solid Dispersion for Bioavailability Enhancement. Journal of Advanced Pharmaceutical Technology & Research, 7, 22-26. https://doi.org/10.4103/2231-4040.169873
Barzegar-Jalali, A.J.M., Garjani, A., Javadzadeh, Y., Hamishehkar, H., Asadpour- Zeynali, K. and Adibkia, K. (2016) Evaluation of Physicochemical Properties and in Vivo Efficiency of Atorvastatin Calcium/Ezetimibe Solid Dispersions. European Journal of Pharmaceutical Sciences, 82, 21-30. https://doi.org/10.1016/j.ejps.2015.11.007
Arunkumar, N., Deecaraman, M., Rani, C., Mohanraj, K.P. and Venkates Kumar, K. (2009) Preparation and Solid State Characterization of Atorvastatin Nanosuspensions for Enhanced Solubility and Dissolution. International Journal of PharmTech Research, 1, 1725-1730.
Chouksey, R., Jain, A.K., Pandey, H. and Maithil, A. (2011) Development and Bioavailability Studies of Atorvastatin Nanoemulsion. International Journal of Pharmacy and Life Sciences, 2, 982-998.
Deeds, M.C., Anderson, J.M., Armstrong, A.S., Gastineau, D.A., Hiddinga, H.J., Jahangir, A., Eberhardt, N.L. and Kudva, Y.C. (2011) Single Dose Streptozotocin-Induced Diabetes: Considerations for Study Design in Islet Transplantation Models. Laboratory Animals, 45, 131-140. https://doi.org/10.1258/la.2010.010090
Morton, D.B., Abbot, D., Barcaly, R., Close, B.S., Ewbank, R., Gask, D., Heath, M., Mattic, S., Poole, T., Seamer, J. and Sothee, J. (1993) Removal of Blood from Laboratory Mammals and Birds. Laboratory Animals, 27, 1-22. https://doi.org/10.1258/002367793781082412
Fukuyama, N., Homma, K., Wakana, N., Kudo, K., Suyama, A., Ohazama, H., Tsuji, C., Ishiwata, K., Eguchi, Y., Nakazawa, H. and Tanaka, E. (2008) Validation of the Friedewaldequation for Evaluation of Plasma LDL-Cholesterol. Journal of Clinical Biochemistry and Nutrition, 43, 1-5. https://doi.org/10.3164/jcbn.2008036
Patidar, K. (2010) Solid Dispersion Technology: A Boon for Poorly Water Soluble Drugs. Indian Journal of Novel Drug Delivery, 3, 83-90.
Vasconcelos, T., Sarmento, B. and Costa, P. (2007) Solid Dispersions as Strategy to Improve Oral Bioavailability of Poor Water Soluble Drugs. Drug Discovery Today, 12, 1068-1075. https://doi.org/10.1016/j.drudis.2007.09.005
Planinsek, O., Kovacic, B. and Vrecer, F. (2011) Carvedilol Dissolution Improvement by Preparation of Solid Dispersions with Porous Silica. International Journal of Pharmaceutics, 406, 41-48. https://doi.org/10.1016/j.ijpharm.2010.12.035
Matsumoto, K., Nakai, Y., Yonemochi, E., Oguchi, T. and Yamamoto, K. (1998) Effect of Pore Size on the Gaseous Adsorption of Ethenzamide on Porous Crystalline Cellulose and the Physicochemical Stability of Ethenzamide after Storage. Chemical and Pharmaceutical Bulletin, 46, 314-318. https://doi.org/10.1248/cpb.46.314
Kinoshita, M., Baba, K., Nagayasu, A., Yamabe, K., Shimooka, T., Takeuchi, Y., Azuma, M., Houchi, H. and Minakuchi, K. (2002) Improvement of Solubility and Oral Bioavailability of a Poorly Water Soluble Drug, TAS-301, by Its Melt Adsorption on a Porous Calcium Silicate. Journal of Pharmaceutical Sciences, 91, 362-370. https://doi.org/10.1002/jps.10026
Maurya, D., Belgamwar, V. and Tekade, A. (2010) Microwave Induced Solubility Enhancement of Poorly Water Soluble Atorvastatin Calcium. Journal of Pharmacy and Pharmacology, 62, 1599-1606. https://doi.org/10.1111/j.2042-7158.2010.01187.x
Hamilton, S.J. and Watts, G.F. (2013) Endothelial Dysfunction in Diabetes: Pathogenesis, Significance, and Treatment. The Review of Diabetic Studies, 10, 133-156.
Chen, Y.C. and Tseng, C.H. (2013) Dyslipidemia, Kidney Disease and Cardiovascular Disease in Diabetic Patients. The Review of Diabetic Studies, 10, 88-100. https://doi.org/10.1900/RDS.2013.10.88
Chang, Y.C. and Wu, W.C. (2013) Dyslipidemia and Diabetic Nephropathy. The Review of Diabetic Studies, 10, 121-132. https://doi.org/10.1900/RDS.2013.10.121
Stein, E.A. (2009) Low Density Lipoprotein Cholesterol Reduction and Prevention of Cardiovascular Disease. Mayo Clinic Proceedings, 84, 307-309. https://doi.org/10.1016/S0025-6196(11)60537-5
Ahmeda, D., Sharmab, M. and Pillaib, K.K. (2012) The Effects of Triple vs. Dual Andmonotherapy with Rosiglitazone, Glimepiride, and Atorvastatin on Lipid Profile Andglycemic Control in Type 2 Diabetes Mellitusrats. Fundamental & Clinical Pharmacology, 26, 621-631. https://doi.org/10.1111/j.1472-8206.2011.00960.x
Singh, A., Bhat, T.K. and Sharma, O.P. (2011) Clinical Biochemistry of Hepatotoxicity. Journal of Clinical Toxicology, S, 1-19.