In-vitro – In-vivo Characterization of ‎Glimepiride Lipid Nanoparticulates ‎Prepared by Combined Approach of ‎Precipitation and Complexation

Document Type : Research Paper


Department of Pharmaceutics, Faculty of Pharmacy, Acharya & BM Reddy College of ‎Pharmacy, Soldevanahalli, Bengaluru 560 017, India


Novel lipid nanoparticulates (NCs) were developed by a combined approach of precipitation and complexation with an aim to improve the solubility, stability and targeting efficiency of glimepiride (GLP). GLP NCs were prepared by precipitation process using PEG 20000 and further complexed with phospholipon90G (P90G). The NCs were evaluated for physicochemical characterization, such as drug loading, saturation solubility (SS) and particle characterization studies. The solid state characterization studies were performed using X-ray powder diffractometry (XRPD), differential scanning calorimetry (DSC), infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Further in-vitro dissolution studies and in vivo (drug targeting) studies were also performed. Short term (3 months) stability studies were conducted on most satisfactory NCs. GLP P90G NCs exhibited three folds increase in saturation solubility. Particle size of NCs was ranging from between 210-240 nm. The dissolution and in vitro stability of NCs were superior compared to pure GLP. XRPD and DSC analysis proved that crystallinity prevailed in NCs, but with a slight change in crystal structure. SEM analysis indicated spherical shaped particles with a lipid coat. The NCs were found to be stable during the period of study. In vivo studies on optimized NCs showed slightly higher drug concentration (1.38 µg/ml) in pancreas of rat than that of pure GLP. It can be concluded that solubility and stability of GLPNCs were significantly improved by P90G complexation. Also, P90G (phospholipids) could be effectively used in enhancing the targeting efficiency and pharmacokinetics of glimepiride.


Shaik, R., Bilal, A. T., (2012). ‘‘Nanomedicine current trends in diabetes management’’, J. Nanomed. Nanotech., 3: 1-7.
Gangadhara, A. R., Subashini., (2014). “Transdermal Nanocarriers: New Challenges and Prospectives in the Treatment of Diabetes mellitus”, J. of Chem. and App. Biochem.,1: 1-11.
Silvio, E., Inzucchi., (2015). “Management of hyperglycemia in Type 2 diabetes. A patient centered approach”, Diabetes Care., 38: 140-149.
Sajeev, K. B., Saraswathi, R., (2013). “Development and characterization of lecithin stabilized glibenclamide nanocrystals for enhanced solubility and drug delivery”, Drug Delivery., 21: 173-184.
  Williams, R. O., (2012). “Preface in formulating poorly water-soluble drugs”, Springer, USA.
Thomas, T., Jennifer, B., (2012). “New formulation approaches to improve solubility and drug release from fixed dose combinations: case examples, Pioglitazone / glimepiride and ezetimibe / simvastatin”, Eur. J. Pharm. Biopharm., 84: 208-18.
Gülsun, T., Gürsoy, R. N., (2009). “Öner. Nanocrystal technology for oral delivery of poorly water soluble drugs”, J. Pharm. Sci., 34: 55-65.
Chen, H., Khemtong, C., Yang, X., (2011). “Nanonization strategies for poorly water soluble drugs”, Drug Discov. Today., 16: 354-60.
Faris, N. B., Müller, R. H., (2002). “Nanocrystals for poorly soluble drugs for oral administration”, New Drugs., 2: 20-21.
Melike, Ü., Gülgün, Y., (2007). “Importance of solid lipid nanoparticles (SLN) in various administration routes and future perspectives”, Int. J. Nanomed., 2: 289-300.
Mishra, B., Bhavesh, P.,(2010). “Colloidal nanocarriers- a review on formulation technology, types and applications towards targeted drug delivery”, Nanomed, Nanotechnol. Biomed., 6: 9-24.
Fillipos, K., Santipharp, P., (2007). “Nanosizing oral formulation development and biopharmaceutical evaluation”. Adv. Drug Deliver. Rev., 59: 631-644.
Faris, N. B., Rainer, R. H., (2002). “Nanocrystals technology drug delivery and clinical applications”. Int. J. of Nanomed., 3: 295-309.
Mohanraj, V. J., Chen, Y.,(2006). “Nanoparticles - A Review”, Trop. J. Pharm. Res., 5: 561-573.
Sandrine, D., Lucie, S., (2012). “Physico-chemical parameters that govern nanoparticles fate also dictate rules for their molecular evolution”, Adv. Drug Deliver. Rev., 64: 179-189.
Zheng, N., Gao, X., Song, Q., (2012). “Lipid - based liquid crystalline nanoparticles as oral drug delivery vehicles for poorly water - soluble drugs, cellular interaction and in vivo absorption”, Int. J. Nano. Med., 7: 3703-3718.
Huabing, C., Chalermachai, K., (2011). “Nanonization strategies for poorly water soluble drugs”, Drug Discov. Today., 16: 354-360.
Libo, W.,  Jian, Z., (2011). “Physical stability of nanoparticles”, Adv. Drug Deliver. Rev., 63: 456-469.
Frick, A., Moller, H., Wirbitzki, E., (1998). “Biopharmaceutical characterization of oral immediate release drug products. Invitro/invivo comparison of phenoxymethyl pencillin, glimepirdie and levofloxacin”. Eur. J. of Pharm. Biopharm., 46: 305-311.
Hai, W., Chad, D., (2008). “Physiochemical characterization of five glyburide powders. A BCS based approach to predict oral absorption”. Eur. J. of Pharm. Biopharm., 46: 305-311.
Patrick, J. C., Luigi, G. M., (2004). “Formulation design: new drugs from old. Drug discov. today, therap. and strategies., 1: 537-542.
O'Donnell, K. P., (2012).“Optimizing the formulation of poorly water - soluble drugs”., Springer, USA.
Otilia, M. K., (2005). “Role of nanotechnology in targeted drug delivery and imaging: a concise review”, Nanomed. Nanotechol. Biomed., 1: 193-212.
Melgardt, M. D., (2009). “Nanotechnology in drug delivery”., AAPS Press, USA.
Mishra, B., Bhavesh, P., (2010). “Colloidal nanocarriers: A review on formulation technology, types and applications towards targeted drug delivery”, Nanomed. Nanotechol. Biomed., 6: 9-24.
Shelesh, J., Swarnalata, S., (2010). “Type 2 Diabetes Mellitus - Its global prevalence and therapeutic strategies”, Diabetes Metab. Syndrome Clin. Res. Rev., 4: 48-56. 
Mihaela, M. M., Helen, L. M., (2011). Glimepiride, a novel sulfonylurea does not abolish myocardial protection afforded by either ischemic preconditioning or diazoxide, J. American Heart Association., 103: 3111-3116.
Rhoban, T., (2005). “The efficacy and safety of glimepiride in the management of Type II diabetes in Muslim patients during Ramadan”, Diabetes Care., 28: 421-422.
Vania B. B., (2010). “Preparation of PVP hyrogel nanoparticles using lecithin vesicles”, Quim. Nova., 33:2083-2087.
Tongying, J., Ning, H. (2012). “Enhanced dissolution rate and oral bioavailability of simvastin nanocrystals prepared by sonoprecipitation”, Drug Dev. Ind. Pharm., 38: 1230-1239.
Afe, H., Göpferich, A., (2008). “Polymer coating of quantum dots - a powerful tool towards diagnostics and sensorics”, Eur. J. Pharm. Biopharm., 68: 138-152.
Sohelia, K., Abbas, H. A., (2011) “New surface-modified solid lipid nanoparticles using N-glutaryl phosphatidylethanolamine as the outer shell”, Int. J. Nanomed., 6: 2393-2401.
Baliar, S., Biswal, S., (2009). “Physiochemical properties of glimepiride in solid dispersions with polyethylene glycol 20000”, Int. J. Pharm. Sci. Nano., 2: 537-543.
Blagden, N., Maras, M., (2007). “Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates”, Adv. Drug Deliver. Rev., 59: 617-630.
Fuminori, I., Hiroyuki, F., (2008). “Effect of polyethylene glycol on preparation of rifampicin-loaded PLGA microspheres with membrane emulsification technique”, Colloids Surf. B: Biointerfaces., 66: 65-70.
Min, S. K., Shun, J. J., (2008). “Preparation, characterization and in vivo evaluation of amorphous atrovastatin calcium nanoparticles using supercritical antisolvent (SAS) process”, Eur. J. Pharm. Biopharm., 69: 454-465. 
Hui, S. W., Kuhl, T. L., (1999). “Use of polyethyene glycol to control cell aggregation and fusion”. Colloids Surf. B: Biointerfaces., 4, 213-222. 
Shubhadeep, C., Subhabrota, M., (2010). “Statistical optimization of fixed dose combination of glimepiride and atrovastatin calcium in immediate release tablet formulation”, Int. J. Pharm. Sci., 2: 194-200. 
Korsmeyer, R. W., Gurny, R., (1983). “Mechanism of solute release from porous hydrophilic polymers”, Int. J. Pharm., 15: 25-35.
Kim, H., Fassihi, R., (1997). “Application of binary polymer system in drug release rate modulation and influence of formulation variables and hydrodynamic conditions on release kinetics”, J. Pharm. Sci., 86: 323-328.
Hörter, D., Dressman, J. B., (1997). “Influence of physiochemical properties on dissolution of drugs in the gastrointestinal tract”, Adv. Drug Deliver. Rev., 25: 3-14.  
Kaili, H., Shan, C., (2012). “Enhanced oral bioavailability of doxetaxel by lecithin nanoparticles: Preparation, in vitro and in vivo evaluation”. Int. J. Nano. Med.,7: 3537-3545
Zhipeng, C., Lu, X., (2012). “Novel materials which possess the ability to target liver cells”. Drug Delivery., 9: 649-656.
Sajeev, K. B., Saraswathi, R., (2011). “Formulation and evaluation of controlled release glimepiride osmotic systems”,Int. J. Pharm. Res., 3: 79-84.
Kaili, H., Shan, C., (2012). “Enhanced oral bioavailability of doxetaxel by lecithin nanoparticles: Preparation, in vitro and in vivo evaluation”, Int. J. Nano. Med. 7: 3537-3545.
Brown, N. J.,  Read, N. W., (1990). “Characteristics of lipid substance activating the ideal break in the rat”, Gut., 31: 1126-1129.
Jane, W., Sabine, G., (2008). “Physicochemical stability of phospholipid-dispersed suspensions of crystalline itraconazole”, Eur. J. Pharm. Biopharm., 69: 1104-1113.   
Robash, K. S., Keon., W. K. (2009). “Preparation and characterization of solid lipid nanoparticles loaded with doxorubicin”, Eur. J. Pharm. Sci., 37: 508-513.  
Müller, R. H., Jacobs, C., Kayser, O., (2001). “Nanosuspensions as particulate drug formulations in therapy, rationale for development and what we can expect for the future”, Adv. Drug Deliver. Rev., 47: 3-19.
Fuminori, I., Hiroyuki, F., (2008). “Effect of polyethylene glycol on preparation of rifampicin-loaded PLGA microspheres with membrane emulsification technique”. Colloids. Surf. B. Biointerfaces., 66: 65-70.
Avnesh, K., Sudesh, K. Y., (2010). “Biodegradable polymeric nanoparticles based drug delivery systems”, Colloids Surf. B. Biointerfaces., 75: 1-18.  
Marie, G., Angelica, V., (2008). “Nanoparticles for drug delivery: The need for precision in reporting particle size parameters”. Eur. J. Pharm. Biopharm., 69: 1-9.
Shasha, R., Yunmei, S., (2012). “Particle size reductions to the nanometer range a promising approach to improve buccal absorption of poorly water-soluble drugs”, Int. J. Nano. Med., 6: 1245-1251. 
Tamara, M. (2005). “Soluble polymer conjugates for drug delivery”, Drug Discov. Today Tech., 2: 15-20.
Anju, G., Singhvi, I., (2007). “Simultaneous spectrophotometric estimation of Rosiglitazone maleate and glimepiride in tablet dosage forms”, Indian J. Pharm. Sci., 69: 780-783.
Lisha, W., Yanxia, J., Wei, G., (2015). “Preparation, physical characterization and pharmacokinetic study of paclitaxel nanocrystals”, Drug. Dev. Ind. Pharm., 41: 1343-1352.
Yue, P. F., Yuan, H. L., (2010). “Process, optimization, characterization and evaluation in vivo of oxymatrine-phospholipid complex”, Int. J. Pharm., 387: 139-146. 
Yongxue, Z., Chunling, W., (2012). “A frustrating problem, accelerated blood clearance of PEGylated solid nanoparticles following subcutaneous injection in rats”, Eur. J. Pharm. Biopharm., 81: 506-513.
Fu, Q., Sun, J., Zhang, D., “Nimodipine nanocrystals for oral bioavailability improvement: preparation, characterization and pharmacokinetic studies”, Colloids Surf. B. Biointerfaces., 109: 161-166.
Tony, R., Elisabeth., (1991). “Determination of glibenclamide and its major metabolites in human serum and urine by column liquid chromatography”, J. Chrom., 564: 223-233.