PP  Vol.5 No.13 , December 2014
Design and in Vitro Evaluation of Eudragit® S100/Lipid Based Simvastatin Chronotherapeutic Drug Delivery System
Abstract: The present study was undertaken to 1) formulate a pulsatile colonic delivery of simvastatin (SIM) as chronotherapy for treatment of hypercholesterolemia, and 2) enhance the dissolution profile of the prepared SIM chronotherapeutic system. Lipid based formulations were utilized to formulate SIM in capsule dosage form coated with Eudragit® S100. SIM was formulated using different percentages of Cremophor EL40, Capmul MCM EP and PEG 400. SIM coated capsules (SIMcc) were evaluated for drug release in different pH media. The results showed that SIMcc were able to withstand the acidic pH for 2 hours. Drug release rate was higher (88%) from SIMcc containing 10% polyethylene glycol (PEG) 400. In conclusion, Eudragit® S100 as time-dependent and site specific polymer retards SIM release from coated capsules; hence SIMcc could be considered as successful pulsatile treatment of hypercholesterolemia. Also, dissolution profile of lipid based SIMcc was enhanced in comparison with that of SIM filled capsules.
Cite this paper: Taha, E. (2014) Design and in Vitro Evaluation of Eudragit® S100/Lipid Based Simvastatin Chronotherapeutic Drug Delivery System. Pharmacology & Pharmacy, 5, 1157-1162. doi: 10.4236/pp.2014.513126.

[1]   Bussemer, T., Otto, I. and Bodmeier, R. (2001) Pulsatile Drug-Delivery Systems. Critical Reviews in Therapeutic Drug Carrier Systems, 18, 433-458.

[2]   Mandal, A.S., Biswas, N., Karim, K.M., Guha, A., Chatterjee, S., Behera, M. and Kuotsu, K. (2010) Drug Delivery System Based on Chronobiology—A Review. Journal of Controlled Release, 147, 314-325.

[3]   Jones, P. and Schoeller, D. (1990) Evidence for Diurnal Periodicity in Human Cholesterol Synthesis. Journal of Lipid Research, 31, 667-673.

[4]   Kamal, S.M. (2011) Effects of Single-Dose Morning and Evening Administration of Pravastatin on Antioxidant Markers in Cholesterol-Fed Rabbits. Journal of Experimental Pharmacology, 3, 51-58.

[5]   Liao, J.K. (2005) Clinical Implications for Statin Pleiotropy. Current Opinion in Lipidology, 16, 624-629.

[6]   Smolensky, M.H. and Peppas, N.A. (2007) Chronobiology, Drug Delivery, and Chronotherapeutics. Advanced Drug Delivery Reviews, 59, 828-851.

[7]   Barakat, N.S., Al-Suwayeh, S.A., Taha, E.I. and Bakry Yassin, A.E. (2011) A New Pressure-Controlled Colon Delivery Capsule for Chronotherapeutic Treatment of Nocturnal Asthma. Journal of Drug Targeting, 19, 365-372.

[8]   Yang, L., Chu, J.S. and Fix, J.A. (2002) Colon-Specific Drug Delivery: New Approaches and in Vitro/in Vivo Evaluation. International Journal of Pharmaceutics, 235, 1-15.

[9]   Ghimire, M., McInnes, F.J., Watson, D.G., Mullen, A.B. and Stevens, H.N. (2007) In-Vitro/In-Vivo Correlation of Pulsatile Drug Release from Presscoated Tablet Formulations: A Pharmacoscintigraphic Study in the Beagle Dog. European Journal of Pharmaceutics and Biopharmaceutics, 67, 515-523.

[10]   Niwa, K., Takaya, T., Morimoto, T. and Takada, K. (1995) Preparation and Evaluation of a Time-Controlled Release Capsule Made of Ethylcellulose for Colon Delivery of Drugs. Journal of Drug Targeting, 3, 83-89.

[11]   De Oliveira, H.P., Albuquerque Jr., J.J., Nogueiras, C. and Rieumont, J. (2009) Physical Chemistry Behavior of Enteric Polymer in Drug Release Systems. International Journal of Pharmaceutics, 366, 185-189.

[12]   Kassan, M., Montero, M.J. and Sevilla, M.A. (2009) Chronic Treatment with Pravastatin Prevents Early Cardiovascular Changes in Spontaneously Hypertensive Rats. British Journal of Pharmacology, 158, 541-547.

[13]   Stella, V.J. and Nti-Addae, K.W. (2007) Prodrug Strategies to Overcome Poor Water Solubility. Advanced Drug Delivery Reviews, 59, 677-694.

[14]   Chaumeil, J.C. (1998) Micronization: A Method of Improving the Bioavailability of Poorly Soluble Drugs. Methods and Findings in Experimental and Clinical Pharmacology, 20, 211-215.

[15]   Brewster, M.E. and Loftsson, T. (2007) Cyclodextrins as Pharmaceutical Solubilizers. Advanced Drug Delivery Reviews, 59, 645-666.

[16]   Pouton, C.W. and Porter, C.J. (2008) Formulation of Lipid-Based Delivery Systems for Oral Administration: Materials, Methods and Strategies. Advanced Drug Delivery Reviews, 60, 625-637.

[17]   Humberstone, A. and Charman, W.N. (1997) Lipid-Based Vehicles for the Oral Delivery of Poorly Water Soluble Drugs. Advanced Drug Delivery Reviews, 25, 103-128.

[18]   Zhao, X., Li, G., Zhang, L., Tao, X., Guan, T., Hong, M. and Tang, X. (2010) Preparation and Evaluation of Nicotinic Acid Sustained-Release Pellets Combined with Immediate Release Simvastatin. International Journal of Pharmaceutics, 15, 42-48.

[19]   Pouton, C.W. (2000) Lipid Formulations for Oral Administration of Drugs: Non-Emulsifying, Self-Emulsifying and “Self-Microemulsifying” Drug Delivery Systems. European Journal of Pharmaceutical Sciences, 11, S93-S98.

[20]   Pouton, C.W. (2006) Formulation of Poorly Water-Soluble Drugs for Oral Administration: Physicochemical and Physiological Issues and the Lipid Formulation Classification System. European Journal of Pharmaceutical Sciences, 29, 278-287.

[21]   Sermkaew, N., Ketjinda, W., Boonme, P., Phadoongsombut, N. and Wiwattanapatapee, R. (2013) Liquid and Solid Self-Microemulsifying Drug Delivery Systems for Improving the Oral Bioavailability of Andrographolide from a Crude Extract of Andrographis paniculata. European Journal of Pharmaceutical Sciences, 50, 459-466.

[22]   Do, T.T., Van Speybroeck, M., Mols, R., Annaert, P., Martens, J., Van Humbeeck, J., Vermant, J., Augustijns, P. and Van den Mooter, G. (2011) The Conflict between in Vitro Release Studies in Human Biorelevant Media and the in Vivo Exposure in Rats of the Lipophilic Compound Fenofibrate. International Journal of Pharmaceutics, 414, 118-124.

[23]   Tyagi, V.K., Singh, D. and Pathak, K. (2013) Semisolid Matrix-Filled Hard Gelatin Capsules for Rapid Dissolution of Amlodipine Besilate: Development and Assessment. Journal of Advanced Pharmaceutical Technology & Research, 4, 42-49.

[24]   Rahman, Z., Siddiqui, A. and Khan, M.A. (2013) Assessing the Impact of Nimodipine Devitrification in the Ternary Cosolvent System through Quality by Design Approach. International Journal of Pharmaceutics, 455, 113-123.

[25]   Soni, M.L., Namdeo, K.P., Jain, S.K., Gupta, M., Dangi, J.S., Kumar, M. and Dangi, Y.S. (2011) pH-Enzyme Di-Dependent Chronotherapeutic Drug Delivery System of Theophylline for Nocturnal Asthma. Chemical & Pharmaceutical Bulletin, 59, 191-195.

[26]   Ali, J., Saigal, N., Qureshi, M.J., Baboota, S. and Ahuja, A. (2010) Chronopharmaceutics: A Promising Drug Delivery Finding of the Last Two Decades. Recent Patents on Drug Delivery & Formulation, 4, 129-144.

[27]   Taha, E.I. (2014) Bioavailability Assessment of Hydroxymethylglutaryl Coenzyme A Reductase Inhibitor Utilizing Pulsatile Drug Delivery System: A Pilot Study. Drug Delivery, 7, 1-5.