• RAKESH V. MISHRA Department of Pharmaceutics, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune 411018, Maharashtra, India
  • SHASHIKANT N. DHOLE Department of Pharmaceutics, Modern College of Pharmacy, Moshi, Pune 412105, Maharashtra, India



Anagliptin, Metabolic syndrome, Floating drug delivery system, Pellets and Spheronization


Objective: The present research aims to design and optimize gastroretentive floating pellets of anagliptin (a dipeptidyl peptidase-4 inhibitor), so as to reduce P-Glycoprotein (PGP)–mediated efflux in the intestine hence to improve oral bioavailability.

Methods: The drug-containing core pellets were prepared by extrusion and spheronization process followed by subsequent coating with three successive layers i.e. Eudragit RS 100, sodium bicarbonate (NaHCO3): hydroxypropyl methylcellulose E5LV (HPMC E5LV) and Eudragit RL 100 using fluidized bed processor. A 3 level 3 factor box-behnken design was adopted to investigate the effect of Eudragit RS 100, NaHCO3: HPMC E5LVand Eudragit RL 100 on floating lag time and drug release at 10 h. Desirability function under numerical optimization technique was used to identify the optimum formulation.

Results: The study reveals the significant effect of the amount of NaHCO3 and coating level of polymers on floating lag time and drug release. The optimum system could float within 4 min and exhibited more than 85% drug release in 10 h. The pharmacokinetic study conducted in male Wistar rats indicated 2.51 fold increase in relative bioavailability of optimized formulation compare to anagliptin drug. Formulated anagliptin pellets were evaluated in cafeteria diet-induced metabolic syndrome model in male Wistar rats. Anagliptin floating pellets treatment compared to cafeteria diet group significantly inhibited increase in body weight (238.79±2.52 g vs. 277.98±3.69 g, P<0.001), calorie intake (2283.99 kcal vs. 3086.05 kcal, P<0.05) and serum levels of total cholesterol (95.19±0.61 mg/dl vs. 110.04±1.31 mg/dl, P<0.01), triglycerides (96.12±1.25 mg/dl vs. 105.99±1.29 mg/dl, P<0.01) while high-density lipoproteins levels were improved (42.15±0.92 mg/dl vs. 30.92±0.77 mg/dl, P<0.01) indicated its hypophagic and anti-hyperlipidemic effects.

Conclusion: The gastroretentive floating pellets of anagliptin was obtained and could be a promising technique to deliver anagliptin with improved bioavailability in the management of the metabolic syndrome.


Van Wormer JJ, Boucher JL, Sidebottom AC, Sillah A, Knickelbine T. Lifestyle changes and prevention of metabolic syndrome in the heart of New Ulm project. Prev Med Rep 2017;6:242-5.

Hu G, Qiao Q, Tuomilehto J, Balkau B, Borch-Johnsen K, Pyorala K. Prevalence of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in nondiabetic European men and women. Arch Intern Med 2004;164:1066-76.

Sattigeri JA, Sethi S, Davis JA, Sahadat A, Rayasam GV, Jadhav BG, et al. Approaches towards the development of chimeric DPP4/ACE inhibitors for treating metabolic syndrome. Bioorg Med Chem Lett 2017;27:2313-8.

Mishra RV, Dhole SN. Dipeptidyl peptidase-4 inhibitors: potential for the treatment of metabolic syndrome and developed formulation approaches. Asian J Pharm Clin Res 2017;10:20-6.

Furuta S, Tamura M, Hirooka H, Mizuno Y, Miyoshi M, Furuta Y. The pharmacokinetic disposition of anagliptin, a novel dipeptidyl peptidase-4 inhibitor, in rats and dogs. Eur J Drug Metab Pharmacokinet 2013;38:87–96.

Kagan L, Dreifinger T, Mager D, Hoffman A. Role of P-glycoprotein in region-specific gastrointestinal absorption of talinolol in rats. Drug Metabol Disposition 2010;38:1560-6.

Hoffman A, Stepensky D, Lavy E, Eyal S, Klausner E, Friedman M. Pharmacokinetic and pharmacodynamic aspects of gastroretentive dosage forms. Int J Pharm 2004;277:141–53.

Streubel A, Siepmann J, Bodmeier R. Gastroretentive drug delivery systems. Expert Opin Drug Delivery 2006;3:217–33.

Kagan L, Hoffman A. Systems for region selective drug delivery in the gastrointestinal tract: biopharmaceutical considerations. Expert Opin Drug Delivery 2008;5:681–92.

Moes AJ. Gastroretentive dosage forms. Crit Rev Ther Drug Carrier Syst 1993;10:143–95.

Kotreka UK, Adeyeye MC. Gastroretentive floating drug-delivery systems: a critical review. Crit Rev Ther Drug Carrier Syst 2011;28:47–99.

Reddy LH, Murthy RS. Floating dosage systems in drug delivery. Crit Rev Ther Drug Carrier Syst 2002;19:36.

Strusi OL, Sonvico F, Bettini R, Santi P, Colombo G, Barata P, et al. Module assemblage technology for floating systems: in vitro flotation and in vivo gastro-retention. J Controlled Release 2008;129:88–92.

Singh BN, Kim KH. Floating drug delivery systems: an approach to oral controlled drug delivery via gastric retention. J Controlled Release 2000;63:235–59.

Badve SS, Sher P, Korde A, Pawar AP. Development of hollow/porous calcium pectinate beads for floating-pulsatile drug delivery. Eur J Pharm Biopharm 2007;65:85-93.

Ichikawa M, Watanabe S, Miyake S. A new multiple-unit oral floating dosage system. I: preparation and in vitro evaluation of floating and sustained-release characteristics. J Pharm Sci 1991;80:1062-6.

Bulgarelli E, Forni F, Bernabei MT. Effect of matrix composition and process conditions on casein-gelatin beads floating properties. Int J Pharm 2000;198:157-65.

Iannuccelli V, Coppi G, Bernabei MT, Cameroni R. Air compartment multiple-unit system for the prolonged gastric residence. Part I. formulation study. Int J Pharm 1998;174:47-54.

Streubel A, Siepmann J, Bodmeier R. Multiple units gastroretentive drug delivery systems: a new preparation method for low-density microparticles. J Microencapsul 2003;20:329-47.

Kim SM, Kim JS, Hwang SJ. The effect of sodium alginate on physical and dissolution properties of Surelease matrix pellets prepared by a novel pelletizer. Chem Pharm Bull 2007; 55:1631–4.

Parmar SS, Mishra RV, Shirolkar SV. Spherical agglomeration a novel approach for solubility and dissolution enhancement of simvastatin. Asian J Pharm Clin Res 2016;9:65-72.

Jaya S, Amala V. Formulation and in vitro evaluation of oral disintegrating tablets of amlodipine besylate. Int J Appl Pharm 2019;11:49-54.

Ahmed AA, Wedad KA, Fouad AA. Formulation and evaluation of prochlorperazine maleate sustained release floating tablet. Int J Pharm Pharm Sci 2017;9:89-98.

Raval MK, Ramani RV, Sheth NR. Formulation and evaluation of sustained release enteric-coated pellets of budesonide for intestinal delivery. Int J Pharma Investig 2013;3:203-11.

Rajinikanth PS, Karunagaran LN, Balasubramaniam J, Mishra B. Formulation and evaluation of clarithromycin microspheres for the eradication of Helicobacter pylori. Chem Pharm Bull 2008;56:1658–64.

Kavita K, Puneeth K, Tamizh T. Development and evaluation of rosiglitazone maleate floating tablets. Int J Appl Pharm 2010;2:6-10.

Kauser F, Sadhana S. Development and evaluation of floating tablet of metoprolol succinate for increased bioavailability via in vivo study. Asian J Pharm Clin Res 2018;11:79-84.

Costa P, Lobo MS. Modeling and comparison of dissolution profiles. Eur J Pharm Sci 2001;13:123.

Ritger PL, Peppas NA. A simple equation for description of solute release. II. Fickian and anomalous release from swellable devices. J Controlled Release 1987;5:37.

Lopes CM, Lobo JM, Pinto JF, Costa P. Compressed minitablets as a biphasic delivery system. Int J Pharm 2006;323:93.

Korsmeyer RW, Gurny R, Doelkar E, Buri P, Peppas NA. Mechanism of solute release from porous hydrophilic polymers. Int J Pharm 1983;15:25.

Higuchi T. Mechanism of sustained action medication: theoretical analysis of rate release of solid drugs dispersed in solid matrices. J Pharm Sci 1963;52:1145–49.

Venkata MS, Sreenivasa NR, Ambedkar SS, Janaki BR, Murthyi VR. Statistical design and evaluation of a propranolol HCl gastric floating tablet. Acta Pharm Sin B 2012;2:60–9.

Sahoo J, Murthy PN, Biswal S, Sahoo SK, Mahapatra AK. Comparative study of propranolol hydrochloride release from matrix tablets with Kollidon®SR or hydroxypropyl methyl-cellulose. AAPS PharmSciTech 2008;9:577–82.

Kumar S, Alagawadi KR, Raghavendra M. Effect of argyreia speciosa root extract on cafeteria diet-induced obesity in rats. Indian J Pharmacol 2011;43:163-7.

Shikova A, Pozharitskayaa O, Makarovaa M, Kovalevaa M, Laaksob I, Damien H, et al. Effect of bergenia crassifolia L. extracts on weight gain and feeding behavior of rats with high-caloric diet-induced obesity. Phytomedicine 2012;19:1250–5.

Krogel I, Bodmeier R. Floating or pulsatile drug delivery systems based on coated effervescent cores. Int J Pharm 1999;187:175–84.



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