DEVELOPMENT AND IN VITRO-IN VIVO EVALUATION OF GLIPIZIDE LOADED MULTIUNIT PULSATILE FORMULATION FOR TREATMENT OF DIABETIC PATIENTS
The aim of the present study was to develop oral multiparticulate pulsatile drug delivery system for hypoglycemic agent â€˜glipizideâ€™. Time dependent rupturable system was selected for delivering glipizide in a pulsatile pattern. In the present study, two types of particles were prepared i. e. Type 1 (immediate release type) and Type 2 (delayed release type). Extrusion and spheronization process was selected to prepare particles, wherein lactose and microcrystalline cellulose mixture (2:1) was used as processing aid. Various parameters of extrusion and spheronization process were optimized in order to meet desired particle size distribution, shape and flow properties. Immediate release Type 1 particle was optimized to achieve more than 80% drug release within 30 min for which surfactant approach was employed to overcome the dissolution rate related issue of the glipizide. Delayed release pattern of Type 2 particles was achieved by coating hydroxypropylmethylcellulose and ethyl cellulose. Various coating parameters were optimized to attain efficient coating of the particles. Different concentrations of hydroxypropylmethylcellulose (5 and 3.5% w/w E-15 grade) and ethyl cellulose (5 and 3% w/w) were studied for release pattern for Type 2 particles. Final formulation was characterized using for particles size, flow properties and surface morphology. To examine the drug release, dissolution studies were performed. Pharmacokinetics studies in Sprague Dawley rats reveal improved oral bioavailability of glipizide following oral administration.
2. Gaba P, Singh S, Gaba M, Gupta GD. Galactomannan gum coated mucoadhesive microspheres of glipizide for treatment of type 2 diabetes mellitus: in vitro and in vivo evaluation. Saudi Pharm J 2011;19:143-52.
3. Goyal S, Rai GK, Narang RK, Rajesh KS. Sulfonylureas for antidiabetic therapy, an overview for glipizide. Int J Pharm Pharm Sci 2010;2:1-6.
4. Thombre AG, Denoto AR, Gibbes DC. Delivery of glipizide from asymmetric membrane capsules using encapsulated excipients. J Control Release 1999;60:333-41.
5. Chowdary KPR, Balatripura G. Design and in vitro evaluation of mucoadhesive controlled release oral tablets of glipizide. Ind J Pharm Sci 2003;65:591-4.
6. Chowdary KPR, Rao YS. Design and in vitro and in vivo evaluation of mucoadhesive microcapsules of glipizide for oral controlled release: a technical note. AAPS Pharm Sci Tech 2003;4:39.
7. Choudhary D, Kumar S, Gupta GD. Enhancement of solubility and dissolution of glipizide by solid dispersion (kneading) technique. Asian J Pharm 2009;3:245â€“51.
8. Renuka, Singh SK, Gulati M, Kaur I. Characterization of solid state forms of glipizide. Powder Technol 2014;264:365â€“76.
9. Gharge V, Peeyush SP, Gonjari I, Bhandari A. Multiple-unit controlled release platform formulation by wruster process. Int J Pharm Pharm Sci 2014;6:107-13.
10. Enayatifard R, Saeedi M, Akbari J, Tabatabaee YH. Effect of hydroxypropyl methylcellulose and ethyl cellulose content on release profile and kinetics of diltiazem HCL from matrices. Trop J Pharm Res 2009;8:425-32.
11. Pandit AP, Shinde RD. Development and in vitro evaluation of sustained release multiparticulate tablet of freely water soluble drug. Braz. J Pharm Sci 2010;46:463-71.
12. Guo J-H. Effects of plasticizers on water permeation and mechanical properties of cellulose acetate: antiplasticization in slightly plasticized polymer film. Drug Dev Ind Pharm 993;19:1541-55.
13. Tuba C S-T, Hascicek C, Gonul N. Ethylcellulose-based matrix-type microspheres: influence of plasticizer ratio as pore-forming agent. AAPS Pharm Sci Tech 2011;12:1127-35.
14. Carr RL. Classifying flow properties of powder. Chem Eng 1965;72