PREPARATION, CHARACTERISATION AND EVALUATION OF ROPINIROLE HYDROCHLORIDE LOADED CONTROLLED RELEASE MICROSPHERES USING SOLVENT EVAPORATION TECHNIQUE
Objective: The major objective of the research work was to design, characterise and evaluate controlled release microspheres of ropinirole hydrochloride by using non-aqueous solvent evaporation technique to facilitate the delivery of the drug at a predetermined rate for a specific period of time.
Methods: Ropinirole hydrochloride microspheres were prepared by using different low-density polymers such as eudragit RL 100, eudragit RS 100 and ethylcellulose either alone or in combination with the help of non-aqueous solvent evaporation technique. All the formulated microparticles were subjected to various evaluation parameters such as particle size analysis, micrometric properties, drug entrapment efficiency, percentage drug loading, percentage yield and in vitro drug release study. The compatibility of the drug and polymers was confirmed by physical compatibility study, fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and x-ray diffraction study (XRD). The formation of the most optimized batch of the microsphere (F12) was confirmed by scanning electron microscopy (SEM), DSC, FTIR, and XRD. In vitro drug release study and in vitro drug release kinetics study of the formulated microspheres were also carried out.
Results: Drug-polymer compatibility studies performed with the help of FTIR and DSC indicated that there were no interactions. Results revealed that non-aqueous solvent evaporation technique was a suitable technique for the preparation of microspheres as most of the formulations were discrete, free-flowing and spherical in shape with a good yield of 55.67% to 80.09%, percentage drug loading of 35.52% to 94.50% and percentage drug entrapment efficiency of 36.24% to 95.07%. Different drug-polymer ratios, as well as the combination of polymers, played a significant role in the variation of over-all characteristics of formulations. Based on the data of various evaluation parameters such as particle size analysis, percentage drug loading, percentage drug entrapment, percentage yield, rheological studies and in vitro drug release characteristics, formulation F12 was found to fulfil the criteria of ideal controlled release drug delivery system. F12 showed controlled release till the 14th hour (97.99%) and its in vitro release kinetics was best explained by zero-order kinetics and followed Korsemeyer-Pappas model (Non-Fickian mechanism). SEM of F12 revealed the formation of spherical structures. The FTIR study of F12 confirmed the stable nature of ropinirole in the drug-loaded microspheres. DSC and XRD patterns showed that ropinirole hydrochloride was dispersed at the molecular level in the polymer matrix.
Conclusion: The controlled release microparticles were successfully prepared and from this study, it was concluded that the developed microspheres of ropinirole hydrochloride can be used for controlled drug release to improve the bioavailability and patient compliance and to maintain a constant drug level in the blood target tissue by releasing the drug in zero order pattern.
2. Durgapal S, Mukherjee S, Goswami L. Preparation, characterization and evaluation of floating microparticles of ciprofloxacin. Int J Appl Pharm 2017;9:1-8.
3. Bhosale NR, Hardikar SR, Ashok BV. Formulation and evaluation of transdermal patches of ropinirole HCl. Res J Pharm Biol Chem Sci 2011;2:138-48.
4. Vyas SP, Khar RK. Controlled drug delivery. Vallabh prakashan; 2008. p. 412-3.
5. Baveja K, Ranga Rao KV, Kumar Y. Microencapsulation of soluble pharmaceuticals. J Microencapsul 1986;3:33â€“7.
6. Sharma A, Khatri K, Patil UK. Nasal route: a potential alternative for antiparkinsonism drug delivery. Int J PharmTech Res 2008;2:2291-306.
7. Azeem A, Iqbal Z, Ahmad FJ, Khar RK, Talegaonkar S. Development and validation of a stability-indicating method for determination of Ropinirole in the bulk drug and in pharmaceutical dosage forms. Acta Chromatogr 2008;20:95â€“107.
8. Tahami KA. Preparation, characterization, and in vitro release of ketoprofen loaded alginate microspheres. Int J Appl Pharm 2014;6:9-12.
9. Gowda DV, Shivakumar HG. Preparation and evaluation of waxes/fat microspheres loaded with lithium carbonate for controlled release. Indian J Pharm Sci 2007;69:251â€“6.
10. Kim BK, Hwang SJ, Park JB, Park HJ. Preparation and characterization of drug-loaded polymethacrylate microspheres by an emulsion solvent evaporation method. J Microencapsul 2002;19:811â€“22.
11. Balaji A, Mantry S. Formulation, design and characterization of ropinirole hydrochloride microsphere for intranasal delivery. Asian J Pharm Clin Res 2017;10:195-203.
12. Agnihotri N, Mishra R, Goda C, Arora M. Microencapsulationâ€“a novel approach to drug delivery: a review. Indo Global J Pharm Sci 2012;2:1-20.
13. Kalita B, Saikia K. Formulation and evaluation of metronidazole microspheres loaded bio-adhesive vagina gel. Asian J Pharm Clin Res 2017;10:418-24.
14. Saritha T, Balaji A, Jaswanth A. Design and evaluation of forskolin buccal mucoadhesive microspheres. Int J Curr Pharm Res 2015;7:17-21.
15. Mohite PB, Khanage SG, Harischandre VS. Recent advances in micro-sponges drug delivery system. J Crit Rev 2016;3:9-16.
16. Rahman Z, Ali M, Khar RK. Design and evaluation of bi-layer floating tablets of captopril. Acta Pharm 2006;56:49-57.
17. Levis SR, Deasy P. Pharmaceutical applications of size reduced grades of surfactant co-processed microcrystalline cellulose. Int J Pharm 2001;23:25-33.
18. Chowdhary KPR, Rao YS. Mucoadhesive microcapsules of glipizide: characterization, in vitro and in vivo evaluation. Indian J Pharm Sci 2003;4:65-77.
19. Shovarani KN, Goundalkar AG. Preparation and evaluation of microsphere of diclofenac sodium. Indian J Pharm Sci 1994;56:45-50.
20. Tiwari SB, Murthy TK, Pai MR, Mehta PR, Chowdary PB. Controlled release formulation of tramadol hydrochloride using hydrophilic and hydrophobic matrix system. AAPS PharmSciTech 2003;4:1-6.
21. Phutane P, Shidhaye S, Lotlikar V, Ghule A. In vitro evaluation of novel sustained release microspheres of glipizide prepared by the emulsion solvent diffusion-evaporation method. J Young Pharm 2010;2:35-41.
22. Siepmann J, Peppas NA. Modelling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv Drug Delivery Rev 2001;48:139-57.
23. Obeidat WM, Price JC. Preparation and evaluation of Eudragit S 100 microspheres as pH-sensitive release preparations for piroxicam and theophylline using the emulsion-solvent evaporation method. J Microencapsul 2006;23:195-202.
24. Fattah DJ, Grant KE, Meshali MM. Physical characteristics and Release behavior of salbutamol sulfate beads prepared with different Ionic polysaccharides. Drug Dev Ind Pharm 1998;24:541-7.
25. Perumal D. Microencapsulation of ibuprofen and Eudragit RS 100 by the emulsion solvent diffusion technique. Int J Pharm 2001;218:1-11.
26. Gibaud S, Bonneville A, Astier A. Preparation of 3, 4-diaminopyridinemicroparticles by solvent-evaporation methods. Int J Pharm 2002;242:197-201.
27. Venkatesan P, Muralidharan C, Manavalan R, Valliappan K. Selection of a better method for the preparation of microspheres by applying analytic hierarchy process. J Pharm Sci Res 2009;1:64-78.
28. Kulkarni GT, Gowthamarajan K, Suresh B. Stability testing of pharmaceutical products: an overview. Indian J Pharm Educ 2004;38:194-202.
29. Albertini B, Passerini N, Sabatino MD, Vitali B, Brigidi P. Polymerâ€“lipid-based mucoadhesive microspheres prepared by spray-congealing for the vaginal delivery of econazole nitrate. Eur J Pharm Sci 2009;36:591-601.
30. Sanghvi SP, Nairn JG. Effect of viscosity and interfacial tension on particle size of cellulose acetate trimellitate microspheres. J Microencapsulation 1992;9:215-27.
31. Kilicarslan M, Baykara T. The effect of the drug/polymer ratio on the properties of the verapamil HCl loaded microspheres. Int J Pharm 2003;252:99-109.
32. Chou WH, Tsai TR, Hsu SH, Cham TM. Preparation and in vitro evaluation of nifedipine-loaded albumin microspheres cross-linked by different glutaraldehyde concentrations. Int J Pharm 1996;144:241-5.
33. Shabaraya AR, Narayanacharyulu R. Design and evaluation of chitosan microspheres of metoprolol tartrate for sustained release. Indian J Pharm Sci 2003;65:250-2.
34. Loyd A, Nicholas GP. Powders and granules. In: Kluwer W, William L. editors. Pharmaceutical dosage forms and drug delivery systems. 9th ed. New Delhi: Wilkins Press; 2011. p. 184-202.
35. Howard SA. Solid: flow properties. In: Swarbrick J. editor. Encyclopedia of Pharmaceutical Technology. 3rd ed. New York: Informa healthcare publication; 2006. p. 3275-96.
36. Velivela S, Abbulu K, Vinyas M, Pati NB. Formulation and in vitro evaluation of ritonavir floating tablets by melt granulation technique. Int J Appl Pharm 2016;8:12-5.
37. Sakhare SS, Yadav AV, Jadhav PD. Design, development and characterization of mucoadhesive gastro spheres of carvedilol. Int J Appl Pharm 2016;8:37-42.
38. Peppas NA. Analysis of fickian and non-fickian drug release from polymers. Pharm Acta Helv 1985;60:110â€“1.
39. Swain S, Meher D, Patra CN, Jammula S, Dinda SC. Design and characterization of sustained release mucoadhesive microspheres of tolterodine tartrate. Curr Drug Delivery 2013;10:413-26.