FORMULATION OPTIMIZATION OF PROMETHAZINE THEOCLATE IMMEDIATE RELEASE PELLETS BY USING EXTRUSION-SPHERONIZATION TECHNIQUE
Objective: Promethazine theoclate is a BCS Class II drug having anti-histaminic property and mainly used for the treatment of motion sickness and postoperative emesis. The main objective of the research work was to formulate and optimize immediate release pellets of promethazine theoclate by using the extrusion-spheronization technique to offer immediate release dosage form suitable for treatment of nausea and vomiting associated with motion sickness and post-operative conditions.
Methods: Immediate release pellets of promethazine theoclate were prepared by using microcrystalline cellulose (MCC) and corn starch as filler and disintegrant respectively along with other excipients. Pellet formulation was further optimized for bulk density, disintegration time and percent drug release after 10 min. using 32 factorial design. Formulations were also characterized for drug-polymer interactions using Differential Scanning Calorimetry (DSC), surface morphology by Scanning Electron Microscopy (SEM) and other physicochemical properties.
Results: Optimised pellet formulation contains 2.5:4.5:1 ratio of MCC: Corn Starch: Drug and spheronization time of 60 seconds showing highest percent yield of 78% and immediate drug release of 100.52Â±0.65% after 10 min.
Conclusion: Promethazine theoclate pellets formulated in this study can serve as an alternative to tablet dosage form which can give immediate drug release for treatment of motion sickness and postoperative emesis.
2. Kumar P, Tiwari A, Chhabra Gand, Pathak K. Use of central composite design for statistical optimization promethazine theoclate loaded solid lipid nanoparticles. Asian J Pharm 2014;8:279-86.
3. Vats SK, Gupta RN, Kalaiselvan R, Singh R. Design and statistical evaluation of a multiunit delivery system containing nisoldipine-soluplusÂ® solid dispersion for hypertension chronotherapy. Int J Pharm Sci 2016;10:170-7.
4. Sharma S, Sharma N, Gupta G. Formulation of fast-dissolving tablets of promethazine theoclate. Trop J Pharm Res 2010;9:489â€“97.
5. Latha S, Selvamani P, Thirunavukkarasu C, Pal TK, Ghosh LK. Development and comparative evaluation of a trans dermal therapeutic system for antiemetic therapy. Asian J Chem 2011;23:5267-70.
6. Cantisani C, Ricci S, Grieco T, Paolino G, Faina V, Silvestri E. Topical promethazine side effects: our experience and review of the literature. BioMed Res Int 2013;9. http://dx.doi. org/10.1155/2013/151509
7. Nalanda TR, Prashant KP. Development of multiparticulate formulation and evaluation of colon targeted drug delivery system of ciprofloxacin: in vivo study with induced colitis model in rats. Asian J Pharm Clin Res 2017;10:167-85.
8. Doniparthi B, Jeevana J. multiparticulate drug delivery systems using natural polymers as release retardant materials. Int J Pharm Pharm Sci 2014;6:61-5.
9. Tomer G, Patel H, Podczeck F, Newton JM. Measuring the water retention capacities (MRC) of different microcrystalline cellulose grades. Eur J Pharm Sci 2001;12:321-5.
10. Rahman MA, Ahuja A, Baboota S, Bali V, Saigal N, Ali J. Recent advances in pelletization technique for oral drug delivery: a review. Curr Drug Delivery 2009;6:122-9.
11. Oâ€™Connor RE, Schwartz JB. Spheronization II: drug release from drug-diluent mixtures. Drug Dev Ind Pharm 1985;11:1837â€“57.
12. Okada S, Nakahara H, Isaka H. Adsorption of drugs on microcrystalline cellulose suspended in aqueous solutions. Chem Pharm Bull 1987;35:761â€“8.
13. Rivera SL, Ghodbane S. In vitro adsorption-desorption of famotidine on microcrystalline cellulose. Int J Pharm 1994;108:31â€“8.
14. Otero-Espinar FJ, Luzaro-Alvarez A, Blanco-Mendez J. Non-MCC materials as extrusion-spheronization aids in pellets production. J Drug Delivery Sci Technol 2010;20:303-18.
15. Cherian C, Arnepalli D, Dogga N, Raviteja NB, Gorie SV. Assessment of grain size and pore size distribution using digital image analysis: proceedings of indian geotechnical conference IGC, Indian Institute of Technology Madras, Kakinada India; 2014.
16. Chamsai B, Pornsak S. Novel disintegrating microcrystalline cellulose pellets with improved drug dissolution performance. Powder Technol 2013;233:278-85.
17. Gregory T, Fabrice K, Bruno L, Brian C, Brigitte E. Microcrystalline cellulose, a direct compression binder in a quality by design environment-a review. Int J Pharm 2014;473:64-72.
18. Parind MD, Celine VL, Paul WSH. Review of disintegrants and the disintegration Phenomena. J Pharm Sci 2016;105:2545-55.