DEVELOPMENT AND EVALUATION OF CHRONOMODULATED DELIVERY SYSTEM OF METOCLOPRAMIDE HYDROCHLORIDE
Objective: Metoclopramide hydrochloride (meto) is indicated in the treatment of diabetic gastro paresis. It is also used in the treatment of pregnancy-induced morning sickness. Present work involved the development of a chrono-modulated delivery system of meto, intended to be taken at bedtime which would elicit the therapeutic response early in the morning when needed the most to prevent the symptoms of diabetic gastro paresis and morning sickness.
Methods: Immediate release tablets of meto were prepared and optimized for disintegration time and in vitro drug release. Subsequently, these tablets were compression coated using various ratios of glyceryl dibehenate and diluents. The resulting tablets were evaluated for disintegration time and in vitro drug release. Optimized formulation was subjected to accelerated stability studies for 3 mo.
Results: The optimized immediate release tablets exhibited disintegration time of 2-3 min and more than 90% drug release within 30 min. These tablets when compression coated with the optimized ratio of glyceryl dibehenate and di-calcium phosphate could delay the disintegration time to 251 min. In vitro release study of the tablets showed the lag phase of 4 h after which there was a complete drug release within 1 h. Accelerated stability studies indicated good physical and chemical stability of the formulation.
Conclusion: Chrono-modulated formulation of meto could delay the release of the drug by four h. This lag in the release is expected to modulate the time of therapeutic response of meto early in the morning at 6-7 h interval after the administration of dosage form at bedtime.
2. Center for drug evaluation and research, medical review: application no. 21-793. Applicant: Schwartz Pharma Inc; 2005.
3. Lee A, Kuo B. Metoclopramide in the treatment of diabetic gastroparesis. Expert Rev Endocrinol Metab 2010;5:653-62.
4. Patrick A, Epstein O. Review article: gastroparesis. Aliment Pharmacol Ther 2008;27:724-40.
5. Pastemak B, Svanstrom H, Melbye M, Hrild A. Metoclopramide in pregnancy and risk of major congenital malformations and fetal death. JAMA J Am Med Assoc 2013;16:1601-11.
6. Nargis M, Islam MS, Naushin F, Haider SS. Development of sustained release preparations of metoclopramide hydrochloride based on the fatty matrix. Dhaka Univ J Pharm Sci 2012;11:129-36.
7. El-Sayed YM, Niazy EM, Khidr SH. Preparation and in vitro evaluation of sustained release metoclopramide hydrochloride microspheres. J Microencapsul 1995;12:651-60.
8. Savaser A, Tas C, Bayrak Z, Ozkan CK. Effect of different polymers and their combinations on the release of metoclopramide hydrochloride from sustained release hydrophilic matrix tablets. Pharm Dev Technol 2013;18:1122-30.
9. Patel MH, Kumar PA, Kulkarni SV, Rao BS. Formulation and in vitro evaluation of controlled release matrix tablets of metoclopramide hydrochloride: influence of fillers on natural hydrophilic gums. Int J Pharm Pharm Sci 2012;4:181-7.
10. Raju S, Reddy PS, Kumar VA, Deepthi A, Reddy KS, Reddy PV. Flash release oral films of metoclopramide hydrochloride for pediatric use: formulation and in vitro evaluation. J Chem Pharm Res 2011;3:636-46.
11. Lakshmi AG, Patel R, Kumar DS. Formulation and evaluation of fast dissolving tablets of antiemetic drug metoclopramide. World J Pharm Pharm Sci 2014;3:2080-90.
12. Yadav DR, Ayyappan T, Shanmugma K, Sundermoorthy K, Vetrichelvan T. Development and in vitro evaluation of buccoadhesive metoclopramide hydrochloride tablet formulation. Int J Pharm Technol Res 2011;3:516-25.
13. Jindal S, Sharma A, Jindal K. Development of metoclopramide floating tablets based on HPMC matrices: a comparison study with the marketed formulation. Int J Pharm Teaching Practices 2015;5:2146-50.
14. Gangane PS, Mahajan NM, Danao KR, Pawde GN. Formulation and evaluation of a chronomodulated pulsatile therapeutic system for early morning surge in blood pressure. Int J Pharm Pharm Sci 2015;7:337-41.
15. Rajashree S, Masareddy MN, Gupta AL, Danish K. Development, and characterization of a diltiazem hydrochloride pulsatile drug delivery system for Chrono modulated therapy. Asian J Pharm Clin Res 2015;7:168-73.
16. Neeharika MS, Jyothi BJ. Chronotherapeutics: an optimizing approach to synchronize drug delivery with circardian rhythm. J Crit Rev 2015;2:31-40.
17. United States Pharmacopoeia. United States Pharmacopeial convention Inc. Rockville (MD) 2016;39:4847-48.
18. Aburahma MH, Badr-Eldin SM. Compritol 888ATO: a multifunctional lipid excipient in drug delivery systems and nanopharmaceuticals. Expert Opin Drug Delivery 2014;11:1865-83.
19. Patil S, Pund S, Joshi A. Chronomodulated press-coated pulsatile therapeutic system for aceclofenac: optimization of factors influencing drug release and lag time. Chronophysiol Ther 2011;1:1-10.