Research Journal of Pharmacy and Technology

Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Formulation and Evaluations of Methotrexate Loaded Multiparticulate System for Colon Targeting:In vitro and Surface Morphology


Affiliations
1 Pharmaceutics Research Division, Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, (A Central University), Bilaspur C.G-495009, India
     

   Subscribe/Renew Journal


Present study was investigated to prepare and evaluate multiparticulate system based microspheres of methotrexate (MTX) for the purpose of targeting to colonic region, reduce dosing frequency and improve patient compliances. In the present study we have used emulsifying agent and polymer (Eudragit S100) by solvent evaporation method, Polymer concentration and steering speed was used to formulate the microspheres by emulsion solvent evaporation technique. The particle size, shape, and surface morphology were investigated for prepared formulation. Further the percentage yield, DSC, XRD and in vitro drug release behavior were studied. The findings of particle size, surface morphology, entrapment efficiency and %yield of prepared microsphere were appreciable. The release study was done in simulated gastrointestinal fluids for 2 hrs in SGF (pH 1.2), for 3 hrs in SIF (pH 6.8) and up to 14 hrs in SCF (pH 7.4) and have shown that the drug was protected from being released in the physiological environment of the stomach and small intestine and efficiently released in colon. Among all the formulations it was observed that R2 value of formulation SS 3b was more near to one than other formulations. On the basis of this parameter, SS 3b was selected for further study. It is concluded from the present study that pH sensitive Eudragit microspheres are promising carriers for oral colon-targeted delivery of MTX for treatment of colorectal cancer.

Keywords

Methotrexate, Microspheres, Emulsifying Agent, Eudragit S-100, Colon Targeting, Colorectal Cancer.
Subscription Login to verify subscription
User
Notifications
Font Size


  • Al-Hashimi N , Begg N , Alany RG , Hassanin H , Elshaer A . Oral Modified Release Multiple-Unit Particulate Systems: Compressed Pellets, Microparticles and Nanoparticles.Pharmaceutics. 2018; 4: 10-14.

  • Jose et al., Indian journal of pharmaceutical sciences, 2010; 1: 58-64.

  • Rajeev Garg, GD Gupta. Development and Characterization of Cellulose and Eudragit Gastroretentive Floating Microspheres of Acyclovir. Research J. Pharm. and Tech. 2(1): Jan.-Mar. 2009; Page 101-105.

  • Mukund G Tawar, PD Chaudhari. Design and Dissolution Study of Colon Specific Drug Delivery System of Tinidazole. Research J. Pharm. and Tech.2 (4): Oct.-Dec. 2009; Page 862-864.

  • World Cancer Research Fund International, in: C.c Statistics (Ed.), 2012.

  • Mahmoudi M., Sant S., Wang B., Laurent S., Sen T., Superparamagnetic iron oxide nanoparticles (SPIONs): development, surface modifcation and applications in chemotherapy,Adv. Drug Deliv. Rev., 2011; 63: 24–46.

  • Dheeraj Ahirwar, Bharti Ahirwar, Anish Chandy. Microspheres for Targeting an Alkaloidal Anticancer Drug in Colon Cancer. Research J. Pharm. and Tech 6(6): June 2013; Page 618-621

  • J.K. Oh, J.M. Park, Iron oxide-based superparamagnetic polymeric nanomaterials: design, preparation, and biomedical application, Prog. Polym. Sci., 2011; 36: 168–189.

  • Agrawal D, Ranawat M.S., Chauhan C.S., Kamble R., formulation and charecterisation of colon targeted ph dependent microspheres of capecitabine for colorectal cancer, Journal of Drug Delivery & Therapeutics,2013; 3(6): 215-222

  • Bhardwaj J. and Mukhopadhyay S.,design and evaluation of methotrexate loaded multilayered tablet formulation for treatment of colon cancer, IJPSR 2014; 5:4-5.

  • Dupuis, C., Mercier, C., Yang, C, Monjanel-Mouterde, S., Ciccolini, J., Fanciullino, R., et al.; High-dose methotrexate in adults with osteosarcoma: a population pharmacokinetics study and validation of a new limited sampling strategy; Anticancer Drugs, 2008; 19:267–273.

  • Zelcer, S., Kellick, M., Wexler, L.H., Gorlick, R., Meyers, P.A.; The Memorial Sloan Kettering Cancer Center experience with outpatient administration of high dose methotrexate with leucovorin rescue; Pediatric Blood and Cancer, 2008; 50: 1176–1180.

  • Chla´dek, J., Grim, J., Martı´nkova J., Simkova M., Vanı`e`kova J., Koudelkova V., et al.; Pharmacokinetics and pharmacodynamics of low-dose methotrexate in the treatment of psoriasis; British Journal of Clinical Pharmacology, 2002; 54: 147–156.

  • A. Hajare, Y. T. Shetty. Formulation, Characterization and In-Vitro Evaluation of Floating Microspheres of Diltiazem Hydrochloride by Ionotropic Gelation technique. Research J. Pharm. and Tech. 1(1): Jan.-Mar. 2008; Page 52-56.

  • Radhika PR, Luqman Moidutty, Borkhataria Chetan H. Preparation and Evaluation of Delayed Release Aceclofenac Microspheres. Research J. Pharm. and Tech. 1(3): July-Sept.. 2008;Page 270-272

  • Stamp, L., Roberts, R., Kennedy, M., Barclay, M., O’Donnell, J.,Chapman, P.; The use of low dose methotrexate in rheumatoid arthritis— Are we entering a new era of therapeutic drug monitoring and pharmacogenomics? Biomedicine and Pharmacotherapy, 2006; 60: 678–687.

  • Inamoto, Y., Flowers, M.E., Appelbaum, F.R., Carpenter, P.A., Deeg, H.J., Furlong, T., et al.; A retrospective comparison of tacrolimus versus cyclosporine with methotrexate for immunosuppression after allogeneic hematopoietic cell transplantation with mobilized blood cells; Biology of Blood and Marrow Transplantation, 2011; 17: 1088–1192.

  • Chourasia M.K.,.Jain S.K, “Pharmaceutical Approaches to Colon Targeted Drug Delivery System”J Pharm Pharmacet Sci, 2003;6(1):33-66

  • Sharma A., Jain K Amit, “Colon Targeted Drug Delivery Using Different Approaches” IJPSR,2010;1(1):60-66

  • El-Kamel A.H., Sokar M.S., Al Gamal S.S., Naggar V.F., “Preparation And Evaluation Of Ketoprofen Floating Oral Delivery System” International Journal of Pharmaceutics , 2001;220:13 – 21

  • Jameel Ahmed Mulla, Sarasija Suresh, Imtiyaz Ahmed Khazi. Formulation, Characterization and in vitro Evaluation of Methotrexate Solid Lipid Nanoparticles. Research J. Pharm. and Tech.2 (4): Oct.-Dec. 2009; Page 685-689.

  • Zahirul M., Khan I., Prebeg Z.,Kurjakovic N., “A pH-dependent colon targeted oral drug delivery system using methacrylic acid copolymers” Journal of Controlled Release, 1999;58: 215–222

  • British Pharmacopoeia Her Majestry stationary office London 1993 1:227

  • Indian Pharmacopoeia, 1996 Government of India ministry of health and family welfare publishedController of Publications in Delhi . volume 1, A 146.

  • Marwa H., Omaima A., Hanaa A. El-ghamry., Hanan M. El-nahas and Waleed Barakat Development and Characterization of Controlled Release Ketoprofen Microspheres Journal of Applied Pharmaceutical Science, 2012 ; 02: 60-67.

  • A.G. Chintale, V.S. Kadam, K.S. Maske, D.B. Raut, S.V. Kale, S.D. Rai. Recent Advances in Microsphere Drug Delivery System: A Review. Research J. Pharm. and Tech. 6(3): March 2013; Page 307-312.

  • Anand Patel, C. C. Patil, R. V. Kulkarni, Vijaykumar A, Prashant Jorapur, Akshay Deshpande, Swapna W. Development and Evaluation of Sustain Release Pioglitazone Microsphere. Research J. Pharm. and Tech 2018; 11(12): 5348-5354.

  • Ashish Y. Pawar, Rahul A. Ahirrao. Formulation and Evaluation of Colon Targeted Drug Delivery System of Mesalamine Using Wet Granulation. Research J. Pharm. and Tech. 7(11): Nov. 2014 Page 1270-1279.

  • M. Purushothaman, Sowjanya Battu, K. Jyothshna Devi, C. Madhusudhana Chetty, M. Alagusundaram, K. Mallikarjuna Rao. Formulation and Characterization of Ofloxacin Microspheres Prepared By Ionotropic Gelation Technique. Research J. Pharm. and Tech.3 (4): Oct.-Dec.2010; Page 1265-1269.

  • Phalguna Yadagiri, Rama Rao Korapati. Formulation, Characterization and In Vitro Evaluation of Lamivudine Microspheres. Asian J. Res. Pharm. Sci. 2016; 6(4): 235-239.

  • Nayak A, Pal D., Formulation optimization and evaluation of jackfruit seed starch–alginate mucoadhesive beads of metformin HCl., International Journal of Biological Macromolecules, 2013: 59; 264– 272

  • Nighute A B, Bhise S B. Preparation and Evaluation of Microspheres of Rifabutin using Eudragit Polymers. Research J. Pharm. and Tech.2 (4): Oct.-Dec. 2009; Page 680-684.


Abstract Views: 280

PDF Views: 0




  • Formulation and Evaluations of Methotrexate Loaded Multiparticulate System for Colon Targeting:In vitro and Surface Morphology

Abstract Views: 280  |  PDF Views: 0

Authors

Sandeep Kumar Sonkar
Pharmaceutics Research Division, Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, (A Central University), Bilaspur C.G-495009, India
S. K. Lanjhiyana
Pharmaceutics Research Division, Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, (A Central University), Bilaspur C.G-495009, India

Abstract


Present study was investigated to prepare and evaluate multiparticulate system based microspheres of methotrexate (MTX) for the purpose of targeting to colonic region, reduce dosing frequency and improve patient compliances. In the present study we have used emulsifying agent and polymer (Eudragit S100) by solvent evaporation method, Polymer concentration and steering speed was used to formulate the microspheres by emulsion solvent evaporation technique. The particle size, shape, and surface morphology were investigated for prepared formulation. Further the percentage yield, DSC, XRD and in vitro drug release behavior were studied. The findings of particle size, surface morphology, entrapment efficiency and %yield of prepared microsphere were appreciable. The release study was done in simulated gastrointestinal fluids for 2 hrs in SGF (pH 1.2), for 3 hrs in SIF (pH 6.8) and up to 14 hrs in SCF (pH 7.4) and have shown that the drug was protected from being released in the physiological environment of the stomach and small intestine and efficiently released in colon. Among all the formulations it was observed that R2 value of formulation SS 3b was more near to one than other formulations. On the basis of this parameter, SS 3b was selected for further study. It is concluded from the present study that pH sensitive Eudragit microspheres are promising carriers for oral colon-targeted delivery of MTX for treatment of colorectal cancer.

Keywords


Methotrexate, Microspheres, Emulsifying Agent, Eudragit S-100, Colon Targeting, Colorectal Cancer.

References