Journal of Microencapsulation, 2012; 29(1): 72–82 ß 2012 Informa UK Ltd. ISSN 0265-2048 print/ISSN 1464-5246 online DOI: 10.3109/02652048.2011.629789 A novel hydrogel plug of Sterculia urens for pulsatile delivery: in vitro and in vivo evaluation Jitendra R. Amrutkar 1 and Surendra G. Gattani 2 1 Formulation and Development, Dr. Reddy’s Laboratories Limited, Ranga Reddy District 500 072, Andhra Pradesh, India, and 2 Department of Pharmaceutics, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425 405, Maharashtra, India Abstract The objective of this study was to investigate a novel hydrogel plug using isolated root mucilage of Sterculia urens to obtain a desired lag time for an oral chronotherapeutic colon-specific pulsatile drug delivery of indomethacin. Pulsatile drug delivery was developed using chemically treated hard gelatin capsule bodies filled with eudragit multiparticulates of indomethacin, and sealed with different hydrogel plugs (root mucilage of S. urens, xanthan gum, guar gum, HPMC K4M and combination of maltodextrin with guar gum). Indomethacin multiparticulates were prepared using extrusion spheronization, spray drying and solvent evaporation techniques with Eudragit Õ L-100 and S-100 (1:2) by varying drug-to-polymer ratio. After oral administration, the water-soluble cap of capsule dissolved in the intestinal fluid and the hydrogel plug swells. After a controlled time, the swollen plug subsequently ejected from the dosage form, releases the contents of the capsule. The formulation factors affecting the drug release were concentration and types of hydrogel plug used. In vivo gamma scintigraphy study in healthy rabbits proved the capability of the system to release drug in lower parts of the gastrointestinal tract after a programmed lag time. This study demonstrates that the indomethacin multiparticulates could be successfully colon-targeted by the design of time and pH-dependent modified chronopharmaceutical formulation. In conclusion, the investigated novel hydrogel plug could be a valuable tool for achieving desired lag time. Keywords: Sterculia urens, mucilage, hydrogel plug, colon specific, pulsatile, indomethacin, gamma scintigraphy Introduction Colon-specific drug delivery system (CDDS) has been developed as a site-specific drug delivery system. Along with many applications in local and systemic delivery of drugs, the CDDS would also be advantageous when a delay in absorption is desirable from a therapeutic point of view to treat diseases that have peak symptoms in the early morning and that exhibit circadian rhythm, such as nocturnal asthma, angina and rheumatoid arthritis (Bi Botti, 2004; Sarasija and Stutie, 2005). Developing the pulsatile device for colon-specific delivery offers some advantages such as: plasma peak is obtained at an optimal time, number of doses per day can be reduced, saturable first-pass metabolism and tolerance development can also be avoided (Martin and Banks-Schlegel, 1998; Morta et al., 1998; Gwen, 2002). There were currently few strategies to achieve colon specificity such as bacterially triggered, pressure-controlled, pH- and time-dependent CDDS (Yang et al., 2002; Chourasia and Jain, 2003). Multiparticulate dosage form such as matrix or coated pellets and granules, minitablets or microparticles (micro- capsules or microspheres) have gained interests in oral- sustained release formulations. Multiparticulates can be filled into capsule, after the capsules dissolves; multiparti- culate will be widely dispersed throughout the gastrointes- tinal tract (GIT) (Kramer and Blume, 1994). The main advantage of a multiparticulate dosage form relating to its Address for correspondence: Jitendra R. Amrutkar, Formulation and Development, IPDO, Innovation Plaza, Dr. Reddy’s Laboratories Limited, Ranga Reddy District 500 072, Andhra Pradesh, India. Tel: +912592 221627. Mobile: þ918106542107. Fax: +912592 221919. E-mail: jeetpharma7@rediffmail.com; jitendrara@drreddys.com (Received 31 Jan 2011; accepted 19 Sep 2011) http://www.informahealthcare.com/mnc 72 (Received 31 Jan 2011; accepted 19 Sep 2011) http://www.informahealthcare.com/mnc 72 Journal of Microencapsulation Downloaded from informahealthcare.com by Ondokuz Mayis Univ. on 11/07/14 For personal use only.