Stomach-specific drug delivery of 5-fluorouracil using floating alginate beads

Abstract

A multiple-unit-type oral floating dosage form (FDF) of 5-fluorouracil (5-FU) was developed to prolong gastric residence time, target stomach cancer, and increase drug bioavailability. The floating bead formulations were prepared by dispersing 5-FU together with calcium carbonate into a mixture of sodium alginate and hydroxypropyl methylcellulose solution and then dripping the dispersion into an acidified solution of calcium chloride. Calcium alginate beads were formed, as alginate undergoes ionotropic gelation by calcium ions and carbon dioxide develops from the reaction of carbonate salts with acid. The evolving gas permeated through the alginate matrix, leaving gas bubbles or pores, which provided the beads buoyancy. The prepared beads were evaluated for percent drug loading, drug entrapment efficiency, image, surface topography, buoyancy, and in vitro release. The formulations were optimized for different weight ratios of gas-forming agent and sodium alginate. The beads containing higher amounts of calcium carbonate demonstrated instantaneous, complete, and excellent floating ability over a period of 24 hours. The optimized formulation was subjected to in vivo antitumor studies to check the therapeutic efficacy of the floating dosage forms containing 5-FU against benzo(a)pyrene-induced stomach tumors in albino female mice (Balb/C strain). The multiple-bead FDF was found to reduce the tumor incidence in mice by 74%, while the conventional tablet dosage form reduced this incidence by only 25%. Results indicate that FDF performed significantly better than the simple tablet dosage form.

Development and evaluation of floating alginate microspheres for oral delivery of anthocyanins – A preliminary investigation

“…Unlike previous reports (Shishu, Gupta, & Aggarwal, ), the addition of CaCO 3 significantly increased the EE, especially for the microspheres gelled in cross‐linking bath containing 2% acetic acid (Figure ), which could indicate that the calcium ions released from the carbonate contributed to the internal gelation of the alginate chains.…”

“…The EE results reported in this study are lower than previously described by Nayak, Jain, and Pandey () (77.61–82.48%), Shishu et al. () (71.85–86.45%), and Singh, Deol, and Kaur () (74.37–75.0%), however significantly higher than those reported by Ma et al. () (19.49–20.12%).…”

Gastroretentive dosage forms: A review with special emphasis on floating drug delivery systems

“…Ionic gelation method, for preparation of floating beads (Whitehead et al, 1998;Talukder & Fassihi, 2004b, Pawar et al, 2008, was also adopted by a number of investigators. Different classes of pharmacotherapeutic agents were encapsulated in these systems, like anti-bacterial agent metronidazole (Murata et al, 2000;Sriamornsak et al, 2005;Ishak et al, 2007), anti-cancer agent like 5-fluorouracil (Shishu et al, 2007b), non-steroidal anti-inflammatory drug like piroxicam (Lee et al, 2001), anti-hypertensive agent like verapamil hydrochloride (Sawicki, 2002), and bronchodilator like theophylline (Yang et al, 2004). In a study (Gohel & Sarvaiya, 2007) it was revealed that gastroretentive tablets of rifampicin and isoniazid minimize the degradation of rifampicin and isoniazid in acidic medium because the developed system minimized the physical contact between the two drugs and also controlled release rifampicin in acidic medium.…”

Formulation and Evaluation of Alginate-Cellulose Floating Microspheres of Cefixime Trihydrate

“…The fully formed micro carriers were collected, washed with distilled water twice and subsequently air dried. 9,10,11 Floating alginate microspheres of cefixime with different types of co-polymers such as HPMC K4M, HPMCK 15M, and ethyl cellulose were prepared. The formulation details are given in Table 1, 2 & 3.…”