Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar,Mohali, Punjab-160 062, India, Institute of Biochemistry, Faculty of Medicine, Polytechnic University, Via Ranieri 67, IT-60100 Ancona, Italy,Green Biotechnology Research Group, The Special Division for Human Life Technology, National Institute of Advanced Industrial Science andTechnology, 1-8-31 Midorigaoka, Ikeda, Osaka-563-8577, Japan, and Department of Medicinal Chemistry & Natural Products,The Hebrew University of Jerusalem, School of Pharmacy-Faculty of Medicine, Jerusalem 91120, IsraelReceived March 2, 2004

Chitosan chemistry and pharmaceutical perspectives.

Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. For the treatment of human diseases, nasal and pulmonary routes of drug delivery are gaining increasing importance. These routes provide promising alternatives to parenteral drug delivery particularly for peptide and protein therapeutics. For this purpose, several drug delivery systems have been formulated and are being investigated for nasal and pulmonary delivery. These include liposomes, proliposomes, microspheres, gels, prodrugs, cyclodextrins, among others. Nanoparticles composed of biodegradable polymers show assurance in fulfilling the stringent requirements placed on these delivery systems, such as ability to be transferred into an aerosol, stability against forces generated during aerosolization, biocompatibility, targeting of specific sites or cell populations in the lung, release of the drug in a predetermined manner, and degradation within an acceptable period of time.

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Drug delivery systems: An updated review.

Polysaccharides in colon-specific drug delivery

Purpose. Although oral delivery has become a widely accepted route of administration of therapeutic drugs, the gastrointestinal tract presents several formidable barriers to drug delivery. Colonic drug delivery has gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon but also for its potential for the delivery of proteins and therapeutic peptides. To achieve successful colonic delivery, a drug needs to be protected from absorption and /or the environment of the upper gastrointestinal tract (GIT) and then be abruptly released into the proximal colon, which is considered the optimum site for colon-tar- geted delivery of drugs. Colon targeting is naturally of value for the topical treatment of diseases of colon such as Chron's diseases, ulcerative colitis, colorectal cancer and amebiasis. Peptides, proteins, oligonucleotides and vac- cines pose potential candidature for colon targeted drug delivery. Methods. The various strategies for targeting orally administered drugs to the colon include covalent linkage of a drug with a carrier, coating with pH-sensitive polymers, formulation of timed released systems, exploita- tion of carriers that are degraded specifically by colonic bacteria, bioadhesive systems and osmotic controlled drug delivery systems. Various prodrugs (sulfasalazine, ipsala- zine, balsalazine and olsalazine) have been developed that are aimed to deliver 5-amino salicylic acid (5-ASA) for localized chemotherapy of inflammatory bowl disease (IBD). Microbially degradable polymers especially azo crosslinked polymers have been investigated for use in tar- geting of drugs to colon. Certain plant polysaccharides such as amylose, inulin, pectin and guar gum remains unaf- fected in the presence of gastrointestinal enzymes and pave the way for the formulation of colon targeted drug delivery systems. The concept of using pH as a rigger to release a drug in the colon is based on the pH conditions that vary continuously down the gastrointestinal tract. Times dependent drug delivery systems have been devel- oped that are based on the principle to prevent release of drug until 3-4 h after leaving the stomach. Redox sensitive polymers and bioadhesive systems have also been exploited to deliver the drugs into the colon. Results. The approach that is based on the formation of prodrug involves covalent linkage between drug and carrier. The type of linkage that is formed between drug and carrier would decide the triggering mechanism for the release of drug in colon. The presence of azo reductase enzymes play pivotal role in the release of drug from azo bond prodrugs while glycosidase activity of the colonic microflora is responsible for liberation of drugs from glycosidic pro- drugs. Release of drugs from azo polymer coated dosage forms is supposed to take place after reduction and thus cleavage of the azo bonds by the azoreductase enzymes present in the colonic microflora. Natural polysaccharides have been used as tools to deliver the drugs specifically to the colon. These polysaccharides remain intact in the phys- iological environment of stomach and small intestine but once the dosage form enters into colon, it is acted upon by polysaccharidases, which degrades the polysaccharide and releases the drug into the vicinity of bioenvironment of colon. However, they should be protected while gaining entry into stomach and small intestine due to enormous swelling and hydrophilic properties of polysaccharides. This has been achieved either by chemical crosslinking or by addition of a protective coat. Formulation coated with enteric polymers releases drug when pH move towards alkaline range while as the multicoated formulation passes the stomach, the drug is released after a lag time of 3-5 h that is equivalent to small intestinal transit time. Drug coated with a bioadhesive polymer that selectively provides adhesion to the colonic mucosa may release drug in the colon. Conclusions. Improved drug delivery systems are required for drugs currently in use to treat localized dis- eases of the colon. The advantages of targeting drugs spe- cifically to the diseased colon are reduced incidence of systemic side effects, lower dose of drug, supply of the drug to the biophase only when it is required and mainte- nance of the drug in its intact form as close as possible to the target site.

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Pharmaceutical approaches to colon targeted drug delivery systems.

Spherical beads have been prepared by ionotropic gelation of sodium alginate in the presence of CaCl2 and BaCl2 solutions and their swelling behavior has been studied. The barium ion-crosslinked beads exhibit almost minimum swelling of 40 ± 3% in PBS at pH 7.4 but possess greater stability while calcium alginate beads exhibit nearly 160% of water uptake and subsequently dissolve. The beads appear to swell through ion-exchange process which was confirmed by monitoring the Ca2+ release from the calcium alginate beads. The release was found to be diffusion controlled. On treatment with 0.1 M HCl, the calcium alginate beads demonstrated a decrease in water uptake in PBS at pH 7.4 with faster degradation while for acid treated barium alginate beads, the water uptake was found to increase on treatment with HCl. When the two beads samples were put in media of continuous varying pH (to mimic the passage of beads from mouth to colon), barium alginate beads possessed greater stability, thus showing potential to be used for colon-targeted oral delivery.

Investigation of swelling/degradation behaviour of alginate beads crosslinked with Ca2+ and Ba2+ ions

In vitro evaluation of guar gum as a carrier for colon-specific drug delivery

Evaluation of guar gum as a compression coat for drug targeting to colon

Gamma scintigraphic studies on guar gum matrix tablets for colonic drug delivery in healthy human volunteers.

The aim of this study was to develop colon-specific delivery systems for 5-aminosalicylic acid (5-ASA) using guar gum as a carrier. Core tablets containing 5-ASA were prepared by wet granulation with starch paste and were compression coated with coating formulations containing different quantities of guar gum (300, 200, 150, and 125 mg). In vitro drug release studies were carried out in simulated gastric and intestinal fluids and in pH 6.8 buffer containing rat cecal contents. The application of 175 mg of coating formulation containing 150 mg of guar gum over 5-ASA core tablets resulted in the release of less than 2% drug in simulated gastric and intestinal fluids and about 93% of 5-ASA in pH 6.8 buffer containing rat cecal contents. Differential scanning calorimetric (DSC) studies showed the absence of any interaction between 5-ASA and the excipients on storage at 45°C for 12 weeks. The study confirmed that selective delivery of 5-ASA to the colon can be achieved using guar gum as a carrier in the form o...

Y.V Rama Prasad

Papers

In vitro evaluation of guar gum as a carrier for colon-specific drug delivery

Evaluation of guar gum as a compression coat for drug targeting to colon

Gamma scintigraphic studies on guar gum matrix tablets for colonic drug delivery in healthy human volunteers.

Studies of guar gum compression-coated 5-aminosalicylic acid tablets for colon-specific drug delivery.