The Effect of Thermal-Treating on Drug Release from Sustained Release Alginate-Eudragit RS Matrices.

Purpose: The main objective of the present study was to develop the colonic delivery system for 5-aminosalicylic acid (5-ASA) as an anti-inflammatory drug. Methods: Matrix pellets containing various proportions of alginate, calcium and Eudragit® RS were prepared by extrusion-spheronization technique. Thermal treatment was used to investigate the effect of the curing process on the surface morphology, mechanical and physicochemical properties and in vitro drug release profile of pellets. Based on the obtained results optimal formulations were selected to coating by the Eudragit® RS and subjected to a subsequent continuous dissolution test. Results: Image analysis and also scanning electron microscopy results proved acceptable morphology of the pellets. The fourier transform infrared spectroscopy and differential scanning calorimetry studies ruled out any interactions between the formulation's components. Curing process did not alter the mechanical properties of pellets. The release rate of the drug from matrices was prolonged due to the decreased porosity of cured pellets. Furthermore, selected cured pellets which coated with Eudragit® RS, prevented undesired premature drug release. Conclusion: Formulation containing 17.5% calcium, 17.5% alginate, and a coating level of 10% demonstrated enhanced drug release so that provided resistance to acidic conditions, allowing complete drug release in alkaline pH, mimicking colonic environment. The slow and consistent drug release from this formulation could be used for treatment of a broader range of Inflammatory bowel disease (IBD) patients especially in whom colonic pH levels have been measured at lower than pH 7.0.

Naringenin Nano-Delivery Systems and Their Therapeutic Applications.

Naringenin (NRG) is a polyphenolic phytochemical belonging to the class of flavanones and is widely distributed in citrus fruits and some other fruits such as bergamot, tomatoes, cocoa, and cherries. NRG presents several interesting pharmacological properties, such as anti-cancer, anti-oxidant, and anti-inflammatory activities. However, the therapeutic potential of NRG is hampered due to its hydrophobic nature, which leads to poor bioavailability. Here, we review a wide range of nanocarriers that have been used as delivery systems for NRG, including polymeric nanoparticles, micelles, liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), nanosuspensions, and nanoemulsions. These nanomedicine formulations of NRG have been applied as a potential treatment for several diseases, using a wide range of in vitro, ex vivo, and in vivo models and different routes of administration. From this review, it can be concluded that NRG is a potential therapeutic option for the treatment of various diseases such as cancer, neurological disorders, liver diseases, ocular disorders, inflammatory diseases, skin diseases, and diabetes when formulated in the appropriate nanocarriers.

Synthesis of a novel PEGylated colon-specific azo-based 4- aminosalicylic acid prodrug.

OBJECTIVES: 4-aminosalicylic acid (4-ASA) is an isomer of mesalazine that has recently been shown to be effective against inflammatory bowel disease (IBD), and more specifically, ulcerative colitis. However, the majority of orally administered 4-ASA is readily and extensively absorbed from the stomach and small intestine, so only a small amount is transported to the colon. A mutual ester and azo prodrug of 4-ASA was synthesized with polyethylene glycol (PEG) and dimethylaniline, respectively , to overcome this issue. MATERIALS AND METHODS: The 4-ASA prodrug was synthesized via a two-step process and then characterized by 1H-NMR. The stability of the prodrug was evaluated in simulated gastric fluid (pH 1.2). Furthermore, the in vitro release profiles of the drug conjugate was evaluated at pH 1.2, as well as pH 6.8 in the absence or presence of rat cecal content. RESULTS: The prepared prodrug was stable at pH 1.2, indicating that it could be protected from the acidic environment of the stomach. Also, the results of drug release at pH 6.8 showed that the amount of 4-ASA released was 63% within 12 hr in the absence of rat cecal content, while in the presence of rat cecal content, 97% of 4-ASA was released from the prodrug in 6 hr. CONCLUSION: Overall, the synthesized PEGylated azo-based 4-ASA prodrug could be a potential candidate for targeted drug delivery to the inflamed gut tissue in IBD.

A review on 5-aminosalicylic acid colon-targeted oral drug delivery systems.

Site-specific colon drug delivery is a practical approach for the treatment of local diseases of the colon with several advantages such as rapid onset of action and reduction of the dosage of the drug as well as minimization of harmful side effects. 5-aminosalicylic acid (5-ASA) is a drug of choice in the treatment of inflammatory bowel disease and colitis. For the efficient delivery of this drug, it is vital to prevent 5-ASA release in the upper part of the gastrointestinal tract and to promote its release in the proximal colon. Different approaches including chemical manipulation of drug molecule for production of prodrugs or modification of drug delivery systems using pH-dependent, time-dependent and/or bacterially biodegradable materials have been tried to optimize 5-ASA delivery to the colon. In the current review, the different strategies utilized in the design and development of an oral colonic delivery dosage form of 5-ASA are presented and discussed.

Investigation of using pectin and chitosan as natural excipients in pellet formulation.

This study aimed to evaluate the potential of applying pectin and chitosan polysaccharides in pellet formulation. These biopolymers have advantages such as biocompatibility, low toxicity, low price and easy processing which make them interesting candidates for drug delivery purposes. Careful control of pellet porosity is essential to achieve an appropriate drug release profile. Replacing microcrystalline cellulose (MCC) with polysaccharides, especially pectin, leads to increased pellet porosity. Theophylline, dimenhydrinate and ibuprofen were chosen as model drugs. Investigation of possible ionic interactions between drugs and excipients is crucial to optimize the formulation of pellets with acceptable drug release. Differential scanning calorimetry of chitosan showed an endothermic peak; however, this peak was not observed in thermograms of the pectin, implying the lack of interaction between polysaccharides. Fourier transform infrared analysis did not indicate any interaction between drugs and polymers. Incorporation of MCC into the pellet formulation significantly increased the mean dissolution time while substitution of MCC with polysaccharides led to a faster release for each of the three drugs - that were different in their net charges - in both acidic and buffer media. These results highlight the potential value of polysaccharides in improving drug delivery characteristics of pharmaceutical pellets.