Formulation and In Vitro Evaluation of Pellets Containing Sulfasalazine and Caffeine to Verify Ileo-Colonic Drug Delivery

The ColoPulse coating is a pH-dependent coating that can be used to target drug release to the ileo-colonic region. ColoPulse coated tablets and capsules have demonstrated their targeting capabilities in vivo in more than 100 volunteers and patients. However, so far the ColoPulse coating has not been used for multi-particulate pellet formulations. The sulfasalazine–caffeine method can be used to confirm ileo-colonic drug delivery in vivo. Caffeine serves as a release marker in this method, while sulfasalazine serves as a marker for colonic arrival. In this study, extrusion–spheronization was used to produce microcrystalline cellulose based pellets containing both caffeine and sulfasalazine. Dissolution tests revealed that a superdisintegrant, i.e., croscarmellose sodium or sodium starch glycolate, should be incorporated in the formulation to achieve acceptable release profiles for both sulfasalazine and caffeine. However, acceptable release profiles were only obtained when the pelletizing liquid consisted of ethanol/water 1/1 (v/v) but not with pure water. This phenomenon was ascribed to the differences in the degree of swelling of the superdisintegrant in the pelletizing liquid during the granulation process. The pellets were coated with the ColoPulse coating and showed the desired pH-dependent pulsatile release profile in vitro. In future clinical studies, ileo-colonic targeting should be verified.

Development of Personalized Colonic Drug Delivery Systems Prepared by 3D-Printing Technology

Colonic drug delivery systems (CDDS) show several advantages for treatment of inflammatory bowel disease such as improving the clinical outcomes and minimizing side effects of corticosteroids. However, variation of the patient's gastrointestinal tract (GIT) in terms of transit time and pH causes the fluctuation of the drug releasing site in the GIT resulting in low therapeutic efficiency. Consequently, 3D-printing techniques have been applied for preparation of personalized colonic drug delivery systems in this study. Prednisolone was selected as a model drug and prepared in the form of a core tablet. Polylactic acid (PLA) and polyvinyl alcohol (PVA) were printed as a tablet housing and a drug control release plug, respectively. A two-factor full factorial model was utilized to design the experiment and partial least square regression (PLS) models were generated to reveal and predict drug release time of the system. From the results, only thickness of the PVA plug significantly affected the drug release at sampling times of 5, 6, 10, and 24 h. The relations between thickness of the plug and drug releases at 5, 6, and 10 h are quadratic but that of 24 h is linear. The relation between thickness of the plug and drug releases is quadratic. The drug could not be completely released in 24 h because the drug was entrapped by PVA gel. The search results show the possibility to utilize the PLS models to modify drug release time for individual patients. However, alteration of plug polymer is a suggestion to obtain complete drug release.

Potential application of Colonic drug delivery system in prevention and treatment of Colorectal Cancer

Colorectal cancer (CRC) is the second leading cause of cancer related deaths in USA. The current regimen used to treat colorectal cancer has many side effects and have higher drug distribution in other tissues. Physical activity and diet play major role in prevention of Colon cancer which is briefly discussed in this paper. Colon targeted drug delivery system (CoDDS) is found to be a promising approach to target the drug specifically to colon. This review provides the description of various colon targeted approaches that can be used to treat CRC. Factors to be consider while designing CoDDS include pH of GIT, Transit time of GI tract and Microbiota of colon. This review will discuss the staging and standard treatments modalities for CRC.

New Insights of Oral Colonic Drug Delivery Systems for Inflammatory Bowel Disease Therapy

Colonic Drug Delivery Systems (CDDS) are especially advantageous for local treatment of inflammatory bowel diseases (IBD). Site-targeted drug release allows to obtain a high drug concentration in injured tissues and less systemic adverse effects, as consequence of less/null drug absorption in small intestine. This review focused on the reported contributions in the last four years to improve the effectiveness of treatments of inflammatory bowel diseases. The work concludes that there has been an increase in the development of CDDS in which pH, specific enzymes, reactive oxygen species (ROS), or a combination of all of these triggers the release. These delivery systems demonstrated a therapeutic improvement with fewer adverse effects. Future perspectives to the treatment of this disease include the elucidation of molecular basis of IBD diseases in order to design more specific treatments, and the performance of more in vivo assays to validate the specificity and stability of the obtained systems.

Progestogens Are Metabolized by the Gut Microbiota: Implications for Colonic Drug Delivery

Following oral administration, the bioavailability of progestogens is very low and highly variable, in part due to metabolism by cytochrome P450 enzymes found in the mucosa of the small intestine. Conversely, the mucosa in the colon contains much lower levels of cytochrome P450 enzymes, thus, colonic delivery of progestogens may be beneficial. Microbiota in the colon are known to metabolize a great number of drugs, therefore, it is important to understand the stability of these hormones in the presence of colonic flora before developing formulations. The aim of this study was to investigate the stability of three progestogens: progesterone, and its two synthetic analogues, medroxyprogesterone acetate (MPA) and levonorgestrel (LNG), in the presence of human colonic microbiota. Progesterone, MPA, and LNG were incubated in mixed fecal inoculum (simulated human colonic fluid) under anerobic conditions. Progesterone was completely degraded after 2 h, whereas levels of MPA and LNG were still detectable after 24 h. The half-lives of progesterone, MPA, and LNG in fecal inoculum were 28, 644, and 240 min, respectively. This study describes the kinetics of colonic microbial metabolism of these hormones for the first time. MPA and LNG show promise for delivery to the colon, potentially improving pharmacokinetics over current oral delivery methods.

Cubic Microcontainers Improve In Situ Colonic Mucoadhesion and Absorption of Amoxicillin in Rats

An increased interest in colonic drug delivery has led to a higher focus on the design of delivery devices targeting this part of the gastrointestinal tract. Microcontainers have previously facilitated an increase in oral bioavailability of drugs. The surface texture and shape of microcontainers have proven to influence the mucoadhesion ex vivo. In the present work, these findings were further investigated using an in situ closed-loop perfusion technique in the rat colon, which allowed for simultaneous evaluation of mucoadhesion of the microcontainers as well as drug absorption. Cylindrical, triangular and cubic microcontainers, with the same exterior surface area, were evaluated based on in vitro release, in situ mucoadhesion and in situ absorption of amoxicillin. Additionally, the mucoadhesion of empty cylindrical microcontainers with and without pillars on the top surface was investigated. From the microscopy analysis of the colon sections after the in situ study, it was evident that a significantly higher percentage of cubic microcontainers than cylindrical microcontainers adhered to the intestinal mucus. Furthermore, the absorption rate constants and blood samples indicated that amoxicillin in cubic microcontainers was absorbed more readily than when cylindrical or triangular microcontainers were dosed. This could be due to a higher degree of mucoadhesion for these particular microcontainers.