Colonic pressure controlled

Recently, Yoshikawa et al. [70] reported a new in vitro dissolution test, called the rotating beads method, for drugs formulated in pressure-controlled colon delivery capsules. This dissolution method was applied to acetominophen sustained-release tablets and two other drugs having low solubility in the colon, tegafur and 5-ASA. There was good correlation between the in vitro dissolution rates and the in vivo absorption rates. 

Yoshikawa, Y., Hu, Z., Kimura, G., Muranishi, M., Yoshikawa, H., and Takada, K., A dissolution test for a pressure-controlled colon delivery capsule rotating beads method, J. Pharm. 

Pressure-controlled Disintegration of the drug release dosage form in the colon... 

Another strategy rehes on the strong peristaltic waves in the colon that lead to a temporarily increased luminal pressure (pressure-controlled drug release). Pressure-sensitive drug formulations release the drug as soon as a certain pressure limit is attained, i.e. destruction force is exceeded. 

A unique idea is the use of a pressure-controlled capsule in colonic targeting. The inner surface of this capsule is coated with ethylcellulose. Capsules prepared in this way do not disintegrate in the stomach and small intestine but... 

T. Takaya, K. Niwa, K. Matsuda, N. Danno, and K. Takada, Evaluation of pressure-controlled colon delivery capsule made of ethylcellulose, Proceed. Intern. Symp. Control. Rel. Bioact. Mater. 23 603-604 (1996). 

Among newly developed colon-specific drug delivery systems, pressure-controlled delivery capsules (PCDCs) [161] can be mentioned. Their mechanism of action is based on the relatively strong peristaltic waves taking place in the colon and leading to an increased luminal pressure. They consist of a capsular-shaped suppositories coated with a water-insoluble polymer (ethyl cellulose). Once taken orally, PCDCs behave like an ethyl cellulose balloon, because the suppository base liquefies at body temperature. In the upper GI tract, PCDCs are not directly subjected to the luminal pressures since sufficient fluid is present in the stomach and small intestine. The reabsorption of water in the colon provokes an increase of the luminal content viscosity. As a result, increased intestinal pressures directly affect the system via colonic peristalsis. Consequently, PCDCs mpture and drug release in the colon take place. 

Shibata N, Obno T, Shimokawa T, Hu Z, Yoshikawa Y, Koga K, Murakami M, and Takada K. Application of pressure-controlled colon delivery capsule to oral administration of glycyrrhizin in dogs. J. Pharm. Pharmacol. 2001 53 441-447. 

Pressure-controlled systems. These systems rely on the strong peristaltic waves in the colon that temporarily increase the luminal pressure. 

Jeong YI, Ohno T, Hu Z, et al. Evaluation of an intestinal pressure-controlled colon delivery capsule prepared by dipping method. J Control Release 2001 71 175-182. 

Figure 33-3. Summary of the renin-angiotensin-aldosterone system. Aldosterone secretion is controlled by several factors, including increased K+,ACTH, or angiotensin II.A1-dosterone acts to increase Na+ retention by both the kidney and colon.Aldosterone also promotes renal K+ excretion, which contributes to maintenance of Na+/K+ balance. In the absence of aldosterone, Na+ is lost, K+ is enhanced, the extracellular fluid volume is reduced, and mean arterial pressure and renal perfusion pressure are decreased. As a result, renin secretion is increased, leading to increased formation of angiotensin II, which promotes vasoconstriction and aldosterone secretion.

Symptomatic diverticular disease often responds to an increase in dietary fibre, and addition of a stool bulking agent. Antispasmodic drugs are helpful in controlling the pain of colon spasm but antimotility drugs encourage stasis of bowel contents, increase intracolonic pressure, and should be avoided. Diverticulitis requires treatment with broad spectrum antimicrobials for 7-10 days (e.g. 

There are several contraindications for TIPS absolute contraindications consist of right-sided heart failure with elevated central venous pressure, polycystic liver disease, and severe hepatic failure (Shiffman et al. 1995). The latter contraindication is based on the fact that the TIPS shunts blood away from the liver, thus further compromising liver function. Relative contraindications consist of active or systemic infection, as TIPS makes use of a foreign device that could act as a colonization site for bacteria, severe hepatic encephalopathy poorly controlled by medical therapy and portal vein thrombosis. 

At the time of writing, the authors are aware of only one commercially available device specifically designed for colonic insufflation (Fig. 5.5, Protocol colon insufflation system, E-Z-EM Inc, Westbury, NY, USA). This system electronically controls the flow rate of carbon dioxide increasing over time in a step wise fashion from 1 to 3 L/min to prevent spasm (1 L/min for the first 0.5 L, 2 L/min from 0.5 to 1.0 L, and then 3.0 L/min thereafter). The total volume of gas administered is displayed continuously and, if intracolonic pressure (measured at the rectal catheter tip) increases beyond the limit set by the user (up to a maximum of 25 mm Hg), the system automatically shuts down to prevent further insufflation and so reduces the risk of colonic perforation. In the latest version, insufflation automatically ceases when a total of 4 L of gas have been administered and then for every 2 L administered beyond this. To recommence insufflation, the operator needs to manually override this additional safety feature by pressing the start button. 

Patient compHance is stiU under debate, since colonoscopy is performed in most of the cases under sedation, without any pain suffered by the patient. However, the worst part of the exam is usually the pre-Hminary bowel cleansing (Gluecker et al. 2003). The advantage of CTC is the use of gentler preparation (now available) or unprepped examination (still under investigation). Furthermore, the pain related to colon distension by air may be minimized by the use of CO2 dehv-ered by an electronic pump with pressure and volume control. The use of CO2 is also associated with a faster resorption, making the patient more comfortable immediately after the examination (Burling et al. 2006). 

Marques et al. [49] used hydrothermal oxidation in HNO3 at elevated pressure (0.5 MPa) and temperature (120-200°C) to functionalize SWCNTs and to control both the type and amount of surface functional groups. Their results showed that the degree of surface functionalization is correlated with the HNO3 concentration by a first-order exponential function. Lebron-Colon et al. [53] used dye-assisted photo-oxidation to functionalize SWCNTs. Their stndy revealed that photo-oxidized SWCNT contain np to 40% more oxygen (11.3 at.%) bound to the tnbe snrface (chemisorption), as compared to H2S04-treated samples (6.7 at.%), primarily in the form of carboxylic, carboxylate, and ester groups. 

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