In: Biology
A. Answer:
Benefits of colonic delivery systems are as follows:
1. Colon drug delivery systems (CDDS) offers considerable therapeutic benefits to patients in terms of both local and systemic treatment.
2. The colon is most suitable absorption site for peptides and protein drugs due to the following reasons:
Comparative proteolytic activity of colon mucosa is much less than that observed in the small intestine, thus CDDS protects peptide drugs from hydrolysis, and enzymatic degradation in duodenum and jejunum, and eventually releases the drug into ileum or colon which leads to greater systemic absorption and enhances bioavailability.
3. It reduces dosing frequency due to its controlled release of drug.
4. It reduces side effects due to reduction in dosing frequency.
5. It also increases patient compliance due to reduction in dosing frequency and side effects.
B. Answer:
Main ideal characteristcs of CDDS:
1. Drugs pooriy absorbed from upper GIT
2. Drugs for colon cancer.
3. Drugs that degrade in stomach and in small intestine.
4. Drugs undergo first pass effect.
5. Drugs for targetting.
6. polymers used in the design of CDDS should be non-toxic, biocompatable, inert etc.
Several mechanisms or approaches are used for site-specific drug delivery. Among the primary approaches for CDDS, These include:
1. Mechanisms or approaches used in triggering the drug release in the colon:
a. pH Sensitive Polymer Coated Drug Delivery to the Colon: polymers used like methyl methacrylate to enhances site specificity and drug release.
b. Delayed (Time Controlled Release System) Release Drug Delivery to Colon: Time controlled release system (TCRS) works based on gastric emptying time. Therefore, sustained or delayed release dosage forms are also very promising drug release systems.
c. Microbially Triggered Drug Delivery to Colon: This shows specific enzymatic activity of the microflora present in the colon like Reducing enzymes: Nitroreductase, Azoreductase, N- oxide reductase, sulfoxide reductase, Hydrogenase etc., Hydrolytic enzymes: Esterases, Amidases, Glycosidases, Glucuronidase, sulfatase etc.
2. Newly Developed Approaches for CDDS:
a. Pressure Controlled Drug-Delivery Systems: Pressure controlled colon-delivery capsules prepared using ethyl cellulose, which is insoluble in water. In such systems, drug release occurs following the disintegration of a water-insoluble polymer capsule because of pressure in the lumen of the colon.
b. Novel Colon Targeted Delivery System (CODESTM): CODESTM is a combined approach of pH dependent and microbially triggered CDDS. It has been developed by utilizing a unique mechanism involving lactulose, which acts as a trigger for site specific drug release in the colon.
c. Osmotic Controlled Drug Delivery (ORDS-CT): there are different types of Osmotic Controlled Drug Delivery systems. The OROS-CT (Alza Corporation) can be used to target the drug locally to the colon for the treatment of disease or to achieve systemic absorption.
Example: For treating ulcerative colitis, each push pull unit is designed with a 3-4 h post gastric delay to prevent drug delivery in the small intestine. Drug release begins when the unit reaches the colon. OROS-CT units can maintain a constant release rate for up to 24 hours in the colon or can deliver drug over a period as short as four hours.
C. Answer:
This CDDS makes more challenging in targetting the specific site due to the following reasons:
In this field to design a delivery system that would be robust enough to withstand the variability in the gastric pH as it moves from the stomach to the small intestine. By combining knowledge of polymers and their solubility at different pH environments, delivery systems have been designed to deliver the drug at the target site.
The site of drug release is decided by the transit time of a formulation in the GIT, which makes it challenging to develop a formulation in order to achieve a precise drug release in the colon. Ideally, formulations are designed such that the site of delivery (i.e. colon) is not affected by the individual differences in the gastric emptying time, pH of the stomach and small intestine or presence of anaerobic bacteria in the colon.
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