Oral drug administration is the most commonly used route due to many advantages that can be driven from it which are higher patient compliance, lower pain. Ease of administration and decrease levels of infection.
Delivering drugs to their site of action leads to lower side effects and to increase pharmacological action. One of the interesting areas to target drugs through oral route is the colon(2-3). colon related diseases such as Crohn’s disease, ulcerative colitis, inflammatory bowel disease, colorectal cancer, and many others have taken a huge interest in their treatment that can be achieved by colon targeting.
Colon-targeted drug delivery systems provide potential advantages like delivery of high local drug concentration at the impaired part of the colon to produce optimum therapeutic action and reduction in systemic adverse effects associated with the premature release and subsequent absorption of drugs from the upper gastrointestinal tract this differentiate it from the classical oral dosage forms.
covalent linkage of a drug with a carrier, time-dependent release systems, coating with pH-sensitive polymers and enzymatically controlled delivery systems which is also called a (microbially triggered system) are Various systems that have been developed for colon-specific drug delivery:
The drawbacks of these systems are: pH-sensitive systems exhibit unpredictable site specificity of drug release because similar pH values of small intestinal and colonic fluids(8), A time-dependent system has difficulty for accurate prediction of site for drug release because of wide variation in gastric retention time(9) also Microbially triggered systems are affected by factors that may change the composition of the human gut ecosystem(10-11) and a larger amount of coat is required to prevent premature drug release due to higher hydrophilicity of the polysaccharides(12).
The union of two or more approaches has shown superior results regarding colon-specific drug release, namely minimal drug release in the stomach and small intestine and huge amount of drug released in the colon(13).
Film coating or compression coating processes are the processes that have been used for colon drug delivery system. Compression coating is a solvent-free process which is safe and inexpensive and it has higher stability when compared to film coating, but it suffers from disadvantages like the requirement of highly skilled persons and more care during compression to avoid compression-related problems(14).
Compression -coated tablets as colonic release systems are usually obtained by coating the drug cores by compression-coating(15-16). The polymers in the coating layers are usually soluble or insoluble matrix-forming polymers, capable of controlling drug release by matrix dissolution or erosion(17). polysaccharides which control drug release through their enzymatic degradation by the colonic microflora(4) or enteric polymers, which are insoluble in acidic media, but dissolve in slightly acid to neutral pH environments(18).
Hydrophilic polymers are highly used in formulating oral controlled-release tablets.
Hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) are the most often used polymers In the development and production of hydrophilic matrix tablets, When a hydrophilic matrix dosage form is exposed to the gastrointestinal fluid, the polymer on the surface of the dosage form hydrates and swells, forming a protective gel layer from which the drug is gradually and continuously released over time(20-21). Considering the solubility interplay between the drug and polymer, the release is diffusion-controlled if the solubility of the incorporated drug is greater than the solubility of the polymeric matrix. In contrast, the release is more erosion-controlled if the solubility of the polymeric matrix is greater than the solubility of the incorporated drug(
pectin, chondroitin sulfate, amylase, guar gum, xanthan gum and chitosan are examples of polysaccharides that are being examined as carriers for colon-specific drug delivery(29).
There are large amounts of polysaccharides that are present in the human colon as the colon is inhabited by a large number and variety of bacteria which secrete many enzymes e.g amylase, pectinase, xylanase, etc (27). Major approaches utilizing polysaccharides for colon-specific delivery are a fermentable coating of the drug core, embedding of the drug in the biodegradable matrix, formulation of drug saccharine conjugate(28).
Ketoprofen belongs to nonsteroidal anti-inflammatory drug it is used as an analgesic and an anti-inflammatory drug for the treatment of pain and rheumatic diseases. Ketoprofen is considered a good candidate for colon delivery due to the well known gastric side effect. Thus, there are several research works that studied the strategies of oral administration and colon-specific release of ketoprofen