Design and evaluation of matrix base with sigmoidal release profile for colon-specific delivery using a combination of Eudragit and non-ionic cellulose ether polymers.

A pH- and time-controlled drug delivery system with sigmoidal release profile was developed using Eudragit (L100 or S100) in combination with hydroxy ethyl cellulose (HEC) or hydroxy propyl cellulose (HPC) for sigmoidal release of indomethacin in the potential treatment of colon cancer. The effect of varying proportions of polymer type on sigmoidal release was evaluated. The prepared tablets were also characterized for physical characteristics, in vitro drug release, release kinetics, and stability on storage. The gastrointestinal transit of formulations was also investigated in human subjects. Results from in vitro release studies indicated that due to the presence of pH-responsive polymers, a pH- and time-dependent release pattern was observed, which was characterized by negligible drug release in first 4-6 h followed by controlled release for 14-16 h in alkaline pH. In vivo studies indicated that HPC-based formulations had satisfactory matrix strength to withstand gastric and colonic transit, while HEC-based tablets disintegrated during transit through the small intestine. All the formulations were stable on storage. It was concluded that such a matrix design has good potential for drug delivery to colon with controlled release.

Design and in vitro evaluation of formulations with pH and transit time controlled sigmoidal release profile for colon-specific delivery.

The primary objective of the study was to develop a pH and transit time controlled sigmoidal release polymeric matrix for colon-specific delivery of indomethacin. Tablet matrices were prepared using a combination of hydrophilic polymers (polycarbophil or carbopol) having pH sensitive swelling properties with hydrophobic polymer ethyl cellulose. The prepared matrices were characterized for physical properties and in vitro release kinetics. The presence of ethyl cellulose in a hydrophilic polymer matrix resulted in a sigmoidal in vitro drug release pattern with negligible to very low drug release in the initial phase (0-6 h) followed by controlled release for 14-16 h. The retardation in initial release can be attributed to the presence of ethyl cellulose that reduced swelling of hydrophilic polymer(s) while in the later portion, polymer relaxation at alkaline pH due to the ionization of acrylic acid units on carbopol and polycarbophil resulted in enhanced drug release. Thus, a sigmoidal release pattern was obtained that could be ideal for colonic delivery of indomethacin in the potential treatment of colon cancer.

Design and evaluation of matrices of Eudragit with polycarbophil and carbopol for colon-specific delivery.

The purpose of the present study was to investigate the effect of incorporating pH-responsive polymers Eudragit (L100 or S100) in matrix bases composed of hydrophilic polymers polycarbophil and carbopol to design oral controlled release formulations with sigmoidal release profile for colon-specific delivery. Matrix tablets were prepared by wet granulation technique using indomethacin as model drug and were characterized for physical parameters, in vitro drug release, release kinetics, and stability on storage. The gastrointestinal (GI) transit of selected formulations was also investigated in human subjects using gamma scintigraphy. In vitro release studies indicated that the presence of pH-sensitive polymers in hydrophilic polymer base retarded the initial release significantly (10-15% release in 6 h) followed with controlled release for the next 8-10 h in simulated GI fluid pH (without enzymes). The presence of Eudragit in hydrophilic matrix base retarded the swelling of the matrix base in acidic to weakly acidic pH, but in alkaline pH, enhancement in drug release rate was observed due to the dissolution of Eudragit from the base resulting in a porous matrix structure, resulting in around 80-90% release in 14 h of study. In vivo gamma scintigraphy studies in healthy human subjects proved that the formulations had acceptable matrix strength to withstand gastric and colonic transit. The mean colonic residence time of selected designed formulations varied between 15 and 19 h. Such a matrix design could have potential application as colon-specific drug delivery systems with pH- and time-dependent drug release profile.

Multiparticulate formulation approach to colon specific drug delivery: current perspectives.

Colon specific drug delivery has gained increased importance not just for the delivery of drugs for the treatment of local diseases associated with the colon but also as potential site for the systemic delivery of therapeutic peptide and proteins. To achieve successful colon targeted drug delivery, a drug needs to be protected from degradation, release and/or absorption in the upper portion of the GI tract and then ensure abrupt or controlled release in the proximal colon. Drug modifications through covalent linkages with carrier or prodrug approach and formulation based approaches can be used for colonic delivery. Report suggests that drug carrier systems larger than 200 mm possess very low gastric transit time due to physiological condition of the bowel in colitis. And for this reason and considering the selective uptake of micron or sub-micron particles by cancerous and inflamed cells/ tissues a multiparticulate approach based on pellets, granules, microsphere or nanoparticle type formulation is expected to have better pharmacological effect in the colon. The review is aimed at understanding recent advancements made in multiparticulate formulation approach for colon specific delivery of medicaments.