Pharmaceutical and pharmacokinetic evaluation of novel rectal mucoadhesive hydrogels containing tolmetin sodium

Abstract

The objective of the present study was to develop rectal mucoadhesive hydrogels loaded with Tolmetin Sodium, a nonsteroidal anti-inflammatory drug, for prolonged duration of action and increased bioavailability. Fourteen formulae were prepared with different types and concentrations of polymers as hydroxypropylmethyl cellulose, hydroxylethyl cellulose, carboxymethyl cellulose and sodium alginate. Each formulation contain Tolmetin Sodium equivalent to 5% w/w active drug. The effect of the employed gel bases on pH, gel strength, mucoadhesion, viscosity and the in vitro release profile of drug was examined. In addition, hydrogel formulations were subjected to rheological and stability studies. The physicochemical characterization revealed that all hydrogels had a suitable pH (6.64-7.75) and gel strength (15.5-65.29 s) for rectal application. The in-vitro drug release from the formulations showed a controlled drug release pattern, reaching 72-92.6% after 8 h. The kinetic analysis of the release data revealed that the drug release from all tested hydrogel bases obeyed the diffusion mechanism. The degradation of Tolmetin Sodium from its rectal hydrogel formulations was found to be a zero-order reaction. All formulations except sodium alginate hydrogel were quite stable. Considering the in-vitro release, rheological properties and shelf life, (CMC; 2%w/w) hydrogel formula was the best among the studied formulations. Therefore, further histopathological and bioavailability studies were carried out to detect different pharmacokinetic parameters of the established formulations compared with commercially available capsules. Formula containing 2% CMC showed relative bioavailability 357.93%. Finally, good correlation was observed between in-vitro and in-vivo profile.

pH‐responsive squeezing polysaccharidic nanogels for efficient docetaxel delivery

“…A variety of nano‐sized drug delivery systems (DDS) have been designed to increase the bioavailability of antitumor drugs, improve drug delivery efficiency to specific sites, and enhance antitumor efficacy of drugs . Resesarch interests have been focused on the development of pH‐responsive drug carriers, taking advantage of the weak acidity characteristic (ie, pH 6.5‐7.0) outside the tumor cells and the endosomal/lysosomal acidic pH characteristic inside the tumor cells .…”

“…In this respect, polysaccharidic drug carriers are most suitable for this purpose, and functional groups rich in biodegradable/biocompatible polysaccharides can be also utilized for next generation DDS applications . Agreeing with this situation, if novel types of chemotherapeutic drug carriers are developed through a chemical modification strategy of polysaccharides, it is likely to provide a transition period for chemotherapy …”

Hydrogels Based Drug Delivery Synthesis, Characterization and Administration

“…Following these standards, different injectable hydrogels protocols were developed and optimized, which because the body very well tolerated them, are ideal candidates for performing in vivo testing on rodents [176]. Given the fact that these delivery systems are suitable for clinical use, the most accessible routes of administration are subcutaneous [177], oral [178], rectal [179], topical and transdermal [180], orthotopic [181], intraperitoneal [182] and ocular [183]. Figure 3 represents all these administration routes.…”

“…Based on an earlier study that showed excellent biocompatibility on the digestive tract [195], rectally administrated catechol-chitosan- based hydrogels with mucoadhesive properties have been tested in murine models and show no toxic effects after 10 days [196]. Regarding this issue, Afaf A. et al, developed a hydrogel-based product and made a correlation between in vitro and in vivo profile with promising results [179].…”

Quality by Design Approach for Development and Optimization of Nitrendipine Loaded Niosomal Gel for Accentuated Transdermal Delivery

“…The drug content was quantified by dispersing 1 g gel in 25 ml of methanol and centrifuged at 15000 rpm at 4 °C for 30 min. The analysis was done in triplicate and the percentage drug content was calculated [37].…”