Application of pressure-controlled colon delivery capsule to oral administration of glycyrrhizin in dogs

Abstract

A colon delivery system has been used to improve the bioavailability of glycyrrhizin, a glycoside of glycyrrhetic acid. The bioavailability of glycyrrhizin is low when administered in conventional oral galenic dosage forms because glycyrrhizin is enzymatically hydrolysed both in the stomach and in the intestine. It was reasoned that if large amounts of glycyrrhizin were directly delivered to the colon, enzymatic activity should be reduced due to saturation so that intact glycyrrhizin could be absorbed into the systemic circulation. Based on this assumption, pressure-controlled colon delivery capsules (PCDCs) were used as a colon delivery system. Eight types of glycyrrhizin solution were prepared and were introduced into PCDCs. After oral administration of the test PCDCs to beagle dogs, blood samples were obtained over 24 h and plasma glycyrrhizin concentrations were measured by an HPLC method. With PCDCs containing aqueous glycyrrhizin and propylene glycol solutions, plasma glycyrrhizin levels were extremely low and the bioavailabilities of glycyrrhizin were 0.6% and 0.4%, respectively. When Labrasol was added to both types of glycyrrhizin solution, the bioavailability was improved to 4.6% for aqueous solution and 3.8% for propylene glycol solution. When a surfactant, Polysorbate 80, was added in combination with Labrasol, synergistic effects were not obtained. Furthermore, dose-dependent effects of Polysorbate 80 were not obtained. Labrasol, which is a component of self-emulsifying drug delivery systems (SEDDS), has been shown to strongly improve the bioavailability of glycyrrhizin from the colon.

Pectin Matrix as Oral Drug Delivery Vehicle for Colon Cancer Treatment

“…It is practically difficult to utilize transit time as a measure to target drug delivery of these systems at colon. The suitability of pressure-dependent systems is a function of the reproducibility in pressure and duration of peristaltic waves as well as of disease condition (34). The high-pressure phases in colon are known to be infrequent and follow circadian rhythm with maximum frequency after waking, meals, and with defecation.…”

Can colorectal delivery technology provide a platform for enteral oligonucleotide-based therapeutics?

“…Our systemic delivery technique for nucleic acids via the large intestine not only has the potential to be developed into a drug for use as an enema or suppository, but could also be developed into an oral drug, taking advantage of a colonic drug delivery system (18)(19)(20). Thus, this colorectal delivery technique may provide a new foundation for the development of oligonucleotide-based oral therapeutics.…”

Liberação específica de fármacos no cólon por via oral. II - Tipos de sistemas utilizados

“…As formulações designadas de PCDC ® ("Pressure control colon delivery capsule"), consistem em cápsulas cuja liberação específica no cólon é controlada pela pressão. As cápsulas apresentam a forma de supositórios de polietilenoglicóis (PEG), revestidas por etilcelulose (Takaya et al, 1995;Hu et al, 2000a;Shibata, et al, 2001). Quando administradas oralmente, vão comportar-se como um "balão" de etilcelulose, uma vez que a sua base se liquefaz à temperatura corporal.…”