Amidated pectin/sodium carboxymethylcellulose microspheres as a new carrier for colonic drug targeting: Development and optimization by factorial design.

The colon is a promising site for drug targeting owing to its long transit time and mild proteolytic activity. The aim of this study was to prepare new low methoxy amidated pectin/NaCMC microspheres cross-linked by a mixture of Zn(2+) and Al(3+) ions and test their potential for colonic targeting of progesterone. A 2(4) factorial design was carried out to optimize the preparation conditions. High drug entrapment efficiency (82-99%) was obtained and it increased with increasing drug concentration but decreased with increasing polymer concentration. Drug release rate was directly proportional to the microsphere drug content and inversely related to Al(3+) ion concentration. Drug release was minimal during the first 3h but was significantly improved in the presence of 1% rat caecal contents, confirming the microsphere potential for colonic delivery. The microspheres achieved >2.3-fold enhancement of colonic progesterone permeability. These results confirm the viability of the produced microspheres as colon-targeted drug delivery vehicle.

Development and in vitro evaluation of novel floating chitosan microcapsules for oral use: comparison with non-floating chitosan microspheres.

Floating (F) microcapsules containing melatonin (MT) were prepared by the ionic interaction of chitosan and a negatively charged surfactant, sodium dioctyl sulfosuccinate (DOS). The DOS/chitosan complex formation was confirmed employing infrared spectroscopy, differential scanning calorimetry (DSC), solubility and X-ray diffraction analysis. The characteristics of the F microcapsules generated compared with the conventional non-floating (NF) microspheres manufactured from chitosan and sodium tripolyphosphate (TPP) were also investigated. The effect of various factors (crosslinking time, DOS and chitosan concentrations, as well as drug/polymer ratio) on microcapsule properties were evaluated. The use of DOS solution in coagulation of chitosan produced well-formed microcapsules with round hollow core and 31.2-59.74% incorporation efficiencies. Chitosan concentration and drug/polymer ratio had a remarkable effect on drug entrapment in DOS/chitosan microcapsules. The dissolution profiles of most of microcapsules showed near zero order kinetics in simulated gastric fluid (S.G.F: pH 1.2). Moreover, release of the drug from these microcapsules was greatly retarded with release lasting for several hours (t(50%) (S.G.F.): 1.75-6.7 h, depending on processing factors), compared with NF microspheres where drug release was almost instant. Most of the hollow microcapsules developed tended to float over simulated biofluids for more than 12 h. Swelling studies conducted on various drug-free formulations, clearly indicated that DOS/chitosan microcapsules showed less swelling and no dissolution in S.G.F. for more than 3 days, whereas, TPP/chitosan microspheres were markedly swollen and lost their integrity in S.G.F. within 5 h. Therefore, data obtained suggest that the F hollow microcapsules produced would be an interesting gastroretentive controlled-release delivery system for drugs.

Oral delayed-release system based on Zn-pectinate gel (ZPG) microparticles as an alternative carrier to calcium pectinate beads for colonic drug delivery.

A new oral timed-release system was developed for colon-targeted delivery of drugs. The system which consists of ketoprofen-loaded Zn-pectinate gel (ZPG) microparticles together with pectin/dextran mixtures in a tablet form, has been investigated, in vitro, using conditions chosen to simulate the pH and times likely to be encountered during transit to the colon. In order to find the suitable ZPG microparticles, the formulations were prepared by utilizing 2(3) factorial design and the effect of various formulation factors on the release and surface characteristics of the microparticles was studied. The results obtained implied that the release of ketoprofen from ZPG microparticles was greatly extended with the pectinate microparticles, which were prepared with 2.5 or 3% w/v pectin, 2.75% w/v Zn(CH3COO)2 and 2.5% w/v drug. Additionally, the analysis of variance results showed that the release of ketoprofen in simulated intestinal fluid (S.I.F., pH 7.4) was strongly affected by crosslinking agent concentration and initial drug amount, but not particularly affected by the amount of pectin added. The investigated drug concentration factor has significantly increased the drug entrapment efficiency (EE). The optimum colonic drug delivery ZPG/tablet system provided the expected delayed-release sigmoidal patterns with a lag-time of 4.125-4.85 h and t(50%) (the time for 50% of the drug to be released) at 7.45-8.70 h, depending on pectin/dextran ratio employed. The results also demonstrated that the untableted ZPG microparticles exhibited drug release profiles which were able to retard the release of ketoprofen in S.I.F. (pH 7.4) to be 5.28-37.82 times (depending on formulation parameters), lower than the conventional calcium pectinate beads. Therefore, this approach suggests that ZPG microparticles and their modified-release formulations are promising as useful controlled-release carriers for colon-targeted delivery of drugs.