Alaa Eldeen B. Yassin

In Vitro Characterization of Carbamazepine-Loaded Precifac Lipospheres

Lipospheres of carbamazepine were prepared by melt dispersion technique using Precifac® ATO 5 in the various drug-lipid ratios. The resulting free-flowing lipospheres were evaluated with respect to surface morphology, particle size distribution, encapsulation efficiency, and in vitro release behavior. The effect of druglipid ratio, the surfactant added, emulsion stabilizer, and stirring speed also were identified as the key variables affecting the formation of discrete spherical lipospheres and drug release rate. The preparation conditions were optimized by using 0.4% w/v span 20 (Hydrophilic-Lipophilic Balance, HLB=8.6) as a surfactant and 1% w/v gelatin solution as a stabilizer in presence of a high level of water.We found that the ratio of drug to lipid affects the size of the spheres. The incorporation efficiency was found to be high at all loadings. Increasing the lipid:drug ratio produced more spherical, smooth, and round lipospheres. All the prepared lipospheres exhibited slow release profiles dictating the Higuchi mode of release. We saw that the higher the sphere size and the ratio of Precifac®, the slower is in vitro drug release.

New targeted-colon delivery system: in vitro and in vivo evaluation using X-ray imaging

The aim of this study was to formulate a new orally-administered colon delivery system of 5-flurouracil (5-FU) for the treatment of colon cancer. The system was designed to target 5-FU directly to the colon with high potential of much more effective and less toxic colon cancer treatment. The system was prepared by compression coating technique using granulated chitosan. The method was optimized by studying the effect of granulation and thickness of the coat with respect to the in vitro performance in a medium mimicking mouth-to-colon environment. The in vivo selectivity of the system was assessed by X-ray imaging technique using beagle dogs. Results showed that granulation of chitosan were effective in protecting against the known acid solubility of the polymer. Formula (F7) with coat weight of  50 mg/tablet exhibited the best protection profile with <10% of the drug released after 6 h. The resistance of the system to the simulated gastro-intestinal media was reduced as the chitosan coat weight decreases. The performance of the system in a rat caecal contents containing-medium showed that the susceptibility of this system for the enzymatic degradation by colonic enzymes. The X-ray imaging gave rise to the in vivo selectivity of this system for colon targeting by showing the resistivity of the system to the stomach and small intestine environment and the selective disintegration of the system inside the large bowel.

A new pressure-controlled colon delivery capsule for chronotherapeutic treatment of nocturnal asthma

The purpose of this study was to prepare a pressure-controlled colon delivery capsule (PCDC) containing theophylline (TPH) dispersion in a lipid matrix as a chronotherapeutic drug delivery system for the treatment of nocturnal asthma. The system was made by film coating using Eudragit S100- based formula over the sealed-hard gelatin capsules containing the drug-lipid dispersion. The lipid formula was composed mainly of Gelucire 33/01 (G33) with different ratios of surfactants (1–10%). The efficiency of the prepared system was evaluated in vitro for its ability to withstand both the gastric and intestinal medium. In addition, the drug plasma concentrations were monitored after single administration to Beagle dogs and compared to that obtained after administration of a reference marketed, generic, sustained-release TPH tablets, Avolen® SR. It was found that the optimum lipid formula was GL2 containing 90% G33 and 10% Labrasol. The film-coated capsules showed complete resistance to both the acidic environment (pH 1.2) for 2 hours and phosphate buffer pH 6.8 for 3 hours at 37°C. In vivo evaluation of the TPH-based PCDCs showed longer lag time compared TO the marketed formula followed by sudden increase in TPH blood levels, which recommends the high potential of this system as a chronotherapeutic drug delivery for nocturnal asthma. The prepared PCDCs exhibited a significantly higher Cmax and Tmax and a nonsignificantly different AUC compared with Avolen® SR. Higher TPH blood levels from 1 to 8 hours postadministration was detected in the case of the prepared PCDCs.

Theophylline colon specific tablets for chronotherapeutic treatment of nocturnal asthma

The ultimate goal is to design a new chronotherapeutic system for theophylline (TPH) with high potential benefits in treating nocturnal asthma. TPH core tablets were prepared by wet granulation using a developed formula. Compression coating over core tablets containing 200 mg TPH was done using granulated chitosan with 10% PVP K30. Different formulae F1, F2 and F3 were prepared using coat weights 260, 300 and 360 mg, respectively. The in vitro release characteristics in both variant pH media mimicking the gastrointestinal media and in media containing rat cecal content were monitored. The in vivo performance of the optimum formula was compared with Avolen® SR in Beagle dogs. F3 with high coat thickness exhibited a minimal release after 5-h release study. Both F2 and F3 showed more than 50% drug release after 4 h in the rat cecal medium. This reflects the colon selectivity of the system. The Cmax values were found to be 5.49 ± 0.46 and 5.12 ± 0.85 μg/mL for F3 and Avolen® SR, respectively, F3 showed higher mean plasma concentration than Avolen® SR from the beginning and continued till 7 h post administration indicating high potential as chronotherapeutic treatment of nocturnal asthma.

Novel erythropoietin-loaded nanoparticles with prolonged in vivo response.

The aim of this study was to incorporate human recombinant erythropoietin (EPO) in biodegradable polymeric nanoparticles targeting a prolonged-release effect. EPO-loaded poly(DL-lactide-co-glycolide) nanoparticles were prepared using double emulsion method (w/o/w) with least process-related stress on the encapsulated drug. The nanoparticles have been fully characterized including in vitro release profile. The biological activity was assessed in vivo using BALB-c mice. The produced particles appeared spherical in shape with smooth regular surfaces and had an average particle size of 225.9 ± 3.8 nm. The entrapment efficiency was 33.3%. The in vitro release profile exhibited a biphasic mode with a burst of 50% cumulative drug release, followed by a slow rate of release over 24 h, reaching a maximum of 82%. The bioassay results showed that EPO-loaded nanoparticles were able to maintain the physiological activity of EPO for 14 days after single subcutaneous injection compared with pure and marketed EPO formulae (EPREX®).