Sustained Release Of Water-soluble Drugs Research Articles

Evaluating Release Kinetics from Alginate Beads Coated with Polyelectrolyte Layers for Sustained Drug Delivery.

Current approaches in stem cell-based bone tissue engineering require a release of bioactive compounds over up to 2 weeks. This study presents a polyelectrolyte-layered system featuring sustained release of water-soluble drugs with decreased burst release. The bioactive compounds adenosine 5'-triphosphate (ATP), suramin, and A740003 (a less water-soluble purinergic receptor ligand) were incorporated into alginate hydrogel beads subsequently layered with different polyelectrolytes (chitosan, poly(allyl amine), alginate, or lignosulfonate). Drug release into aqueous medium was monitored over 14 days and evaluated using Korsmeyer-Peppas, Peppas-Sahlin, Weibull models, and a Langmuir-like "Two-Stage" model. Release kinetics strongly depended on both the drug and the polyelectrolyte system. For ATP, five alternating layers of poly(allyl amine) and alginate proved to be most effective in sustaining the release. Release of suramin could be prolonged best with lignosulfonate as polyanion. A740003 showed prolonged release even without layering. Applying polyelectrolyte layers significantly slowed down the burst release. Release curves could be best described with the Langmuir-like model.

Microparticles for sustained release of water-soluble drug based on a containment, dry coating technology.

Controlled release microparticles in a sub-gram-scale batch were fabricated using a ball mill, dry coating technique, to coat the water-soluble core material. This process also guaranteed the maintenance of the containment's integrity during the dry coating process. Quinine (average diameter, ca. 10 μm) and carnauba wax were used as the core and coating material, respectively. We evaluated the influence of process time, milling speed, and quinine-to-carnauba wax ratio on the particle size of the coated particles and their in vitro drug release profiles. Scanning electron microscopic observations suggested that the small wax particles attached to the core (quinine) particles resulted in a smooth film during the dry coating process. The size distribution of the coated particles agreed with the theoretically estimated size distribution. The in vitro release test demonstrated that the coated particles released quinine over 2 h in a biphasic mode. These results suggest that dry coating of microparticles less than 50 µm (D99) is feasible on a several-grams-batch scale. This new ball mill-coating technique also enables a guaranteed containment, a prerequisite for the manufacturing of highly bioactive or biohazard substances.

Electrospinning of calcium phosphate-poly (d,l-lactic acid) nanofibers for sustained release of water-soluble drug and fast mineralization.

Calcium phosphate-based biomaterials have been well studied in biomedical fields due to their outstanding chemical and biological properties which are similar to the inorganic constituents in bone tissue. In this study, amorphous calcium phosphate (ACP) nanoparticles were prepared by a precipitation method, and used for preparation of ACP-poly(d,l-lactic acid) (ACP-PLA) nanofibers and water-soluble drug-containing ACP-PLA nanofibers by electrospinning. Promoting the encapsulation efficiency of water-soluble drugs in electrospun hydrophobic polymer nanofibers is a common problem due to the incompatibility between the water-soluble drug molecules and hydrophobic polymers solution. Herein, we used a native biomolecule of lecithin as a biocompatible surfactant to overcome this problem, and successfully prepared water-soluble drug-containing ACP-PLA nanofibers. The lecithin and ACP nanoparticles played important roles in stabilizing water-soluble drug in the electrospinning composite solution. The electrospun drug-containing ACP-PLA nanofibers exhibited fast mineralization in simulated body fluid. The ACP nanoparticles played the key role of seeds in the process of mineralization. Furthermore, the drug-containing ACP-PLA nanofibers exhibited sustained drug release which simultaneously occurred with the in situ mineralization in simulated body fluid. The osteoblast-like (MG63) cells with spreading filopodia were well observed on the as-prepared nanofibrous mats after culturing for 24 hours, indicating a high cytocompatibility. Due to the high biocompatibility, sustained drug release, and fast mineralization, the as-prepared composite nanofibers may have potential applications in water-soluble drug loading and release for tissue engineering.

Konjac glucomannan/xanthan gum enzyme sensitive binary mixtures for colonic drug delivery

The polysaccharide konjac glucomannan (KGM) is degraded in the colon but not the small intestine, which makes it potentially useful as an excipient for colonic drug delivery. With xanthan gum (XG) KGM forms thermoreversible gels with hitherto unexplored biodegradation properties. In this work, rheological measurements of KGM and KGM/XG systems incubated with and without Aspergillus niger β-mannanase (used to mimic colonic enzymes) showed that KGM was degraded by the enzyme even when interacting with XG. Tablets with KGM/XG/sucrose matrices that varied in accordance with a simplex design and bore diltiazem as a typical highly soluble drug load were prepared by wet granulation, and in most cases were found to possess satisfactory mechanical strength and exhibit slow, nearly zero-order drug release. Drug release from these tablets remained zero-order, but was accelerated (presumably due to degradation of KGM), in the presence of A. niger β-mannanase at concentrations equivalent to human colonic conditions. However, marked differences between Japanese and American varieties of KGM as regards degree of acetylation and particle size led to significant differences in swelling rate and drug release between formulations prepared with one and the other KGM: whereas a formulation with Japanese KGM released its entire drug load within 24 h in the presence of β-mannanase, only 60% release was achieved under the same conditions by the corresponding formulation with American KGM, suggesting that with this KGM it will be necessary to optimize technological variables such as compression pressure in order to achieve suitable porosity, swelling rate, and drug release. To sum up, the results of this study suggest that sustained release of water-soluble drugs in the colon from orally administered tablets may be achieved using simple, inexpensive formulations based on combinations of KGM and XG that take the variability of KGM characteristics into account.

Polymer‐surfactant nanoparticles for sustained release of water‐soluble drugs

Poor drug encapsulation efficiency and rapid release of the encapsulated drug limit the use of nanoparticles in biomedical applications involving water-soluble drugs. We have developed a novel polymer-surfactant nanoparticle formulation, using the anionic surfactant Aerosol OT (AOT) and polysaccharide polymer alginate, for sustained release of water-soluble drugs. Particle size of nanoparticles, as determined by atomic force microscopy and transmission electron microscopy, was in the range of 40-70 nm. Weakly basic molecules like methylene blue, doxorubicin, rhodamine, verapamil, and clonidine could be encapsulated efficiently in AOT-alginate nanoparticles. In vitro release studies with basic drug molecules indicate that nanoparticles released 60-70% of the encapsulated drug over 4 weeks, with near zero-order release during the first 15 days. Studies with anionic drug molecules demonstrate poorer drug encapsulation efficiency and more rapid drug release than those observed with basic drugs. Further studies investigating the effect of sodium concentration in the release medium and the charge of the drug suggest that calcium-sodium exchange between nanoparticle matrix and release medium and electrostatic interaction between drug and nanoparticle matrix are important determinants of drug release. In conclusion, we have formulated a novel surfactant-polymer drug delivery carrier demonstrating sustained release of water-soluble drugs.

Sustained release of water-soluble drug from directly compressed alginate tablets.

The release of acetyl salicylic acid from directly compressed alginate tablets was investigated. The effect of the amount and type of alginate on the drug release rate was evaluated in different formulations. Four different grades of alginate were used. The in vitro release studies were carried out using the apparatus II (paddle) equipment as described in the USP 23/NF dissolution monograph. Dissolution medium was 0.1 M HCl for 2 h followed by phosphate buffer pH 6.8; both at 37 degrees C. Sustained drug release up to 16 h was achieved using sodium alginate in combination with dibasic calcium phosphate.

Modelling of sustained release of water-soluble drugs from porous, hydrophobic polymers

The release behaviour of water-soluble drugs from hydrophobic, porous polymeric matrices is complicated by the dissolution of the drug in the water-filled pores under quiescent conditions. Mathematical models are presented for drug release above and below the solubility limit of the drug in the dissolution medium, for constant void fraction (porosity). Experimental studies of KCI release from porous ethyl cellulose tablets in water at 37°C are explained in terms of dissolution-controlled and diffusion-controlled steps of the release mechanism.