A new controlled-release liquid delivery system based on diclofenac potassium and low molecular weight chitosan complex solubilized in polysorbates.

A complex of low molecular weight chitosan (LMWC) with oleic acid and diclofenac potassium (DP) was prepared and dispersed in high concentrations of polysorbate 20, 60 and 80 in water to form a solution which releases its components slowly. The formed complex was characterized using different analytical methods. The size of the resulted nanoparticles and the effect of tweens on size were followed using dynamic light scattering (DLS). The release of DP from this delivery system was monitored by altering the molecular weight of chitosan and the type and concentration of the polysorbates used. The most suitable preparation consisted of DP, LMWC 13 kDa, and oleic acid. This was dispersed in 5% Tween 80 and the release was followed by the adaptation of USP II apparatus using a cellophane bag. This preparation offers a release of up to 24 h.

Controlled release of tramadol hydrochloride from matrices prepared using glyceryl behenate.

An inert matrix to control the release of tramadol HCl was prepared using glyceryl behenate as a matrix-forming agent. The matrices were prepared by either direct compression of a physical mixture of the drug and the matrix-forming agent or by compression of granules prepared by hot fusion of the drug and the matrix-forming agent. The hot fusion method was found to be more effective than compression of physical mixtures in retarding the release of the drug from the matrix. Drug release was adjusted by using release enhancers, such as microcrystalline cellulose and lactose, and the results showed that higher release rates were obtained using lactose. However, the release of the drug was independent of the compression force and the pH of the dissolution medium. This study showed that glyceryl behenate is an appropriate waxy material that can be used as a matrix-forming agent to control the release of a water-soluble drug such as tramadol HCl.

Characterization of protein release through glucose-sensitive hydrogel membranes.

Glucose-sensitive phase-reversible hydrogels have been prepared based on the specific interaction between polymer-bound glucose and concanavalin A (Con-A). The main goal of this study was to characterize the release of model proteins (insulin and lysozyme) through the hydrogel membrane as the free glucose concentration in the environment was changed. The diffusion of the model proteins through the hydrogel membrane was examined using a diffusion cell. Porous poly(hydroxyethyl methacrylate) (PHEMA) membranes were used to sandwich the mixture of glucose-containing polymers and Con-A in between the donor and receptor chambers. The porous PHEMA membranes allowed diffusion of glucose, insulin and lysozyme, while preventing loss of glucose-containing polymers and Con-A in the sol state. The release rate of model proteins through the glucose-sensitive hydrogel membrane was dependent on the concentration of free glucose. The release rate of the proteins did not remain constant, however, due to the change in free glucose concentration resulting from diffusion of glucose from the receptor chamber to the donor chamber. This study demonstrated the possibility that the glucose-sensitive phase-reversible hydrogels can be used to regulate the insulin release as a function of the free glucose concentration in the environment.

Characterization of glucose dependent gel-sol phase transition of the polymeric glucose-concanavalin A hydrogel system.

PURPOSE: The main goal of this study was to synthesize and characterize hydrogels which undergo reversible gel-sol phase transformation in response to changes in glucose concentration in the surrounding environment. METHODS: The glucose-sensitive hydrogels were made by mixing the appropriate concentrations of acrylamide-allyl glucose copolymer and concanavalin A (Con A). To examine their phase reversibility, hydrogels in dialysis membranes were cycled between glucose-free and glucose-containing buffers. The binding affinity of allyl glucose (AG) to Con A was examined by using an equilibrium dialysis technique. RESULTS: The synthesized hydrogels underwent phase transition to sol in the presence of free glucose in the environment. The concentration of external free glucose (Cf) had to be at least 4 times that of polymer-bound glucose (Cp) to induce phase transition from gel to sol. The binding affinity study showed that binding of AG to Con A was four times stronger than that of free glucose. When Cp in the gel was 0.42 mg/ml or higher, Cf had to be much higher than 4 times Cp to induce phase transition. CONCLUSIONS: The synthesized hydrogels underwent phase transition in the presence of free glucose in the environment, but the phase transition was not linearly dependent on the concentration of free glucose. This non-linear dependence was explained by the increased binding affinity of AG over native glucose to Con A, and the cooperative interactions between polymer-bound glucose and Con A.