Characterization of drug release and diffusion mechanism through hydroxyethylmethacrylate/methacrylic acid pH-sensitive hydrogel

Hydroxyethylmethacrylate/methacrylic acid copolymer cross-linked with ethylenglycol dimethacrylate was prepared by a bulk free radical polymerization method. The permeability studies of this pH-sensitive hydrogel to drugs with different water solubilities showed a water-content dependent diffusion or pore mechanism for ephedrine HCl (water-soluble model drug), whereas, a partition or solute-diffusion mechanism for indomethacin (a water-insoluble drug) was seen. Data analysis of release tests, according to the swelling interface number and Peppas equation for ephedrine HCl in pH 7.4, showed a biexponential model kinetic, whereas in pH 1.2 a swelling-controlled mechanism was seen. Indomethacin was released by an anomalous or non-Fickian release kinetics.     

Drug permeation through artificial lipid membranes. 17. The mechanism of ion pair transport

The transport of ionized drugs across lipoid membranes can be increased considerable by lipophilic counter ions. This is caused by an increased lipophilicity of the ion pair which is formed between the ionized drugs and the lipophilic counterion. Caused by their very strong solubility in the membrane the lipophilic counterions accumulate and act like a carrier for the ionized drugs. Then the necessary compensation of the charges can take place by protons or other suitable ions of the used solution.     

Progestin permeation through polymer membranes IV: Mechanism of steroid permeation and functional group contributions to diffusion through hydrogel films.

Hydrogel films were prepared from hydroxyethyl methacrylate, both with (Film II) and withouth (Film I) 5.25 mole% of ethylene glycol dimethacrylate. Permeation, diffusion, and partition coefficients for progesterone, testosterone, nandrolone, norethindrone, 17 alpha-hydroxyprogesterone, estradiol, and hydrocortisone were determined. A solute permeation model was proposed based on the separation of a domain (B) composed of "bulk-like" water and a doman (A) composed of polymer, interfacial water, and bound water present in the films. The separate contributions from the "pore" and "solution-diffusion" mechanisms to the total permeability were calculated from the model. Steroid permeabilities through Films I and II were analyzed in accordance with this model. Permeation of Film II occurred via the solution-diffusion mechanism. Permeation of Film I occurred predominately by the pore mechanism with a small contribution (approximate 20%) from the solution-diffusion mechanism. The latter contribution was dependent on the solubility of the solute within the A domains of the hydrogel film. Functional group contributions to permeation of Film II were ascribed to either steric or hydrogen bonding effects.     

Progestin permeation through polymer membranes III: Polymerization solvent effect on progesterone permeation through hydrogel membranes.

Hydrogels prepared from poly(hydroxyethyl methacrylate) are biocompatible and highly permeable to low molecular weight solutes. Permeation rates can be varied by altering the cross-linker concentration or using copolymers; the latter are chosen to alter the hydrogel equilibrium hydration. These factors suggest that hydrogels are good candidates for controlled-release drug delivery devices. Hydrogels may be synthesized using various temperatures, initiators (nature and concentration), and solvents (nature and concentration). This study demonstrated that progesterone permeation through poly(hydroxyethyl methacrylate) films is independent of polymerization solvent (nature and concentration) for the solvents, water, ethanol, and tert-butyl alcohol. The importance of hydrogel equilibrium hydration in progesterone permeation is emphasized.     

A thermo- and pH-sensitive hydrogel composed of quaternized chitosan/glycerophosphate

The quaternized chitosan was synthesized by the reaction of chitosan and glycidyltrimethylammonium chloride (GTMAC) and named as N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC). A novel hydrogel system composed of HTCC/glycerophosphate (HTCC/GP) with thermo- and pH-sensitivity was synthesized and used as an intelligent drug carrier. The formulation was solution below or at room temperature, which allowed it injectable and to incorporate living cells, proteins, enzymes or other therapeutic drugs easily. Once the surrounding temperature was up to 37 degrees C, the system was transformed to a non-flowing hydrogel, and the formed hydrogel can release the trapped drug as a function of pH values. The swelling behavior of the system and the release profiles of doxorubicin hydrochloride (DX) as a model drug at different pH values were investigated. At acidic condition the hydrogel dissolved and released drug quickly, while it absorbed water and released drug slowly at neutral or basic conditions. Hydrogel composed of chitosan hydrochloride and glycerophosphate (CS/GP) was also prepared to compare with HTCC/GP hydrogel. The HTCC/GP hydrogel in this study was transparent which made it suitable for some specific uses such as ocular drug formulation.     

Self-assembly pH-sensitive chitosan/alginate coated polyelectrolyte complexes for oral delivery of insulin

Polyelectrolyte complexes (PEC) provide new opportunities for controlled release system of drugs, and have potentials to address challenges on the way to effective oral insulin delivery. Here, an innovative pH-sensitive PEC for insulin oral administration was developed, which was formed by self-assembly of two oppositely charged nanoparticles (chitosan-coated nanoparticles and alginate-coated nanoparticles) through electrostatic interaction via optimised double emulsion method. The encapsulation efficiency of insulin-loaded alginate-coated and chitosan-coated nanoparticles were 81.5?±?7.4% and 55.2?±?7.0%, respectively, and the particle size of these nanoparticles were in 200–300?nm range. The pH-dependent morphology of PEC was observed by transmission electron microscopy. The PEC exhibited insulin release profile triggered by pH in vitro and was non-cytotoxicity against Caco-2 cell. The insulin-loaded PEC could decrease blood glucose levels effectively and prolong insulin release after oral administration to diabetic rats. The results illustrated that the as-prepared PEC may be employed as a potential oral insulin delivery system.     

盐酸小檗碱透过羧甲基壳聚糖-海藻酸钠聚电解质水凝胶规律探究

目的 探究伤科黄水中黄连和黄柏的主要有效成分BBH在CMCS-SA体系中的传递与扩散规律。方法 CMCS和SA按照一定比例搅拌,加入GDL后形成聚电解质水凝胶。采用流变仪研究CMCS-SA的水凝胶的流变学性能,包括弹性模量G’和粘性模量G’’。设计针对CMCS-SA水凝胶的BBH扩散模型并通过UV观察BBH透过CMCS-SA聚电解质水凝胶的相关规律。 结果 测定CMCS与SA配比为3:1、 2:1、 1:1、 1:2、 1:3时的水凝胶弹性模量G’,当CMCS:SA=1:1时,G’最高,此时水凝胶交联强度最高。通过BBH传递模型测定其累积传递量,经Peppas方程拟合BBH在CMCS-SA水凝胶中的扩散为骨架溶蚀作用,表明随着CMCS的氨基减少或SA的羧基增加,BBH解离,传递效率增加。CMCS-SA水凝胶的弹性模量G’随着GDL含量增加而增加,是因为pH的降低导致CMCS和SA分子间的结合力逐渐增加,水凝胶交联度增强。固定CMCS与SA比例1:1, GDL含量0.15g/mL,CMCS-SA水凝胶成型性良好。此外BBH在不同浓度GDL的水凝胶中传递时,随着GDL含量增加,传递效率上升。BBH在不同厚度水凝胶中传递时,随着厚度减小, CMCS-SA水凝胶的传递效率增加。 结论 CMCS-SA水凝胶体系作为潜在的BBH等中药提取物的药物载体有望作为经皮给药的凝胶载体。     

Drug release from the enzyme-degradable and pH-sensitive hydrogel composed of glycidyl methacrylate dextran and poly(acrylic acid)

Hydrogels composed of glycidyl methacrylate dextran (GMD) and poly(acrylic acid, PAA) were prepared by UV irradiation method for colon-specific drug delivery. GMD was synthesized by coupling of glycidyl methacrylate to dextran in the presence of 4-(N,N-dimethylamino)pyridine. GMD was photo-polymerized by ammonium peroxydisulfate as initiating system in phosphate-buffered solution (0.1 M, pH 7.4). And then, acrylic acid monomer was added and subsequently heat-polymerized by 2,2'-azobisisobutyronitrile as an initiator. The hydrogels exhibited high swelling ratio (about 20) at 37 degrees C, and showed a pH-dependent swelling behavior. In addition, the swelling ratio of the hydrogel was remarkably enhanced to about 45 times in the presence of dextranase at pH 7.4. The swelling-deswelling behavior proceeded reversibly for the GMD/PAA hydrogels between pH 2 and pH 7.4. Release of 5-aminosalicylic acid from the GMD/PAA hydrogels was evaluated in simulated gastrointestinal pH fluids in the absence or presence of dextranase. We concluded that the hydrogels prepared could be used as a dual-sensitive drug carrier for sequential release in gastrointestinal tract.     

Drug permeation through membranes V: interaction of diazepam with common excipients.

The effects of common tablet excipients on the permeation of diazepam through polydimethylsiloxane membranes and on the turnover time of goldfish were studied. The permeability coefficient decreased and the turnover time increased in the presence of talc, polysorbate 80, and, possibly, fumed silicon dioxide, but these parameters were unaffected by lactose, microcrystalline cellulose, and starch.     

Drug transport through artificial lipoid membranes. 21. Ion pair transport with alkyl salicylic acids

Using hexylsalicylic acid it was demonstrated that alkylated derivatives of salicylic acid are able to increase partition and transport of ionized basic drugs across lipophilic membranes. The influence of different donor concentrations on the relation of transport was studied by means of pholedrine in combination with hexylsalicylic acid. In order to explain the mechanism of the ion-pair-transport experiments were carried out which show beside the mentioned increase of transport the occurrence of a countertransport of protons and lithium-ions, respectively. The lipophilic counterion hexylsalicylate acts inside of this mechanism as a carrier for the ionized drugs.