Research Progress of Preparation Technology of Ion-Exchange Resin Complexes.

As insoluble polymer materials, ion-exchange resins (IERs) can exchange their own ions with desirable charged ions in the solution. According to the affinity of active moieties for soluble counterions, IERs could be categorized into the following four types: strongly acidic cation, weakly acidic cation, strongly basic anion, and weakly basic anion exchange resins. Due to their relative safety and high drug-loading capacity, IERs have garnered extensive attention in the pharmaceutical field since the 1950s. As numerous investigations combine drugs with IERs, this article summarizes the technologies employed in these studies from four aspects: IER screening principles, combining technologies, characterization methods, and in vitro and in vivo release of drug-resinate complexes. In addition, the advantages and disadvantages of various technologies and their scope are expounded. The article provides new insights on the preparation of ion-exchange resin complexes.

Assessment of taste masking of captopril by ion-exchange resins using electronic gustatory system.

The objective of the study was to mask the unpleasant taste of captopril (CPT). Taste masking was achieved by complexation of CPT with a basic ion exchange resin, Dowex® 66, using the batch method. Dowex® 66 was used for the adsorption of CPT, and physical and chemical parameters of the CPT resinates complex were evaluated. A central composite design was used to generate the experiments for the manufacture of resinates using different process and formulation variables. In vitro dissolution studies were performed for 2 h in 0.01N HCl (pH 1.6) using USP Apparatus I. The compatibility of CPT and the resin was evaluated by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). The resinates were evaluated for micromeritic properties and further characterised using FTIR, DSC, and PXRD. Response surface methodology was used to determine the significance of input variables on the CPT content and release. The CPT resin ratio was found to have a significant impact on content of the resinates and on CPT release. The formulations were also studied for taste masking ability by means of an electronic gustatory system - electronic tongue.

Effects of aspirin and clopidogrel on neural stem cells.

Cerebral infarction causes severe morbidity and mortality. Most patients with cerebral infarction should take antiplatelet drugs daily, so the effects of those drugs on the regeneration of the brain need to be investigated. Aspirin and clopidogrel are the most widely used antiplatelet drugs for the prevention of ischemic stroke. We investigated the effects of aspirin and clopidogrel on neural stem cells (NSCs). NSCs were dissociated from fetal rat cortex and cultured with basic fibroblast growth factor and N2 medium. To measure the effects of aspirin and clopidogrel on NSCs, NSCs were treated with several concentrations of aspirin, clopidogrel bisulfate, and clopidogrel resinate for 24 h. After the treatment, we measured cell viability by cell counting kit-8, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, trypan blue staining, flow cytometry, and lactate dehydrogenase assay. To evaluate their effects on NSC proliferation, we performed BrdU cell proliferation assay and colony-forming unit assay. We compared the intracellular protein level in the NSCs treated with aspirin and two types of clopidogrel, by proteomics analysis. Various viability tests showed that clopidogrel resinate and clopidogrel bisulfate did not affect the viability and proliferation of NSCs whereas aspirin decreased them even at low concentrations which are clinically relevant. Moreover, through the proteomics, it was confirmed that the toxicity of aspirin to NSCs might be associated with the alteration of several intracellular proteins. Taken together, these results suggest that clopidogrel resinate and clopidogrel bisulfate are safe but aspirin could be toxic to NSCs. Therefore, when these antiplatelet agents are prescribed over the long-term, the finding that aspirin could be toxic to NSCs should be considered.

Formulation of venlafaxine for once daily administration using polymeric material hybrids.

OBJECTIVE: Controlled release venlafaxine for once daily administration. METHODS: Drug resin complexation followed by polymer encapsulation. A 4(1).2(1) factorial design was used to study the effect of polymer type and core: coat ratio on the release profile and kinetics. Polymer combinations were tried for optimisation adapting the desIMNCility function. The optimised formula was tested in rabbits against commercial extended release capsules. RESULTS: Poly-epsilon-caprolactone, poly(d, l-lactide-co-glycolide) ester and poly(d, l-lactide) ester polymers were more efficient in lowering the release rate and the initial burst release than Eudragit(®)RS100. Encapsulation at 1:1 ratio ensured complete coats and drug release sustainment. Formula prepared using 50:50 PLA/Eudragit at 1:1 ratio sustained the drug release up to 24 h with low burst release. This formula had higher venlafaxine absorption in rabbits compared to the commercial capsules. CONCLUSIONS: The optimised formula is superior to the available once-daily trials regarding enhanced bioavailability, dosage form versatility and ease of scaling up.

Reused cyclodextrin as a new way to deliver and enhance drug loading onto ion exchange resin.

CONTEXT: Cyclodextrins could improve drug solubility and drug loading onto ion exchange resins. Moreover, the remaining cyclodextrin in the solution might be reused for drug solubility enhancement and drug loading onto resin. OBJECTIVES: To investigate the application of fresh and reused cyclodextrin to improve drug solubility and drug loading onto resin. METHODS: The inclusion complexes were prepared and characterized using ß-cyclodextrin (ßCD) and 2-hydroxypropyl-ß-cyclodextrin (HPßCD). The drug solution was loaded onto resin with and without cyclodextrin. Then, the remaining cyclodextrin was reused for the complex and the drug loading process. RESULTS AND DISCUSSION: Improved drug solubility was observed when using cyclodextrins. The complex was successfully formed with 1:1 stoichiometry. The increase in drug solubility with cyclodextrins improved drug loading onto resin. The cyclodextrins delivered drug to bind with resin, forming resinate, and did not bind with the resinate themselves, which was confirmed by quantification of the amount of cyclodextrin in drug loading solution before and after drug loading process. Therefore, cyclodextrins were available to reuse for drug loading without affecting the percentage of drug loading. CONCLUSIONS: Reused cyclodextrin is a novel way to deliver and enhance drug loading onto resin for development of an ion exchange-based drug delivery system.

Pine-Oil-Derived Sodium Resinate Inhibits Growth and Acid Production of Streptococcus mutans In Vitro.

S. mutans is a key pathogen in dental caries initiation and progression. It promotes oral biofilm dysbiosis and biofilm acidification. Sodium resinate is a salt of pine-oil-derived resin which has antimicrobial properties. Pine-oil-derived resin consists of terpenes, diterpenes, and abietic acids. The aim of this study was to determine the effects of pine (Pinus sylvestris) oil resinate (RS) on growth and acid production of cariogenic S. mutans strains in planktonic form and biofilm. The S. mutans type strain NCTC10449 and clinical isolate CI2366 were grown on 96-well plates for testing of RS effects on growth and biofilm formation, and on plates with integrated pH-sensitive optical ensors for real-time measurements of the effects of RS on bacterial acid production. We found that even short-time exposure to RS inhibits the growth and acid production of S. mutans in the planktonic phase and biofilms. In addition, RS was able to penetrate the biofilm matrix and reduce acid production inside S. mutans biofilm. RS thus shows potential as a novel antibacterial agent against cariogenic bacteria in biofilm.

Effect of different cross-linking methods and processing parameters on drug release from hydrogel beads.

The purpose of this work was to evaluate different methods of cross-linking for developing diltiazem-resin complex loaded carboxymethyl xanthan gum (CMXG) hydrogel beads to achieve highest possible drug entrapment and extended release for effective cardio-protection. The hydrogel beads were prepared by ionic cross-linking and dual cross-linking using simultaneous (SIM) and sequential (SEQ) methods. Among the three methods, SEQ method produced smaller sized beads having higher drug entrapment efficacy and prolonged release characteristics as evidenced from mean dissolution time and diffusion coefficient of drug. Keeping the concentration of ionic cross-linker constant, increase in the amount of covalent cross-linker and cross-linking time decreased the drug release. Higher release of the drug in acid solution was attributed to the higher solubility of the basic drug and higher swelling of the matrices in acid solution. Comparison of FTIR spectra, drug content and dissolution profiles indicated that the drug was stable in the beads when kept under stress condition up to 3 months. In conclusion, the sequential method was found superior for producing CMXG hydrogel beads as a prolonged release delivery device in cardiovascular diseases.

Ion-exchange resin complexation: Masking the bitter taste of cefuroxime axetil / Complejación de la resina de intercambio de iones: enmascaramiento del sabor amargo de cefuroxime acetil

OBJECTIVE: the purpose of this research was to formulate taste masked complexes of cefuroxime axetil and to evaluate them for taste, drug loading and characterized by FTIR, XRD. Tablets were formulated of selected batches and evaluated for drug release and physical parameters. METHODS: complexation technique is used to prepare complexes of drug where ion exchange resins such as Indion® 214, Indion® 234 and Indion® 414 were used with a drug-resin ratio of 1:0.5, 1:1, 1:2. The drug resinates were characterized by Infrared Spectroscopy, DSC and X-Ray Diffraction pattern and evaluated for drug loading and taste. Direct compression method was used to formulate tablets. In vitro dissolution was carried out using USP II apparatus. RESULT: potential taste masking increased with increasing concentration of resin. Indion® 214 resin showed better taste masking effect as compared to Indion® 234 and Indion® 414. Percent of drug loading was maximum at drug : resin ratio of 1:1, after that it decreased. Prolonged (upto 5 h) and slow drug release was observed with resin 214 at higher concentration. CONCLUSIONS: out of three resins chosen, Indion® 214 at higher concentration exhibit excellent taste masking as well as sustained drug release action.

OBJETIVO: el objetivo de esta investigación fue formular los complejos con sabor amargo de cefuroxime acetil y evaluarlos por sabor, carga medicamentosa y caracterización por FTIR, XRD. Las tabletas fueron formuladas a partir de lotes seleccionados y evaluados en busca de la liberación medicamentosa y parámetros físicos. MÉTODOS: la técnica de complejación se utilizó para preparar complejos farmacológicos donde las resinas de intercambio iónico como Indion® 214, Indion® 234 y el Indion® 414 se emplearon a una proporción resina-medicamento de 1:0.5, 1:1, 1:2. Los resinados medicamentosos fueron caracterizados mediante espectroscopia infrarroja, DSC y el patrón de difracción-rayos-X, y evaluados para determinar la carga medicamentosa y el sabor. El método de compresión directa fue empleado para formular las tabletas. Se efectuó una disolución in vitro utilizando el equipo USP II. RESULTADOS: el posible enmascaramiento del sabor aumentó con la creciente concentración de resina. La resina Indion® 214 mostró el mejor enmascaramiento del gusto amargo en comparación con Indion® 234 e Indion® 414. El porcentaje de carga medicamentosa fue máximo en el fármaco: proporción de la resina 1:1, después disminuyó. Se observó una liberación medicamentosa prolongada (hasta 5 h) y lenta con la resina 214 a una mayor concentración. CONCLUSIONES: de las 3 resinas escogidas, Indion®214 a una mayor concentración muestra un excelente enmascaramiento del sabor así como una mantenida acción liberadora del fármaco.