Ion-exchange Resin Complexes Research Articles

Preparation of berberine hydrochloride ion-exchange resin complex by β-cyclodextrin inclusion

In this study, berberine hydrochloride was combined with ion exchange resin to mask the unpleasant taste of berberine hydrochloride. The research uncovered the equation of berberine hydrochloride solubility in different β-cyclodextrin concentrations at different temperatures, providing a foundation for selecting binding parameters. The effects of various factors on the reaction process were then investigated. Following that, the characteristics and taste evaluation were studied to verify the formation. at last, the in vitro release studies of chosen complexes were determined in solution mediums with pH values of 1.0, 4.5, and 6.8. The results revealed that Amberlite IRP69, which has a higher drug availability and a better taste-masking effect, was selected as the drug carrier. The optimal combined conditions are that the β-cyclodextrin concentration is 0.06 mol·L−1, the temperature is 65 °C, and the berberine hydrochloride concentration is 15 mg·mL−1. Finally, in vitro release experiments of berberine hydrochloride and Amberlite IRP69 complex showed that the drug could be released more than 90% in a medium with pH values of 1.0, 4.5, and 6.8. The research provided a method for preparing the berberine hydrochloride and resin complex, and the well-tasting complex was successfully prepared.

FORMULATION AND EVALUATION OF FAST DISSOLVING TABLET OF LEVOCETIRIZINE DIHYDROCHLORIDE AND MONTELUKAST SODIUM

Introduction: Fast disintegrating tablets (FDTs) have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical industry. Objective: The aim of the present study was to formulate fast-dissolving tablets of Levocetirizine dihydrochloride (LEV) and Montelukastsodium (MON) by direct compression method. Material And Methods: An attempt was made to mask the bitter taste of Levocetirizine by preparing an ion exchange resin complex by a batch method using Kyron T-104. The tablets were prepared using mannitol, microcrystalline cellulose as diluents, and croscarmellose sodium and crospovidone as super disintegrants. Parameters like a drug: resin ratio, pH & swelling time were successfully optimized to prepare the drug resin complex. The fast-dissolving tablets were characterized for various pre and post-compression parameters along with disintegration time, content uniformity, wetting time, in-vitro drug release, in vivo taste evaluation, and compatibility studies. Result and Discussion: The tablets prepared by direct compression method possess a hardness of 3.4 to 3.6 Kg/cm², percentage friability of 0.65 to 0.80, in vitro disintegration time of 29.82 to 51.7 seconds, and wetting time of 20.4 to 46.8 seconds. The formulation (F4)containing crospovidone and croscarmellose sodium in 2:4 ratios showed better disintegration time and more than 99% drug release within 6 minutes. Comparative taste evaluation proves the palatability of formulated tablets. Results of stability studies were also found in acceptable limits. Conclusion: The prepared orodispersible tablets disintegrate within seconds without the need for water and enhance absorption; thismay lead to increased bioavailability of LEV as well as MON.

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.

Study on the Complexation and Release Mechanism of Methylphenidate Hydrochloride Ion Exchange Resin Complex

Since the advent of ion exchange resin, it has been widely used in many fields, including drug delivery systems. The drug binds to the resin through an exchange reaction to form a drug–resin complex, which can gradually release drugs through the exchange of physiological ions in the gastrointestinal tract, to realize functions such as taste masking and regulating release. In this study, the complexes of methylphenidate hydrochloride and Amberlite IRP69 were prepared and evaluated to explore the mechanism of complexation, influencing factors and release mechanism at a molecular level. Firstly, with the properties of the selected complexes, molecular dynamics simulation was innovatively used to find that the intermolecular interaction between drug molecules and ion exchange resin molecules is mainly caused by the stacking effect of π and salt bridges. Secondly, with the drug loading status as an indicator, the factors affecting the compounding process of the drug and resin were explored. Finally, the release mechanism of the drug–resin complex was studied by mathematical model fitting. In summary, a variety of methods were used to study the mechanism of complexation and release between drug and resin, providing a theoretical basis for promoting the marketing of ion−exchange resin−mediated oral preparations.

Preparation and Investigation of Gastro-Retentive Mucoadhesive Microspheres of Clarithromycin-Resin Complex

Introduction: Helicobacter pylori infection is strongly associated with chronic gastritis and duodenal ulcers which can benefit from gastroretentive delivery of clarithromycin. Objectives: The objective of this study was to investigate mucoadhesive microspheres of the antibiotic – resin complex for gastro-retention, thereby increasing the local effective concentrations of clarithromycin. Methods: Clarithromycin-resin complex granules were coated with the mucoadhesive polymers, Carbopol 934 and Polycarbophil in different ratios of 1:1, 1:2, 1:3 and 1:4 by solvent evaporation method. Prepared microspheres were subjected to characterization for particle size and shape, drug content, in vitro mucoadhesion, in vitro drug release and in vivo gastric residence time in albino rats. Results and Discussion: Particle sizes of the microspheres were found to be in the range of 83 μm-87μm. Scanning electron microscopic images of the formulation showed spherical particles with almost smooth surface morphology for carbopol microspheres. Formulations with both polymers showed mucoadhesion for a period of more than 6 hr. In vitro drug release using the USP dissolution test apparatus appeared to follow first order kinetics. Fluorescence imaging of histo-pathological slides of rats gastric and intestinal mucosa reveal that gastric residence time was found to be longer than 6 h for carbopol microspheres and at least 4 h in the case of polycarbophil microspheres. Conclusion: Carbopol coated microspheres of ion exchange resin complexes of clarithromycin for the gastro-retentive delivery of clarithromycin can be a promising alternative to the conventional oral solid dosage forms in the control of H. pylori induced chronic gastritis or duodenal ulcers.

Application of PLGA-ion exchange resin microcapsules of sulfasalazine ‎for embolization therapy

ABSTRACT
 Objective: This work involves preparation and evaluation (in vitro/ in vivo) of microcapsules containing sulfasalazine- ion exchange resin complex (resinate) to induce emboli for treatment of solid cancer.
 Methods: The drug resin complex (resinate) had been optimized by using drug: resin ratio (1:8), by suspending the resin in sulfasalazine aqueous solution with at 400 rpm for 120 minutes at 50 ºC. For controlling the release of drug, microencapsulation for the resinate was applied where 21 formulas with different resinate: PLGA ratios 2:1, 1:1, 1:2 were prepared by solvent evaporation method to study the effect of different variables including resinate: polymer ratio, stirring speed, effect of temperature and aqueous phase volume on microencapsulation efficiency and percent yield.
 Results: The in-vitro release study for the prepared resinate, which had 72% entrapment efficiency, showed 80.992 % of drug released within 15 minutes and the release continued until 99.83% within 75 minutes formula was found to be F19 had 76.70% encapsulation efficiency and 89.40% percent yield. The in vitro release study for selected formula showed that 32% of drug released within 1hour and 78% of drug released within 20 days and the release continued up to 96% within 45 days indicating a controlled release manner with spherical microcapsule of 595µm. The preliminary in vivo work using rabbits showed instant occlusion of the central auricular artery of the rabbit ear leading to ischemia within 3 days that continued to the end of study period
 Conclusion: This work show the suitability of microcapsules size to prevent blood flow and forming embolization with controlling release of the drug that may treat the solid tumor.

Application of PLGA-ion exchange resin microcapsules of sulfasalazine ‎for embolization therapy

Objective: This work involves preparation and evaluation (in vitro/ in vivo) of microcapsules containing sulfasalazine- ion exchange resin complex (resinate) to induce emboli for treatment of solid cancer. Methods: The drug resin complex (resinate) had been optimized by using drug: resin ratio (1:8), by suspending the resin in sulfasalazine aqueous solution with at 400 rpm for 120 minutes at 50 ºC. For controlling the release of drug, microencapsulation for the resinate was applied where 21 formulas with different resinate: PLGA ratios 2:1, 1:1, 1:2 were prepared by solvent evaporation method to study the effect of different variables including resinate: polymer ratio, stirring speed, effect of temperature and aqueous phase volume on microencapsulation efficiency and percent yield. Results: The in-vitro release study for the prepared resinate, which had 72% entrapment efficiency, showed 80.992 % of drug released within 15 minutes and the release continued until 99.83% within 75 minutes formula was found to be F19 had 76.70% encapsulation efficiency and 89.40% percent yield. The in vitro release study for selected formula showed that 32% of drug released within 1hour and 78% of drug released within 20 days and the release continued up to 96% within 45 days indicating a controlled release manner with spherical microcapsule of 595µm. The preliminary in vivo work using rabbits showed instant occlusion of the central auricular artery of the rabbit ear leading to ischemia within 3 days that continued to the end of study period Conclusion: This work show the suitability of microcapsules size to prevent blood flow and forming embolization with controlling release of the drug that may treat the solid tumor.

Preparation and characterization of Starch–Urea–Borate: A new floating polymer

In recent years considerable attention has been focused on the development of new drug delivery systems known as controlled release drug delivery systems. Such interest is based largely on the fact that the controlled release products have established and retained place in the market based on their uniqueness and their clinical advantages in the practices of medicine. The major types of controlled release systems include matrix tablets, floating tablets, swellable tablets, coated beads, microcapsules and microspheres, mucoadhesive systems, ion exchange resin complexes, osmotic pressure controlled release systems, transdermal systems etc. The principle of floating tablets offers a simple and practical approach to achieve increased gastric residence time to enhance the bioavailability and to obtain controlled release. Floating tablets are designed based on gas generating principle. Design of floating tablets needs a strong matrix forming polymer. Several polymers such as various viscosity grades of hydroxypropylmethyl cellulose (HPMC), Carbopol 934P, Eudragit RL, calcium alginate, chitosan, xanthan gum, guar gum, ethyl cellulose etc., have been used in the design of floating tablets of various active pharmaceutical ingredients (APIs). Though these polymers are available for floating tablets, there is a continued need to develop new, effective and efficient polymers for controlled release floating tablets.The overall objective of the investigation is to develop new, efficient and safe polymer as floating matrix former for floating systems.
 Keywords: Floating, Matrix, Polymers, Starch-urea-borate.

Diclofenac sodium ion exchange resin complex loaded melt cast films for sustained release ocular delivery

Purpose: The goal of the present study is to develop polymeric matrix films loaded with a combination of free diclofenac sodium (DFSfree) and DFS:Ion exchange resin complexes (DFS:IR) for immediate and sustained release profiles, respectively.Methods: Effect of ratio of DFS and IR on the DFS:IR complexation efficiency was studied using batch processing. DFS:IR complex, DFSfree, or a combination of DFSfree + DFS:IR loaded matrix films were prepared by melt-cast technology. DFS content was 20% w/w in these matrix films. In vitro transcorneal permeability from the film formulations were compared against DFS solution, using a side-by-side diffusion apparatus, over a 6 h period. Ocular disposition of DFS from the solution, films and corresponding suspensions were evaluated in conscious New Zealand albino rabbits, 4 h and 8 h post-topical administration. All in vivo studies were carried out as per the University of Mississippi IACUC approved protocol.Results: Complexation efficiency of DFS:IR was found to be 99% with a 1:1 ratio of DFS:IR. DFS release from DFS:IR suspension and the film were best-fit to a Higuchi model. In vitro transcorneal flux with the DFSfree + DFS:IR(1:1)(1 + 1) was twice that of only DFS:IR(1:1) film. In vivo, DFS solution and DFS:IR(1:1) suspension formulations were not able to maintain therapeutic DFS levels in the aqueous humor (AH). Both DFSfree and DFSfree + DFS:IR(1:1)(3 + 1) loaded matrix films were able to achieve and maintain high DFS concentrations in the AH, but elimination of DFS from the ocular tissues was much faster with the DFSfree formulation.Conclusion: DFSfree + DFS:IR combination loaded matrix films were able to deliver and maintain therapeutic DFS concentrations in the anterior ocular chamber for up to 8 h. Thus, free drug/IR complex loaded matrix films could be a potential topical ocular delivery platform for achieving immediate and sustained release characteristics.

Modified Release of Metformin Hydrochloride using Ion Exchange Resin Complex in Floating Mucoadhesive Tablets

Background: Metformin hydrochloride (HCl) is an oral antihyperglycemic drug used in the management of type 2 diabetes. Metformin HCl is not chemically or pharmacologically related to any other classes of oral antihyperglycemic agents and very successfully used as drug of first choice. It has 50-60% oral bioavailability.It is believed to be predominantly absorbed in the upper part of the intestine, and estimated time for its complete absorption is approximately 6 h. Clinical trials with metformin have demonstrated decreased bioavailability at higher doses, suggesting saturable intestinal absorption. There is need and scope to increase oral bioavailability of metformin HCl. These details led to an idea of development of SR tablet with more gastric/duodenum retention and was designed as SR tablet using ion exchange principle in floating, mucoadhesive matrix. Aim: The objective of this research was to formulate floating mucoadhesive tablet of metformin HCl in complex with ion exchange resin, for the therapeutic dose of 250 mg. Materials and Medhods: Metformin HCl being cationic drug can be complexed with cation exchange resin like indion 244.This study began with formulation and optimization of drug-resin complex (DRC). Various parameters like the use of batch and column process, complexation time, temperature, and pH were studied and optimized. DRC was characterized by infrared spectroscopy and X-ray diffraction pattern. The efficient drug loading was evident in a batch process using activated indion 244 with a drug-resin ratio of 1:1. Drug complexation enhanced with pH 3.5, temperature 60°C. Infrared spectroscopy revealed complexation of: −NH group of the drug with −C=O stretching of aryl acids of indion 244. Optimized DRC obtained was amorphous in nature. This DRC was put into tablet which could sustain the release of metformin in the favorable region of gastric pH because of inherent slow release from DRC along with a matrix of hydroxylpropylmethylcellulose (HPMC) K100M and Carbopol 974P. HPMC K100M along with sodium bicarbonate made this tablet float and Carbopol 974P gave the additional property of mucoadhesion. The quantity of carbopol optimized first and quantity of HPMC and carbopol using 32 factorial design. Results: The tablets were evaluated for hardness, thickness, friability, drug content, weight variation, floating lag time, floating time, mucoadhesive strength, and in vitro drug release. Tablets thus formulated (Batch M-3) provided sustained release using floating and mucoadhesion approaches over a period of 12 h. The project is open for in vivo studies. Conclusions: Metformin HCl (250 mg) table as drug resin complex in mucoadhesive floating matrix can provide advantage for early cases of diabetics. Floating mucoadhesive tablet having metformin HCl complexed with indion 244 is not available in the market and not yet reported in research paper as per literature survey. This could be one of the attempts to increase the oral bioavailability of metformin HCl.

Conditioned taste aversion in the grey fox (Pseudalopex griseus), in Southern Argentine Patagonia

Attempts to control cougar (Puma concolor) and culpeo fox (Pseudalopex culpaeus) populations in Patagonia through poisoning, negatively affects grey foxes (Pseudalopex griseus) and many other non-target species. It is therefore advisable to develop selective predator control methods. Among a wide range of potential methods, are those based on manipulating the behaviour of non-target species. Conditioned taste aversion (CTA) develops when an animal associates taste with subsequent illness, and, after recovery, avoids the referent taste. Food aversions can be potentially useful in efforts to reduce losses of non-target species when lethal baits are distributed to control other predators. We evaluated two ways to add the aversion agent Levamisole hydrochloride to a bait to generate CTA in grey foxes. We established one control (without Levamisole) and two treatments: plain Levamisole and an ion-exchange resin complex (resinate: Amberlite® IRP-64) aiming to mask the taste of Levamisole. Foxes that ate plain Levamisole baits, ate fewer baits than those in control (26.7% plain Levamisole baits vs. 83.3% untreated baits, P=0.002) even after plain Levamisole was no longer present in the baits (40.0% vs. 86.6% untreated baits, treatment and control respectively, P=0.007). Foxes that ate Levamisole resinate baits, also ate fewer baits than those in control (50.0% Levamisole resinate baits vs. 83.3% untreated baits, P=0.043) but then resumed consumption when baits no longer contained the Levamisole resinate (73.3% vs. 86.6% untreated baits, treatment and control respectively, P=0.329). Thus, foxes that failed to detect the plain Levamisole in baits acquired CTA to the bait. Contrary to our expectations, foxes detected the Levamisole resinate, associated illness with it and so resumed eating baits as soon as the resinate was withdrawn. Additionally, in the control, where foxes were familiar with untreated “safe” baits, we repeated the treatment with Levamisole resinate baits to test latent inhibition (decrement in conditioning to a stimulus as a result of its prior exposure). We found that treated bait consumption did not decrease as before, during a similar number of days (76.6% Levamisole resinate baits vs. 83.3% untreated baits, P=0.631), suggesting that latent inhibition prevented development of CTA within our experimental time period. CTA induced among grey foxes that consume plain Levamisole baits might spare them from being poisoned in attempts to control other species of predators.

Fast Disintegrating Combination Tablet of Taste Masked Levocetrizine Dihydrochloride and Montelukast Sodium: Formulation Design, Development, and Characterization.

The aim of this study was to prepare fast disintegrating combination tablet of taste masked Levocetrizine dihydrochloride and Montelukast sodium by using direct compression method. To prevent bitter taste and unacceptable odour of the Levocetrizine dihydrochloride drug, the drug was taste masked with ion exchange resins like Kyron-T-104 and Tulsion-412. Among the two resins, Kyron-T-104 was selected for further studies because of high drug loading capacity, low cost, and better drug release profile. An ion exchange resin complex was prepared by the batch technique and various parameters; namely, resin activation, drug: resin ratio, pH, temperature, and stirring time, and swelling time were optimized to successfully formulate the tasteless drug resin complex (DRC). The tablets were prepared using microcrystalline cellulose (MCC) PH 102 as diluent along with crospovidone (CP), croscarmellose sodium (CCM), and sodium starch glycolate (SSG) as a superdisintegrants. The tablets were evaluated for weight variation, hardness, friability, wetting time, water absorption ratio, disintegration time (DT), and dissolution study and it was concluded that the tablet formulation prepared with 2% SSG + CCS showed better disintegration time in comparison with other formulation and good drug release. The stability studies were carried out for the optimized batch for three months and it showed acceptable results.

Effect of Curing and Compression Process on the Drug Release of Coated Ion-Exchange Resin Complexes

Ion exchange resins can be one of the good carriers for sustained drug release. However, the sustained release may not be enough only with themselves and hence film coating with rate controlling polymers can be applied to have a further effect on the drug release. Due to the environmental and economic issues of organic solvent for the polymer coating, aqueous polymeric systems were selected to develop dosage forms. Among the many aqueous polymeric dispersions for the film coating, EC(ethylcellulose) based polymers such as Aquacoat(R) ECD and Surelease(R) were evaluated. A fluid-bed coating was applied as a processing method. The drug release rate was quite dependent on the coating level so the release rate could be modified easily by changing different levels of the coating. The drug release rate in the Aquacoat (R) coated resin particles was strongly dependent on curing, which is a thermal treatment to make homogeneous films and circumvent drug release changes during storage. After dissolution test using the compressed tablets in which the coated resin particles are contained, inhomogeneous coating and even pores could be observed showing that the mechanical properties of EC were not resistant to granulation and compaction process. However, when tablets were prepared in different batches, the release profiles were almost identical showing the feasibility of the coated resin particle as incorporated into the tablet formulation.

Pharmacokinetics of a novel liquid controlled release codeine formulation

Codeine is an important opioid anti-tussive agent whose short half-life (2.9 ± 0.7 h) requires that it be administered at 4-h intervals when formulated as a simple aqueous solution. Liquid controlled release codeine formulations such as an older Codipertussin® formulation, which contained codeine bound to an ion exchange resin and coated with a retardant polymer, achieved an equivalent bioavailability when administered every 12 h. An accompanying paper described the development and in vitro characterization of a novel Codipertussin® formulation containing a non-coated codeine:ion exchange resin (Amberlite IR 69 F) complex. In this study, the bioavailability of codeine from this new liquid controlled release formulation was investigated in an open label, single center, randomized, steady-state, cross-over study in healthy male volunteers. Participants received either 69.7 mg codeine as the controlled release liquid form every 12 h or 23.2 mg codeine in solution every 4 h. Controlled release from the suspension of beads protracted the apparent mean half life of codeine from 3.2 h to 8.2 h, while the mean AUC0–12 h was unchanged. In vivo codeine release profiles were further derived by the numerical deconvolution method, using the data from the drug solution as weighting function for the body system. Comparison of the data obtained with the in vitro release data presented in our earlier work showed an acceptable in vitro–in vivo correlation, which was described as in vitro–in vivo relationship, indicating the power of the in vitro method to predict in vivo pharmacokinetic behavior.

Ion-exchange resins as drug delivery carriers

There are many reports in the literature referring to the utilization of drug bound to ion-exchange resin (drug–resinate), especially in the drug delivery area. Ion-exchange resin complexes, which can be prepared from both acidic and basic drugs, have been widely studied and marketed. Salts of cationic and anionic exchange resins are insoluble complexes in which drug release results from exchange of bound drug ions by ions normally present in body fluids. Resins used are polymers that contain appropriately substituted acidic groups, such as carboxylic and sulfonic for cation exchangers; or basic groups, such as quaternary ammonium group for anion exchangers. Variables relating to the resin are the exchange capacity; degree of cross-linking, which determines the permeability of the resin, its swelling potential, and the access of the exchange sites to the drug ion; the effective pKa of the exchanging group, which determines the exchange affinity; and the resin particle size, which controls accessibility to the exchange ions. In this review, the properties of ion-exchange resins, selection of drugs that lend themselves to such an approach, selection of the appropriate resin, preparation of drug–resinate, evaluation of drug release, recent developments of drug–resinates, and applications are discussed. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3886–3902, 2009

A simple and large-scale strategy for the preparation of Ag nanoparticles supported onresin-derived carbon and their antibacterial properties

A simple strategy was developed for preparing stable Ag nanoparticles supported on carbon by carbonizingAg+/acrylic acid type ion-exchange resin complexes underN2 atmosphere. The products were characterized by x-ray powder diffraction (XRD), scanningelectron microscopy (SEM), transmission electron microscopy (TEM) and UV–visibleabsorption spectroscopy. The results indicated that the Ag nanoparticles were welldispersed on the surface of carbon, and their size could be regulated by tuningthe carbonization temperature. The antibacterial assay showed that the Ag/Ccomposites possess good antibacterial properties that are determined largely by the Agparticle size. Furthermore, the composites are very stable and they do not showobviously change even after storing at ambient conditions for more than one year.

Studies of the Development of Optical Fiber Sensors for Biochemical Analysis

An optical fiber sensor utilizing Thymol blue and an ion-exchange resin complex in a cellulose acetate membrane was developed. By monitoring several different chromophores of Thymol blue, the sensor could measure the pH of the solution from 1.0 to 12.0 with good reproducibility. An optical fiber glucose sensor utilizing a cellulose acetate membrane containing glucose oxidase, 2,7-diaminofluorene dihydrochloride, and sodium N-(3-sulfopropyl)-3,3',5,5'-tetramethylbenzidine was developed. Reflectance changes at 580 nm were large enough to trace changes in glucose concentration in physiological saline solution.

Drug loading and release properties of ion-exchange resin complexes as a drug delivery matrix

Complexes of ion-exchange resins and dextromethorphan (DM), a model drug, were prepared using different methods including a batch and a column method with different functional groups, ion-exchange capacity, degree of crosslinking, and resin particle size. Drug loading efficiency, release profiles, and scanning electron micrographs were also investigated. Most of the functional groups of resins were loaded with DM after the completion of a double batch method and it was recommended for drug loading into the ion-exchange resin. Using a column method, drug loading could be monitored by simply measuring changes in the pH of the reaction medium since as complex formation reached completion, the pH returned to the initial pH of the eluent due to the limited amount of functional groups available for the exchange. DM could be loaded up to the ratio of 3 (drug): 1 (resin), depending on the physicochemical properties of the resin. As the crosslinking ratio and particle size increased, the drug loading and release rate decreased due to the reduced effective diffusion coefficient and surface area. Assuming that the resin particles are uniform spheres of radius r, release mechanism was evaluated using plots of a Bt − t relationship, where B (= π 2 D i / r 2) and t are the rate constant and time, respectively. D i represents the effective diffusion coefficient of DM inside the resin. The Bt − t plots displayed a straight line indicating that the diffusion of DM in the resin matrix is the rate-controlling step.

Development of sustained release fast-disintegrating tablets using various polymer-coated ion-exchange resin complexes

Complex formation between drugs and ion-exchange resins was investigated and the effects of coating by various aqueous polymeric dispersions on the complexes were evaluated for developing new sustained-release fast-disintegrating tablets (FDTs). Complexes of ion-exchange resin and dextromethorphan, a model drug, were prepared using different particle sizes of the resins. Aqueous colloidal dispersions of ethylcellulose (EC) and poly(vinyl acetate) (Kollicoat ® SR30D) were used for fluid-bed coating. Based on drug loading, release profiles, and scanning electron microscopy (SEM) images, the coated particles were granulated with suitable tablet excipients and then compressed into the tablets. Drug release profiles and SEM pictures were compared before and after the manufacturing processes. As the particle size of resins increased, the drug loading and release rate decreased due to the reduced effective diffusion coefficient and surface area. Higher coating level decreased the release rate further. In contrast to EC, Kollicoat ® SR30D coated particles could be compressed into tablets without any rupture or cracks on the coating since the mechanical properties of the polymer was more resistant to the manufacturing processes. This resulted in no significant changes in release rates. SEM showed the mechanical strength of the polymers affected the morphological change after compression. When the drug release profiles were applied into Boyd model and Higuchi equation, the linear relationship was observed, indicating that the diffusion within the resin matrix is the rate-controlling step.

Drug Release Properties of Polymer Coated Ion-Exchange Resin Complexes: Experimental and Theoretical Evaluation

Although ion-exchange resins have been used widely as drug delivery systems, their exact release kinetics has not been reported yet. Usually only the rate-limiting step has been taken into account and the rest of the steps have been ignored as instantaneous processes. To investigate the exact release kinetics of polymer-coated drug/ion-exchange resin complexes for sustained drug delivery, the results of new mathematical modeling were compared with experimental results. Drug/resin complexes with a model drug, dextromethorphan, were prepared and used as cores for fluid-bed coating. An aqueous colloidal dispersion of poly(vinyl acetate) was applied for the coating. A comprehensive mathematical model was developed using a mechanistic approach by considering diffusion, swelling, and ion-exchange processes solved by numerical techniques. The rate-limiting factor of the uncoated resin particles was diffusion through the core matrix. Similarly, in the coated particles the rate-limiting factor was diffusion through the coating membrane. The mathematical model has captured the phenomena observed during experimental evaluations and the release dynamics from uncoated and coated (at different coat levels) particles were predicted accurately (maximum RMSE 2.4%). The mathematical model is a useful tool to theoretically evaluate the drug release properties from coated ion-exchange complexes thus can be used for design purposes.