Drug Resin Research Articles

Central Composite Designed Taste Masked Ion Exchange Resinates for Development of Azithromycin Dispersible Tablets

Purpose : The purpose of the present investigation was to formulate taste masked dispersible tablets of azithromycin using complexation by ion exchange resin applying the central composite design. Methodology : The basic methodology behind the present work was the application of ion exchange resin complexation for masking the bitter taste of azithromycin. The central composite design (CCD) was applied to study the effect of two critical factors i.e. swelling time (X 1 ) and stirring time (X 2 ) on percent drug complexed and cumulative percentage drug release. ANOVA was applied to percent drug complexed and cumulative percentage drug release to study the tting and the signicance of the model. The drug resinate was nally formulated into dispersible tablets by direct compression method. Findings : The drug resin ratio of 1:3 and pH 6 were found to have maximum drug loading onto the resin (Tulsion 335). The maximum drug release was found at high values of swelling and stirring time. The techniques of differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) clearly indicated the formation of drug resin complex. Further, the formulated tablets were found to be within the pharmacopoeial limits. Originality : The present work is a novel attempt to prepare optimized taste masked formulation of extremely bitter drug azithromycin to overcome the problem of swallowing conventional tablets in case of paediatric patients. Conclusion: The technique of ion exchange resin complexation was successfully applied to prepare the taste masked azithromycin dispersible tablets. Data revealed that the developed dispersible tablets showed better taste prole when compared with the marketed formulation and were found to be stable.

ION EXCHANGE RESINS AND THEIR APPLICATIONS

Ion exchange resins are cross-linked water insoluble polymer-carrying, ionisable functional groups. IER have received considerable attention from pharmaceutical scientists because of their versatile properties as drug delivery vehicles. Research over the last few years has revealed that IER are equally suitable for drug delivery technologies, including controlled release, transdermal, nasal, topical and taste masking. The major drawback of sustained release of extended release or extended release is dose dumping, resulting in increased risk of toxicity. The use of IER has occupied an important place in the development of controlled- or sustained-release systems because of their better drug-retaining properties and prevention of dose dumping. Synthetic ion exchange resins have been used in pharmacy and medicine for taste masking or controlled release of drug. Drug resin complexation converts drug to amorphous form leading to improved drug dissolution. Several studies have reported the use of IER for drug delivery at the desired site of action. Sulfonated and carboxylic resins with a polystyrene backbone are most widely used in clinical medicine.

Delivery of Repaglinide-Cholestyramine Complex Loaded Ethylcellulose Microspheres to Gastric Mucosa for Effective Management of Type-2 Diabetes Mellitus

The main aim of this work is to develop and thoroughly evaluate resin-based multiparticles of repaglinide for effective management of type-2 diabetes mellitus. Repaglinide was complexed with cholestyramine resin; later the resin complexed drug was encapsulated in ethylcellulose microspheres. The microspheres were characterized for micromeritic properties, SEM analysis, entrapment efficiency, percentage yield, IR spectroscopy, buoyancy behaviour and in vitro drug release in simulated gastric fluid. Microparticles showed regular shape and spherical morphology with entrapment efficiency in the range 51-69%. Differential scanning calorimetry confirmed that there was no chemical interaction between the polymer and the drug. Resin-based microspheres showed good buoyancy behaviour (P < 0.05) due to the presence of bicarbonate ions and sustained release compared to plain drug microspheres (P < 0.05). Finally, the effectiveness of the formulations was evaluated in vivo for blood glucose lowering effect in both normal and streptozotocin-induced diabetic rats. Blood glucose lowering effect induced in diabetic rats by the repaglinide- loaded microspheres was significantly greater (P < 0.05) and prolonged (∼8 h) compared to plain drug microspheres. In a nutshell, floating microspheres containing drug resin complex were able to sustain the drug release in an effective manner for prolonged periods of time and proven in vivo effectiveness by reducing blood glucose level for a longer duration.

Preparation and evaluation of orally disintegrating tablets of taste masked phencynonate HCl using ion-exchange resin

This study was intended to design an orally disintegrating tablet (ODT) formulation that can mask the extremely bitter and metallic taste of phencynonate HCl by novel ion-exchange resins. The drug–resin complexes (DRCs) were prepared and characterized by scanning electron microscopy, X-ray powder diffraction and differential scanning calorimetry. In vitro properties (dissolution, wetting time and disintegration time) and in vivo behavior (disintegration time and taste-masking effect) in healthy volunteers of the prepared ODTs were also investigated. The drug was changed from the crystal structure to the amorphous form in the DRC. Compared with commercial tablets, the in vitro and in vivo disintegration of optimized DRC-loaded ODTs with a drug-resin ratio of 1:1 was greatly improved and better palatability with a low bitterness index (0.33) was obtained. The current DRC-loaded ODT could promise a good way to mask the unpleasant taste of certain drugs and accordingly improve the patient compliance.

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.

FORMULATION AND EVALUATION OF TASTE MASKED ORAL SUSPENSION OF CHLOROQUINE PHOSPHATE

The purpose of this research was to mask the intensely bitter taste of Chloroquine phosphate using ion exchange resin and to formulate oral suspension of the taste masked drug. Batch method was used for formation of drug resin complex. Various ion exchange resins such as Doshion P 544 S and Kyron T- 114 were tried to obtained taste masked drug resin complex (DRC). Optimization of drug loading was carried out. With Doshion P 544 S, the drug-resin proportion of 1:4 achieved equilibrium in 5 hours. 96% w/w of drug loading was possible by this method. Complex formation was confirmed by DSC and IR studies. Oral taste masked suspension was prepared using xanthum gum at various concentrations 0.1%, 0.2% and 0.4% respectively. CPR 1 and CPR 2 batches showed satisfactory assay result that is it fulfills the official requirements. But physical properties of suspension were not satisfactory. CPR 1 was not easily redispersible and with CPR 2 caking was observed with sedimentation volume of 0.4, hence these batches were rejected. CPR 3 was found to be optimized batch as it showed complied assay results were found to be easily redispersible even after 7 days with no cake formation and sedimentation volume of 0.98. and was evaluated for various parameters such as Colour, pH, Viscosity etc. Thus, successful taste masking and formulation of suspension with taste masked drug especially for pediatric, geriatric, and non cooperative patients.

Design and evaluation of a brinzolamide drug-resin in situ thermosensitive gelling system for sustained ophthalmic drug delivery.

In this study a brinzolamide drug-resin ophthalmic thermosensitive in situ gelling system was developed and evaluated. Brinzolamide was combined with ion exchange resins to prolong the retention time of drugs in the eye and to reduce ocular and systemic side effects. Poloxamer F127 was used as gelling vehicle in combination with carbopol 934P, which acted as a viscosity-enhancing agent. They were prepared using the cold method. The optimized formulation exhibited a sol-gel transition at 33.2±1.1°C with pseudoplastic flow behavior. This formulation was stable and nonirritant to rabbit eyes. In vitro release studies demonstrated diffusion-controlled release of brinzolamide from the combined solutions over a period of 8 h. In vivo evaluation (the elimination of brinzolamide through tears and absorption of brinzolamide in aqueous humor) indicated that the solution combination was better able to retain the drug than commercial preparations. Thus this formulation is safe for ophthalmic use and significantly increases brinzolamide bioavailability in aqueous humor.

ION EXCHANGE RESINS: AN APPROACH TOWARDS TASTE MASKING OF BITTER DRUGS AND SUSTAINED RELEASE FORMULATIONS WITH THEIR PATENTS

The purpose of this review is to cover various aspects related with the use of ion exchange resins for taste masking of bitte r drugs and for formulating sustained release dosage form. Ion exchange resins are wate r insoluble cross - linked polymers containing a salt - forming group at repeating positions on the polymer chain and have the ability to exchange counter - ions within aqueous solutions surrounding them. The bitterness of pharmaceutical medicines plays a critic al role in patient compliance, as the oral administration of bitter drugs is often hampered by their unpleasant taste which l eads to non - compliance and further worsening of diseased condition. One of the popular approaches in the taste masking of bitter dr ugs is based on IER. For taste masking purpose weak cation exchange or weak anion exchange resins are used, depending on the nature of drug. The drug resin complex is absolutely tasteless with no after taste, and at the same time, its bioavailability is no t affected. Sustained release dosage forms are designed to release a drug at a pre determined rate in order to maintain a constant drug concentration for a specific period of time with minimum side effects . The usage of IER during the development of sustai ned release formulations plays a significant role because of their drug retarding properties. In this review also incorporates various pa tents related to taste masking and sustained release formulations using IER.

Oseltamivir Phosphate–Amberlite™ IRP 64 Ionic Complex for Taste Masking: Preparation and Chemometric Evaluation

The objective of the present work was to evaluate and characterize a pediatric-friendly formulation of a bitter tasting drug, oseltamivir phosphate (drug). Amberlite IRP64 (resin) was used to make ionic complexes for masking its bitterness. Complexes of four drug-to-resin ratios, 1:1, 1:2, 1:4, and 1:6 (w/w), were prepared and characterized. At buccal pH of 6.8, drug-resin complexes of 1:1, 1:2, 1:4, and 1:6 ratios released 42.13%, 23.26%, 4.13%, and 14.94%, respectively, of loaded drug after 20 s. However, at stomach pH of 1.2 (0.1 N HCl), 61.96%, 70.18%, 85.88%, and 91.42% of drug was released from the same complexes in 6 min. Near-infrared (NIR) chemical imaging of the complexes showed homogeneous distribution of drug in the resin. Chemometric partial least squares model using NIR data of the drug showed a high correlation between calibration and predicted data (R(2) > 0.998). Overall, these results indicated the complex formation between drug and resin. The pH dependence of drug release from these complexes could minimize drug release in the mouth, whereas immediately releasing it in the stomach. Electronic tongue used to evaluate taste indicated that conductivity taste signals were different from control, suggesting taste masking of the drug.

TASTE MASKING AND FORMULATION DEVELOPEMENT &amp;EVALUATION OF MOUTH DISSOLVING TABLETS OF LEVOCETRIZINE DIHYDROCHLORIDE

Levocetrizine dihydrochloride is the active R (-) enantiomer of cetrizine. It is an orally active and selective H1 receptor antagonist used medically as an Antiallergic. Allergic rhinitis is a symptomatic disorder of the nose induced by inflammation mediated by immunoglobulin E (IgE) in the membrane lining the nose after allergen exposure. Thus formulating Levocetirizine dihydrochloride into a mouth dissolving tablets would provide fast relief. Levocetirizine dihydrochloride is bitter in taste so the Kyron T-134 (ion exchange resin) was used to mask the taste and formulated a mouth dissolving tablets using drug resin complex. Results show that effective taste masking is achieved for Levocetrizine dihydrocloride by preparing drug-resin complex using Kyron T-134. The tablets have evaluated for the drug content, weight variation, and water absorption ratio, wetting time, in vitro disintegration, hardness, friability, thickness uniformity and in-vitro dissolution. The tablets disintegrated in- vitro within 21 to 33 seconds. . The % drug content of tablets in all formulations was found to be between 90-110% which complied with limits established in Indian Pharmacopoeia. In vitro drug release profile of tablets is shown 99% drug release in 10 minutes. The results show that Levocetirizine dihydrochloride is successfully formulated into a mouth dissolving tablet. Key words: Levocetirizine dihydrochloride, Allergic rhinitis, Super disintegrants, Ion exchange resin, Mouth dissolving tablets.

DESIGN, DEVELOPMENT, CHARACTERIZATION AND COMPARISON OF CALCIUM SILICATE AND CHOLESTYRAMINE BASED ELETRIPTAN HYDROBROMIDE FLOATING MICROSPHERES

Studies were carried out to develop, characterize and compare oral floating microspheres for Eletriptan Hydrobromide using Ion exchange resin like Cholestyramine and low density porous carrier like calcium silicate so as to provide extended gastric retention. The prepared resinates were studied for the effect of pH and drug resin ratio on drug loading and is similar with calcium silicate. Both the formulations were evaluated for drug entrapment, in vitro floating behavior, in vivo buoyancy and in vitro drug release studies. Dissolution study of Eletriptan hydrobromide microspheres with both the calcium silicate and cholestyramine was able to sustain the release of the drug. The study suggests that the floating microspheres of Eletriptan hydrobromide provide sustained release over 24 h and also showed in vivo buoyancy for more than 10 h in rabbit.

TASTE MASKING OF DONEPEZIL HYDROCHLORIDE USING DIFFERENT ION EXCHANGE RESINS- A COMPARATIVE STUDY

Taste mainly depends on the physiology, sensitivity and structure of taste buds. It is an important parameter in administering drugs orally. Bitter taste is a major limitation to patient compliance. Donepezil hydrochloride (DH) is a bitter drug used in Alzheimer's disease. Amongst the many techniques for taste masking, using ion exchange resins has been extensively reported. The technique of forming tasteless complexes with bitter drugs involves selection of most appropriate exchanger and optimization of complexing ratio. The aim of the present work was to select the best cationic exchanger amongst Indion 414, Indion 234 and Indion 214. All parameters were optimized to produce drug-loaded tasteless complexes. Complexation was carried out using batch process prior to which, acid-alkali activation was performed to remove adsorbed impurities from the resin bed surface and hence improve loading efficiency. UV-spectrophotometric method was used to determine percent drug loading. The molecular properties of drug resin complexes were studied using Fourier Transform Infra-red Spectroscopy, Differential Scanning Calorimetry and Xray Powder Diffraction which confirmed complexation. Indion 414 was found to give highest drug loading and minimal drug was released from the complex at salivary pH. Key words: Donepezil HCl, Ion exchange resins, Molecular properties, Taste masking

Improvement of drug loading onto ion exchange resin by cyclodextrin inclusion complex

Context: Ion exchange resins have ability to exchange their counter ions for ionized drug in the surrounding medium, yielding “drug resin complex.” Cyclodextrin can be applied for enhancement of drug solubility and stability.Objective: Cyclodextrin inclusion complex of poorly water-soluble NSAIDs, i.e. meloxicam and piroxicam, was characterized and its novel application for improving drug loading onto an anionic exchange resin, i.e. Dowex® 1×2, was investigated.Methods: β-cyclodextrin (β-CD) and hydroxypropyl β-cyclodextrin (HP-β-CD) were used for the preparation of inclusion complex with drugs in solution state at various pH. The inclusion complex was characterized by phase solubility, continuous variation, spectroscopic and electrochemistry methods. Then, the drug with and without cyclodextrin were equilibrated with resin at 1:1 and 1:2 weight ratio of drug and resin.Results and discussion: Solubility of the drugs was found to increase with increasing cyclodextrin concentration and pH. The increased solubility was explained predominantly due to the formation of inclusion complex at low pH and the increased ionization of drug at high pH. According to characterization studies, the inclusion complex was successfully formed with a 1:1 stoichiometry. The presence of cyclodextrin in the loading solution resulted in the improvement of drug loading onto resin.Conclusions: Enhancing drug loading onto ion-exchange resin via the formation of cyclodextrin inclusion complex is usable in the development of ion-exchange based drug delivery systems, which will beneficially reduce the use of harmful acidic or basic and organic chemicals.

Formulation and Optimization of Drug-Resin Complex Loaded Mucoadhesive Chitosan Beads of Repaglinide Using Factorial Design

<b> </b>Some ion exchange resins like Cholestyramine (Duolite AP-143), provide extended gastric retention and have the ability to coat the gastric mucosa uniformly. The use of such mucoadhesive ion exchange resins is another attractive approach in the development of targeted formulations for the GIT. In pesent work, a mucoadhesive gastroretentive system for Repaglinide was developed and optimized using Duolite AP-143 resin by RSM. Studies were carried out to develop and optimize oral mucoadhesive beads for Repaglinide using ion exchange resin and chitosan. Resinates prepared were studied for the effect of pH and drug resin ratio on drug loading. Resin and resinates were evaluated for mucoadhesive property using falling liquid film method. Resin and resinates showed sufficient mucoadhesion strength when compared with other mucoadhesive polymers and other ion exchange resins. Dissolution study of Repaglinide resinate showed that Duolite AP-143 was able to sustain the release of drug. The study suggests that the mucoadhesive beads of Repaglinide provide sustained release over 8 h and also shows sufficient mucoadhesive strength with rabbit gastric mucosa.

A simple and novel method for preparing the taste masking levofloxacin microsphere suspension

A taste masking levofloxacin resinate microsphere suspension was prepared. At first, levofloxacin-resinates were prepared by both bath and column methods in HCl solution (0.01 mol/L) before they were used as cores to prepare the suspension. The drug loading amount in the drug resinates made by bath method and column method was 33.2 ± 0.8 and 45.7 ± 0.6% (n = 6), respectively. The average diameter of the drug resinates was 120 μm. The scanning electron microscopy (SEM) results showed that there was no drug crystallization on the surface of the drug resinates. The in vitro drug release results showed that the drug resinates did not release levofloxacin in water, and the drug released faster with the increase of ion concentration in the dissolution mediums. The taste masking evaluation of the suspension was carried out among 6 volunteers; taste evaluation revealed that the suspension masked the bitter taste of the drug completely. Lastly, in vivo pharmacokinetics evaluation was carried out in beagle dogs. The in vivo pharmacokinetics test showed that the suspension and reference (levofloxacin tablets) had no significant differences for Cmax and AUC0-36h, but indicated a significant difference for Tmax. The Tmax decreased from 1.83 h (reference) to 1 h (test), indicating a faster release property in vivo. Key words: Levofloxacin, ion exchange resin, suspension, in vivo, taste masking.

Complexation using direct current: novel batch method for drug–resinate preparation

Pharmaceutically, resinates are used for the development of drug delivery technologies including targeted drug delivery, taste masking, dissolution improvement of drug and its stabilization. Laboratory methods used for the preparation of resinates involve the reaction between drug and ion exchange polymer by column or batch process. Present study investigated the effect of electric current (0.1–10 mA) on the complexation of drug, verapamil hydrochloride (model drug) with resin. Direct current (DC) (1 mA) applied during activation or complexation alone or both demonstrated significant increase in verapamil hydrochloride–resin complexation as compare to conventional methods. Moreover, further increase in intensity of current above 1 mA failed to increase the drug binding. This study suggests the use of electric current as a novel batch method for the preparation of drug–resinates.

Formulation and evaluation of taste masked mouth dissolving tablets of levocetirizine hydrochloride.

Aim of this research work was to develop mouth dissolving tablet that disintegrates rapidly in mouth by using tasteless complex of Levocetirizine and Tulsion-335. Effect of different parameters such as swelling time, resin activation, drug resin ratio as well as stirring time was optimized by taste and percentage drug loading. Formulated DRC (Drug Resin Complex) was characterized by infrared spectroscopy, thermal analysis and X-ray diffraction pattern. Tablets were formulated by wet granulation with PVP as binder, Sodium Starch Glycolate (SSG) and Crospovidone as super disintegrants. In these batches optimum hardness was achieved but disintegration time was found to be very high as ≥ 70 second, so further trials were planned by using different superdisintegrants such as Croscarmellose sodium, Sodium Starch Glycolate (SSG) as well as Crospovidone by wet granulation method. Tablets formulated with 7.5% crospovidone showed comparatively low disintegration time (25 sec), wetting time (20 sec) and friability (0.60 %) than the other batches. In present study we optimized the conditions required for maximum drug loading of Levocetirizine with Tulsion-335. Among different superdisintergants, crospovidone was found suitable with drug-resin complex to get the low disintegration time, wetting time and friability of tablets.

Preparation of modified release diltiazem HCl capsule by complexation with ion exchange resin

Background: Diltiazem HCl is a calcium channel blocker drug used in the treatment of angina pectoris and hypertension. Objective: To prepare a sustained release diltiazem HCl capsule by complexation with polystyrene sulfonate strong cation exchange resin (dowex®50wx4) as a complexing and retarding agent. Methods: The effect of stirring time and drug: resin ratio on diltiazem HCl loading on dowex®50wx4 was studied. Drug resin complexes were characterized by Fourier Transform Infrared (FT-IR) spectroscopy. The release of drug from the complexes was examined in pH 1.2 and pH 6.8 separately in comparison with pure drug and with commercially available sustained release products Tildia® 120mg capsule and BITildiem ® 120mg tablets Results and conclusion: Most efficient loading was obtained using 1:2 and 1:2.5 drug:resin ratio with stirring time of 60 and 30 minutes respectively. The resultant complexes only retard the release of diltiazem HCl when compared with pure drug while the sustained release product was obtained by coating the complex with carnauba wax and the retardation increased as a function of wax concentration. 20% of wax coated complex gave the release profile approximately similar to the marketed sustained release product of diltiazem HCl, Bi-Tildiem® (Sanofi-France) 120 mg tablets.

Formulation and development of taste masked fast-disintegrating tablets (FDTs) of Chlorpheniramine maleate using ion-exchange resins

Context: Masking of bitter taste of drug for better patient compliance.Objective: The objective of this research was to mask the bitter taste of Chlorpheniramine maleate using cation exchange resins.Materials and methods: Different cation exchange resins were used for taste masking. The drug resin complexes (DRC) were prepared by batch process. Complexes of ion-exchange resin and Chlorpheniramine maleate were prepared by taking drug: resin ratios 1:1, 1:2, 1: 3 and 1:4 (w/w). The optimum drug: resin ratio and the time required for maximum complexation was determined. The drug resinates were evaluated for the drug content, taste, drug release, FTIR, DSC and X-ray diffraction (PXRD).Results and discussion: The X-ray diffraction study confirmed the monomolecularity of entrapped drug in the resin beads. The taste evaluation depicted the successful taste masking of Chlorpheniramine maleate with DRCs. Fast disintegrating tablets (FDTs) were developed depending upon percent complexation, release study at salivary and gastric pH, taste evaluation; Chlorpheniramine maleate: Indion-234 complex of ratio 1:2 was used to develop and formulate FDTs. The drug release of 94.77% in 30 min was observed from FDTs.Conclusion: The Effective taste masking can be obtained from DRC that can be formulated as FDTs for better patient compliance.

ORAL CONTROLLED RELEASE METFORMIN HYDROCHLORIDE ION EXCHANGE RESINATE BEADS

Treating with ion exchange resin has chemically modified metformin hydrochloride to form an oral controlled release beads using ion-exchange resin sorption method. A strong cation exchange resin Amberlite IR 120 was utilized for the sorption of the drug and the drug resinates was evaluated for various physical and chemical parameters. The drug content and percentage drug release were determined spectrophotometrically at 233 nm. About 43% of drug was loaded in 4.5 h and in-vitro dissolution study showed 84% of drug release in 8 h. The drug-resinate complex was microencapsulated with a polymer Eudragit RS 100 to further retard the release characteristics. Further, the drug-resinate complex and microencapsulated drug resinate were suspended in a palatable aqueous suspension base and were evaluated for controlled release characteristic.