Drug-resin Complex Research Articles

Construction and in vitro/in vivo evaluation of menantine hydrochloride oral liquid sustained-release drug delivery system

Objective The purpose of the present study was to formulate a menantine hydrochloride (MH) sustained-release suspension. Methods Menantine hydrochloride drug resin complex (MH-DRC) was prepared with strong acid cation exchange resin as carrier using water bath method. The MH-DRC was characterized using scanning electron microscopy, X-ray diffraction and infrared spectroscopy. The MH-coated microcapsule (MH-CM) with optimized formulation was further dispersed in a suitable medium to obtain a sustained-release suspension. The rats were given both the MH sustained-release suspension and the commercial MH sustained-release capsule by intragastric administration. The plasma concentration-time curves and related pharmacokinetic parameters were also investigated using a non-atrioventricular model. Results MH and ion-exchange resin were ionically bonded. AmberliteIRP®69 had a higher affinity for MH at the initial concentration of 5 mg·mL−1 and a reaction temperature of 25.0 ± 0.5 °C. In vitro drug release profile showed that both the drug resin complex and the coated microcapsules had a certain level of sustained-release effect. The t1/2 of MH sustained-release suspension was extended from 68.44 h to 72.79 h with the peak blood concentration being decreased to 3.56 μg·mL−1 and the Tmax extended to 12 h compared with the commercial MH sustained-release capsule. The concentration-time curve of the self-made MH sustained-release suspension was flattened and the average relative bioavailability (Fr ) was 116.65% compared with the commercial MH sustained-release capsules. Conclusions The findings showed that the MH sustained-release suspension was successfully formulated with acceptable pharmacokinetic indices for effective treatment of Alzheimer’s disease.

Assessing Abuse-Deterrent formulations utilizing Ion-Exchange resin complexation processed via Twin-Screw granulation for improved safety and effectiveness

Opioid misuse is a public health crisis in the United States. In response, the FDA has approved drug products with abuse-deterrent features to reduce the risk of prescription opioid abuse. Abuse-deterrent formulations (ADFs) typically employ physical or chemical barriers or incorporate agonist–antagonist combinations as mechanisms to deter misuse. This study aims to assess the impact of abuse-deterrent properties, specifically ion-exchange resin complexation as a chemical barrier, on a model drug, promethazine hydrochloride (PMZ) tablets. Various formulations were developed through twin-screw wet granulation (TSWG) followed by twin-screw melt granulation (TSMG). In the TSWG process, the drug interacts with the resin through an exchange reaction, forming a drug-resin complex. Additionally, the study explored factors influencing the complex formation between the drug and resin, using the drug loading status as an indicator. DSC and ATR studies were carried out to confirm the formation of the drug-resin complex. Subsequently, hot melt granulation was employed to create a matrix tablet incorporating Kollidon® SR and Kollicoat® MAE 100P, thereby enabling sustained release properties. The drug-resin complex embedded in the matrix effectively deters abuse through methods like smoking, snorting, or parenteral injection, unless the drug can be extracted. In order to assess this, solvent extraction studies were conducted using an FDA-recommended solvents, determining the potential for abuse. Further investigations involved dissolution tests in change-over media, confirming the extended-release properties of the formulation. Results from dissolution studies comparing the ground and intact tablets provided positive evidence of the formulation's effectiveness in deterring abuse. Finally, alcohol-induced dose-dumping studies were conducted in compliance with FDA guidelines, concluding that the formulation successfully mitigates dose dumping in the presence of alcohol.

Taste Masking Cetirizine Hydrochloride using Ion-exchange Resins

Aim: The scope of the study is to determine the exact drug content present in the dry resinate and the utilization of ion-exchange resin in taste masking highly bitter cetirizine hydrochloride (CTZ). The Amberlite® IRP-69 cross-linked polystyrene was used. Objective: The objectives of this study are drug loading, drug–resin ratios, effect of particle size determination, and qualitative evaluation of taste masking ion-exchange resins. Background: The resinate (drug–resin complex) preparation process was completed by batch method in the ratio of 1:1, 1:2, and 1:3. The loaded drug amount in the resin was evaluated spectrophotometrically by measuring the remaining drug to be loaded in the solution at 278nm. Different sieve sizes of Amberlite® IRP-69 resins were employed to determine the effect of the particle size in drug loading and drug releasing profiles in simulated gastric fluid without enzymes. The X-ray diffractograms of cetirizine hydrochloride, Amberlite® IRP-69, and a mixture of cetirizine hydrochloride with resins (resinate) were obtained by using an X-ray diffractometer. Results: Resinates were developed by using single-batch and double-batch methods. Both of them are giving almost the same results of drug loading into ion-exchange resins. We selected 1:1 drug–resin ratio to see the effect of the particle size on the rate and extent of drug loading and drug releasing from the complex. In the 1:1 drug-to-resin ratio, almost 78% of the drug was involved in the complex after 24 hours; in the case of 2:1 and 3:1 ratios, only 49% and 25% of the drug were involved in the complex, respectively. Conclusion: Among many taste masking methods, the formation of resinates with an ion-exchange resin is simple and inexpensive. The present work reveals that the degree of bitterness of cetirizine hydrochloride is reduced to zero by strong cation-exchange resin. The present study deals on the scope of utilizing ion-exchange resins in taste masking cetirizine hydrochloride (CTZ), a highly bitter drug.

Preparation of Sustained Release Formulation of Verapamil Hydrochloride Using Ion Exchange Resins.

The purpose of this investigation was to formulate and evaluate the interaction between cation exchange resins and verapamil hydrochloride. The uptake studies were conducted using the rotating bottle apparatus. The Langmuir-like equation was applied to the experimental data and the maximum drug loading was determined from the Langmuir-like parameters. The drug-resin complexes were evaluated using XRD, SEM, and particle size analysis. Release studies were performed using USP dissolution apparatus 2. The resin with the lowest percentage of cross-linking had the highest uptake capacity. The percent increase in particle size due to complexation was found to be associated with drug loading; the highest drug loading had the highest increase in particle size. The X-ray diffraction patterns of the resins and the drug-resin complexes showed that they were both amorphous. The maximum drug release was approximately 40% when conventional dissolution testing was used. Results showed that sink conditions could not be maintained using conventional dissolution methods. Maximum drug release increased dramatically by increasing the volume of samples withdrawn and fresh dissolution medium added. Excellent correlation was obtained between sample volume and drug release rate with an R-value of 0.988. Particle diffusion-controlled model and film diffusion-controlled model were both applied to the experimental data. The results indicated that the rate-limiting step is the diffusion of the exchanging cations through the liquid film. The modified release formulation was prepared successfully and correlated very well with the USP monograph for verapamil hydrochloride extended release capsules.

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.

Formulation and in vitro Evaluation of Taste-Masked Orodispersible Tablets of Levocetirizine Dihydrochloride

The main aim was to formulate and evaluate and optimize taste- masked orodispersible tablets of Levocetirizine Dihydrochloride, a drug used in Allergic Rhinitis was prepared by direct compression method. The study involved different excipients which were used for the formulation and tested for their compatibility with Levocetirizine Dihydrochloride by the FT-IR studies. Based on the results of FT-IR studies, most of the excipients were found to be compatible with Levocetirizine which was used for the preparation of Levocetirizine oral disintegrating tablets. Levocetirizine Dihydrochloride is bitter in taste so the Tulsian-339 (ion exchange resin) was used to mask the taste to formulate an orodispersible dosage formulation using drug resin complex. Nine batches (F1-F9) of oro dispersible tablets of Levocetirizine Dihydrochloride were prepared by using super disintegrants like Sodium starch glycolate, Avicel PH102 and Low Hydroxy Propyl Cellulose in variable concentrations along with excipients for the development of optimized formulation. All formulations were subjected to evaluation studies of drug content, weight variation, water absorption ratio, wetting time, in vitro disintegration, dispersion time, hardness, friability and thickness uniformity. The tablets were disintegrated in vitro within 28-38 seconds, the complete drug was released from the tablets within 15 min. The results showed that Levocetirizine dihydrochloride was successfully formulated into an orodispersible dosage form.

Methods and Characteristics of Drug Extraction from Ion-Exchange-Resin-Mediated Preparations: Influences, Thermodynamics, and Kinetics.

Since the discovery of ion-exchange resins, they have been used in many fields, including pharmacy. Ion-exchange resin-mediated preparations can realize a series of functions, such as taste masking and regulating release. However, it is very difficult to extract the drug completely from the drug-resin complex because of the specific combination of the drug and resin. In this study, methylphenidate hydrochloride extended-release chewable tablets compounded by methylphenidate hydrochloride and ion-exchange resin were selected for a drug extraction study. The efficiency of drug extraction by dissociating with the addition of counterions was found to be higher than other physical extraction methods. Then, the factors affecting the dissociation process were studied to completely extract the drug from the methylphenidate hydrochloride extended-release chewable tablets. Furthermore, the thermodynamic and kinetic study of the dissociation process showed that the dissociation process obeys the second-order kinetic process, and it is nonspontaneous, entropy-decreasing, and endothermic. Meanwhile, the reaction rate was confirmed by the Boyd model, and the film diffusion and matrix diffusion were both shown to be rate-limiting steps. In conclusion, this study aims to provide technological and theoretical support for establishing a quality assessment and control system of ion-exchange resin-mediated preparations, promoting the applications of ion-exchange resins in the field of drug preparation.

FORMULATION, DEVELOPMENT AND IN VITRO EVALUATION OF TASTE MASKING MOUTH DISSOLVING TABLET OF LEVOCETIRIZINE DIHYDROCHLORIDE

Levocetirizine dihydrochloride is a selective, long acting peripheral H1receptor antagonist. 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 into an mouth dissolving tablet dosage form would provide fast relief. The Levocetirizine is bitter in taste so the Kyron T-114 (ion exchange resin) was used to mask the taste and to formulate an mouth dissolving tablet dosage form using drug resin complex. The tablets were evaluated for the drug content, weight variation, water absorption ratio, wetting time, in vitro disintegration, dispersion time, hardness, friability, thickness uniformity. The tablets disintegrated in vitro within 22 to 66 seconds complete drug were released from tablet within 10 minutes.

Formulation Optimization and Evaluation of Orally Disintegrating Tablets of Moxifloxacin

Oral administration of a pharmacologically active agent is the common and most preferred route among patients suffering from different types of illness. In the market, different type of oral dosage form is available among them tablet is the most favorite and demanded formulation. Further, the tablets, which are easy to use and swallow, are the ideal dosage form like orally disintegrating tablets (ODT’s). The main advantage of this type of formulation is that they can give easily to old aged and under-aged patients. In this research work, ODT’s formulation was manufactured, which get easily disintegrates and gives no bitter taste in the buccal cavity during administration. To achieve this task, moxifloxacin was complexed with suitable ion exchange resins (IER) like Kyron T314. In this course of action, multiple trials were performed using variable percentages or ratio of moxifloxacin and Kyron T 314. The resulting complex powder was characterized by different parameters like IR spectroscopy and differential scanning calorimetry (DSC). Along with the other excipients, drug resin complex (DRC) was used to manufacture the tablets. In this process, two super disintegrants viz. cross povidone and Ac di sol were used, and tablets were prepared by direct compression methodology. The finished product parameters of the tablet were estimated using the different available analytical methodologies. In this research work, it was concluded that the minimum time (19 seconds) for the wetting of tablets was observed when the quantity of crospovidone used was around 10% (MIT05). Additionally, this formulation gives maximum drug release (84.48%) after 120 minutes. Therefore, by using a suitable IER, taste-masked ODT’s of moxifloxacin can be prepared. This method is more efficient and effective in the development of such type of formulations.

Formulation Optimization and Evaluation of Taste Masked Oro-dispersible Tablet of Levocetrizine Dihydrochloride by Ion Exchange Resin

The aim of this study was to prepare ODT of taste masked levocetrizine dihydrochloride by using ion exchange resin. Levocetrizine Dihydrochloride is bitter in taste, Kyron T-134 a weak cationic exchange resin was used to mask the bitter taste of the drug. The ODTs were prepared by using drug-resin (DRC) complex using batch process. Compression of ODTs was done by using direct compression method with the technique of addition of superdisintegrants. Central composite design (CCD) was applied as an optimization technique. FTIR and DSC studies indicated drug and excipients were compatible with each other. The prepared orodispersible tablet blend and tablets were evaluated for various pre-compression and post-compression parameters. The Batch LH3 was given as optimized batch by central composite design. This optimized batch LH3 was passed all the pre-compression and post- compression parameters. The prepared ODTS showed successfully rapid onset of action with decrease in disintegration time 26 sec and %drug released was found to be 98.26%. It was concluded that levocetrizine dihydrochloride ODTs were prepared successfully by taste masking method using Kyron T-134 ion exchange resin and croscarmellose sodium as Superdisintegrant using CCD. AS per CDER guidelines, it shows DT within 5-30 sec.

NOVEL FORMULATION DESIGN AND IN-VITRO EVALUATION OF EXTENDED RELEASE PELLETS BY COMPLEXATION TECHNIQUE

This research was undertaken with an aim to formulate dextromethorphan hydrobromide as extended release micropellets. The Preformulation studies were carried out on drug Dextromethorphane Hydrobromide and it was shows that Drug has good flow property. Various ion exchange resins were screened for complexation with the drug and ratio of drug: resin was optimized along with manufacturing process for complexation. The Drug-Resin complex was further coated with suitable hydrophobic release rate retarding polymeric coatings using fluid bed processor. Optimization of % Ethyl Cellulose coat on drug-resin complex was carried out and 23.5% EC coat was selected for preparing final batch of micropellets of the drug Dextromethorphan hydrobromide.

Design and evaluate the mebendazole taste mask chewable tablets using ion exchange resin Kyron T-114

The aim of this research was to mask the bitter taste of Mebendazole using ion exchange resin and to formulate a taste masked chewable tablet. Kyron T-114 was used as a taste masking agent which was containing cross-linked polyacrylic backbone was used as taste masking agents. The drug resin complex was prepared by complexation of drug with resin using batch method. Maximum drug loading capacity of resins Kyron T-114 was calculated then Drug Resin Complexes were optimized by effect of drug resin ratio, Effect of stirring time. Effect of soaking time, effect of temperature and effect of pH on drug loading. Drug resin complex was evaluated for FTIR studies, drug release at salivary pH 6.8 and dissolution of drug resin complex at gastric pH. Taste masked chewable tablets of Mebendazole were prepared by direct compression method. Post compression evaluations used such as thickness, diameter, weight variation, hardness, disintegrating test, content uniformity test and in vitro dissolution test.

Formulation of sustained-release orodispersible film containing drug–resin complexes of donepezil hydrochloride

Formulation of sustained-release orodispersible film containing drug–resin complexes of donepezil hydrochloride

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 in vitro/in vivo evaluation of a clonidine hydrochloride drug–resin suspension as a sustained-release formulation

Objective The purpose of the present study was to prepare a clonidine hydrochloride (CH) sustained-release suspension. Methods The processes involved in the drug formulation included drug loading, impregnating, and suspension preparation. Clonidine hydrochloride drug–resin complexes (CH-DRC) were prepared using the bath method and the CH-DRC impregnated before the microencapsulation process. Based on the bottom spray fluidized bed coating method, the CH microencapsulated drug–resin complexes (CH-MC) were also prepared using Surelease® (the suspension of ethyl cellulose aqueous dispersion) as the coating material. The effects of coating (process/formulation) on the in vitro release of coating microcapsule were evaluated via single factor investigation and orthogonal design optimization. The CH-MC with optimized formulation was further dispersed in a suitable medium to obtain a sustained-release suspension. Rats were given commercial CH ordinary tablets and the CH sustained-release suspension via intragastric administration. The plasma concentration–time curve and related pharmacokinetic parameters were investigated using the non-compartment model. Results The T max of the CH sustained-release suspension was delayed from 2 h to 5 h compared with the CH ordinary tablets. Similarly, the C max was reduced from 32.138 µg·mL−1 to 18.150 µg·mL−1 with the concentration–time curve being more gentle compared with the commercially CH ordinary tablets. After oral administration, the relative bioavailability of CH sustained-release suspension (AUC0–24 of 137.703 µg·h·mL−1) to its CH ordinary tablets (AUC0–24 of 123.337 µg·h·mL−1) was 111.65%. Conclusions The findings showed that the CH sustained-release suspension for oral administration was successfully formulated.

Repaglinide and Metformin-Loaded Amberlite Resin-Based Floating Microspheres for the Effective Management of Type 2 Diabetes

Low bioavailability of anti-diabetic drugs results in the partial absorption of the drug as they are mainly absorbed from the stomach and the lower part of the GIT. Drug bioavailability of anti-diabetic drugs can be significantly increased by prolonging gastric retention time through gastro-retentive dosage form such as floating microspheres. The study was aimed to develop and characterize resin based floating microspheres of Repaglinide and Metformin for superior and prolonged maintenance of normoglycaemia in type-2 diabetes mellitus. Repaglinide and metformin were complexed with amberlite resin; later resin complexed drug was encapsulated in Ethylcellulose floating microspheres. Floating microspheres were characterized for morphology, particle size, IR spectroscopy, DSC, in vitro release and buoyancy studies. Further, floating microspheres were tested for in vivo blood glucose reduction potential in Streptozocin- induced diabetic mice. Floating microspheres had a spherical shape and slightly rough surface with the entrapment efficiency in a range of 49-78% for metformin and 52-73% for repaglinide. DSC studies revealed that no chemical interaction took place between polymer and drugs. Floating microspheres showed good buoyancy behavior (P<0.05) and prolonged drug release as compared to plain drug (P<0.05). The blood glucose lowering effect of floating microspheres on Streptozocin induced diabetic rats was significantly greater (P<0.05) and prolonged (˃12h) and normoglycaemia was maintained for 6hr. Floating microspheres containing drug resin complex were able to prolong drug release in an efficient way for a sustained period of time; as a result, profound therapeutic response was obtained.

A STATISTICAL APPROACH TO DEVELOPMENT OF TASTE MASKED EFFERVESCENT TABLETS OF SILDENAFIL CITRATE CONTAINING KYRON T134

Objective: The aim of present work was to mask the bitter taste of sildenafil citrate by preparing drug resin complex (DRC) and develop sildenafil citrate 100 mg effervescent tablets.&#x0D; Methods: Sildenafil citrate and kyron T134 complexes were prepared at different conditions and evaluated for taste and drug loading. Optimized DRC was use to formulate the dispersible tablet by direct compression technique. A 32 full factorial design was use to study the effect of effervescent agent (X1) and croscarmellose sodium (X2) on dispersion time (Y1) and wetting time (Y2). Factorial batches were also evaluated for thickness, hardness, content uniformity, friability, in vitro drug release and stability studies. Multiple linear regression analysis, ANOVA and graphical representation of the influence factor by 3D plots were performing by using sigma plot 11.0. A Check point batch was design according to the results of desirability value and evaluated for all the parameter&#x0D; Results: FT-IR study confirm that sildenafil citrate and kyron T134 were compatible with each other. Among the various DRC batch B29 was found with less bitter and give a more drug loading. Checkpoint batch showed no significance difference between predicted value and actual value for dispersion time and wetting time and it was found stable during stability study.&#x0D; Conclusion: Sildenafil citrate bitter tast was masked by kyron T134 and full factorial design result was indicate that independent variables have significant effect on dependent variables

Comparison of thermosensitive in situ gels and drug-resin complex for ocular drug delivery: In vitro drug release and in vivo tissue distribution.

Conventional ophthalmic eye drops are limited by their rapid elimination rate and short time of action. Ion exchange resin has been used to achieve sustained ocular drug delivery but the high selectivity of drug molecules restricts its broad application. In situ gel system seems to be a good strategy to address these problems but the influence of in situ gel type on the sustained release behavior and tissue distribution after ocular application is unclear. Therefore, in this study, using betaxolol hydrochloride as a model drug, poloxamer 407 and methylcellulose as the carriers, two thermosensitive in situ gel systems were prepared and characterized. Influence of formulation composition type and concentration on in vitro drug release was studied. Tissue distribution after ocular delivery of two different thermosensitive in situ gels was studied and compared with commercial BH eye drop (Betoptic S®). In vitro studies demonstrated that addition of 4% HPMC 606W in 15% P407 solution and 5% PEG4000 in 2% MC solution obtained gels with appropriate gelation temperature and similar sustained drug release rate. In vivo tissue distribution study indicated that they presented similar drug concentration in cornea, iris-ciliary and aqueous humor irrespective of gel type, with higher drug concentration achieved after 4h compared to the commercial resin suspension eye drops. The AUC and MRT of the two in situ gel eye drops were 2 times higher than that of the commercial resin suspension eye drops in cornea. In conclusion, the two thermosensitive in situ gels have prolonged drug release after ocular drug delivery compared with ion exchange resin eye drops, implying their potential applications in clinic with broad drug adoptability.

Development of medicated chewing gum of taste masked levocetirizine dihydrochloride using different gum bases: in vitro and in vivo evaluation

Objective: The aim of this study was to develop medicated chewing gum (MCG) formulation for taste-masked levocetirizine dihydrochloride (LCZ) that can provide fast drug release into the salivary fluid.Methods: Taste-masked LCZ was first prepared by two methods: cyclodextrin complexation using Kleptose or Captisol and formation of drug resin complex using Kyron T-154 or Kyron T-314 to overcome poor LCZ palatability. MCGs were then prepared using the taste-masked drug, gum base (Artica-T, Chicle, or Health In Gum (HIG), plasticizer (glycerol or soy lecithin at 6 or 8% of the final gum weight). The developed MCGs were evaluated for physical properties, content uniformity, and drug release. Best release MCGs were evaluated thermally to investigate the plasticizer effectiveness and for ex vivo chew out study to confirm adequate drug release. Drug bioavailability was determined for selected formula compared to commercial tablets.Results: Based on taste-masking efficiency, drug/Kleptose complex (1:3 molar ratio) was chosen for incorporation into chewing gums. Physical properties and drug release showed that gum base type, plasticizer type, and level affected not only physical properties but also drug release from MCGs. Thermal study showed decreased glass transition temperature (Tg) with increased plasticizer level. Chew out study confirmed almost complete drug release after a few minutes of chewing. Pharmacokinetic results showed shorter tmax (0.585 vs. 1.375 h) and higher Cmax (0.113 vs. 0.0765 μg/mL) for MCGs than conventional tablets.Conclusion: Results provided evidence that MCGs could be a better alternative to conventional tablet formulations with improved bioavailability and enhanced palatability.

DESIGN, OPTIMIZATION, AND STATISTICAL EVALUATION OF ORAL RECONSTITUTED SUSPENSION OF CLARITHROMYCIN USING ION-EXCHANGE RESINS

Objectives: The objective of the present study is taste masking of bitter clarithromycin using Indion 204, Indion 234, and Tulsion 335 as ion-exchange resins, which forms insoluble complexes, inhibiting the drug release in saliva as ion-exchange resins are cross-linked polymers, water-insoluble that contains salt-forming groups in repeating positions on the polymer chain. Drugs that are bitter and cationic get adsorbed onto weak cationic exchange resins of carboxylic acid functionality such as Indion 204, Indion 234, and Tulsion 335 to form non-bitter complexes.&#x0D; Methods: The drug-resin complex loading process was optimized for the resin content, activation, swelling time, stirring time, influence of pH, and temperature for maximum drug loading and the formed complex was evaluated by differential scanning calorimetry (DSC) to confirm complex formation. The drug-resin complex was also characterized by their micromeritic and rheological properties. These complexes were used to prepare oral reconstituted suspensions and the taste was evaluated. The formulation was evaluated for various parameters such as sedimentation volume, pH, redispersibility, viscosity, drug content, and in vitro drug release.&#x0D; Results: Acid-activated resins comprising Indion 204, Indion 234, and Tulsion 335 with the drug:resin ratio of 1:2, stirred in a solution of pH 7–8 at 70° for 6 h had a maximum drug loading and masked the bitter taste of clarithromycin. DSC of the drug-resin complex (DRC) revealed that there was interaction leading to complex formation. The drug-resin complex was formulated into suspension formulations (S1-S9) and evaluated. Various parameters were found to be within permissible limits. Formulations S3, S6, and S9 containing 1:2 ratios of the drug-resin complex of Indion 204, Indion 234, and Tulsion 335 revealed maximum taste masking. This was further confirmed by treatment of taste evaluation scores obtained from the volunteers by ANOVA, Dunnett’s multiple comparison test, and Tukey’s multiple comparison test. All the three optimized formulations had a significant difference of p&lt;0.001 when compared to control S10. S6 formulation was widely accepted.&#x0D; Conclusion: Ion-exchange complexation could efficiently mask the bitter taste of clarithromycin and achieve palatable taste suitable for pediatric use.