Development and Optimization of Andrographis paniculata Extract-Loaded Self-Microemulsifying Drug Delivery System Using Experimental Design Model.

The objectives of this study were to develop an optimized formulation for an Andrographis paniculata extract (AGPE)-loaded self-microemulsifying drug delivery system (SMEDDS) using an experimental design and evaluate the characteristics of the developed SMEDDS. The solubility of andrographolide (AGP) in various solvents was investigated. The pseudo-ternary phase was constructed to provide an optimal range for each component to form microemulsions (MEs). The formulation was optimized using an I-optimal design mixture type, where the physical stability, droplet size, polydispersity index, and zeta potential were examined. Soft capsules of the optimized AGPE-loaded SMEDDS were manufactured. The dissolution and ex vivo membrane permeation were studied. Oleic acid, Tween® 80, and PEG 400 were the best solubilizers for AGP. The promising surfactant to co-surfactant ratio to generate ME was 3:1. The optimized SMEDDS contained 68.998% Tween® 80, with 13.257% oleic acid and 17.745% PEG 400. The assayed content of AGP, uniformity of dosage unit, and stability complied with the expected specifications. The dissolution and membrane permeability of AGPE-loaded SMEDDS was significantly improved from the A. paniculata extract (p < 0.05). All in all, the developed optimized AGPE-loaded SMEDDS was proven to contain optimal composition and AGP content where a stable ME could spontaneously be formed with enhanced delivery efficacy.

Design and Optimization of 3D-Printed Gastroretentive Floating Devices by Central Composite Design.

This study aimed to optimize the size of capsule-shaped 3D-printed devices (CPD) using an experimental design by the response surface methodology to provide a gastroretentive drug delivery system (GRDDS) with optimal floating time. The CPD was fabricated using a fused deposition modeling (FDM) 3D printer. The central composite design was employed for the optimization of the devices. The morphology of the CPD was observed using a digital microscope and scanning electron microscope (SEM). The in vitro floating time and drug release were evaluated using a USP dissolution apparatus II. Appropriate total floating time (TFT) of the devices (more than 3 h) was obtained with the device's body, cap, and bottom thickness of 1.2, 1.8, and 2.9 mm, respectively. The release kinetics of the drug from the devices fitted well with zero-order kinetics. In conclusion, the optimization of CPD for GRDDS using the experimental design provided the devices with desirable floating time and ideal drug release characteristics.

Three-dimensional (3D)-printed devices composed of hydrophilic cap and hydrophobic body for improving buoyancy and gastric retention of domperidone tablets.

The aim of this study was to produce capsule-shaped floating devices (CFD) using a fused deposition modeling (FDM) three-dimensional (3D) printer, for controlling the release and gastric retention of domperidone (DOM) tablets (Motilium-MⓇ). In order to enhance the buoyancy of the devices, a hollow cap with different wall thicknesses (1.2-1.5 mm) was printed with a hydrophilic (polyvinyl alcohol, PVA) filament. The body of the device was made from a hydrophobic (polylactic acid, PLA) filament. Bodies with aperture sizes (1-2 mm) were produced to investigate how this would affect drug release. Morphology, weight variation, ex vivo and in vivo floating time and drug release characteristics were examined. The results revealed that increasing the cap thickness of the devices (1.2 to 1.3 mm) increased the total floating time (TFT). The maximum TFT (10 h) with floating lag time (FLT) < 5 s was observed from Motilium-MⓇ incorporated CFD3-5 (cap with 1.3-mm wall thickness). Decreasing the size of the holes on the devices led to the sustained release of DOM. The CFD5 (cap with 1.3-mm cap thickness and 1.5-mm hole width) delivered approximately 98% release in 10 h, and the release kinetics fit well with the zero-order kinetics (R2 > 0.95). In vivo floating studies in rabbits showed that the floating time of CFD5 was more than 10 h. These results demonstrated that the CFD was successfully designed to provide gastro-retentive drug delivery with the capacity to float and provide sustained drug release.

Design and characterisation of electrospun shellac-polyvinylpyrrolidone blended micro/nanofibres loaded with monolaurin for application in wound healing.

Due to their ultrafine network structures, electrospun nanofibres have been potentially used for wound application. In order to develop a desired wound dressing material, shellac (SHL) was blended with polyvinyl pyrrolidone (PVP). Monolaurin (ML), which is a natural antimicrobial lipid, was incorporated into the SHL-PVP blended fibres to prevent delayed wound healing resulting from microbial infection. A full factorial design with three replicated centre points was employed in order to determine the main and interaction effects of various factors including SHL ratio in SHL-PVP blended solution, ML content and applied voltage on the multiple responses such as morphology, surface wettability, absorbency and mechanical properties. According to the results, an increase in the PVP content could lead to a significant increase in tensile strength and elongation. In addition, the presence of PVP contributed to an improvement in the drug loading capacity and dissolution rate. The fabricated fibres loaded with ML exhibited an excellent activity against Staphylococcus aureus and Candida albicans, and also provided an enhanced ability in the cell adhesion. Therefore, SHL-PVP blended fibres loaded with ML might be effectively used for application in wound healing.

Development of Microemulsions and Microemulgels for Enhancing Transdermal Delivery of Kaempferia parviflora Extract.

The purpose of this research was to develop microemulsions (ME) and microemulgels (MG) for enhancing transdermal delivery of Kaempferia parviflora (KP) extract. The methoxyflavones were used as markers. Various formulations of ME and MG containing 10% w/v KP extract were prepared, and the in vitro skin permeation and deposition were investigated. The potential ME system containing oleic acid (5% w/v), Tween 20 (20% w/v), PG (40% w/v), and water (35% w/v) was successfully formulated. ME with 10% w/v limonene (ME-L10%) showed higher methoxyflavones flux than ME-L5%, ME-L1%, ME without limonene, and KP extract in water, respectively. ME-L10% was selected for adding a gelling agent to form microemulgels (MG-L10%). However, the high viscosity of the gel formulation might control the diffusion of the compound from gel layer into the skin. Therefore, the liquid formulation provided potential ME droplets to deliver KP extract through the skin. Limonene also plays an effective role on the skin permeation, in which the histological image of the skin treated with ME-L10% exhibited larger space of each flattened keratinocyte layer in the stratum corneum compared to the skin treated with KP extract in water. Moreover, ME-L10% showed good stability. Therefore, ME-L10% was a potential formulation for improving transdermal delivery of KP extract.

Fabrication and characterization of spearmint oil loaded nanoemulsions as cytotoxic agents against oral cancer cell.

Spearmint oil (SMO), a commonly used essential oil for oral care products, possesses various interesting functions, especially for anticancer property. However, the application of SMO for cancer treatment is limited due to water insoluble. In the present study, nanoemulsions, which have been widely accepted as dosage forms for poorly water-soluble drugs, were selected as candidate carriers for SMO to inhibit oral cancer cell. The nanoemulsions were fabricated using phase inversion temperature method. The factors affecting formation and properties of nanoemulsions including type and amount of surfactants, oil loading and ratio of SMO to virgin coconut oil (VCO) were investigated. Among the surfactants used, the nanoemulsions containing polyoxyethylene castor oil derivatives (Kolliphor®EL; PCO35, Cremophor®RH40; PCO40, Eumulgin®CO60; PCO60) and polyoxyethylene sorbitan fatty acid esters (PSF80) showed 100% creaming after temperature cycling test indicating excellent physical stability while those containing PCO40 demonstrated more transparency and better physical stability. With an increasing amount of PCO40, the droplet size tended to decrease and was in the nano-size range (<1000 nm) after increasing to more than 5% (w/w). SMO-VCO loading also influenced on the droplet size. At 5% (w/w) PCO40, the maximum SMO-VCO loading of 25% (w/w) to attain nanoemulsions was observed. Moreover, the composition of oils had an impact on size of emulsions. The transparent nanoemulsions were only prepared in the range of SMO-VCO from 40:60 to 80:20, suggesting the optimum ratio of SMO to surfactant and the composition of oils were the critical factors for formation of nanoemulsions. NMR study disclosed that the interaction between PCO40 with both VCO and SMO should be a possible stabilization mechanism. Furthermore, the SMO-VCO nanoemulsions exhibited significant cytotoxic effect against oral carcinoma (KON) cell line using MTT assay. The finding, therefore, revealed the good feasibility of SMO-VCO nanoemulsions as novel carriers for treating of oral cancer.

Cyclodextrin-based oral dissolving films formulation of taste-masked meloxicam.

This work deals with fast-dissolving drug delivery systems of meloxicam (MX) derived from electrospun polyvinylpyrrolidone (PVP)/2-hydroxypropyl-ß-cyclodextrin (HPßCD) nanofiber mats. Electrospinning of solutions with different solvent systems [dimethylformamide (DMF) and ethyl alcohol (EtOH)] was performed. Prepared films were evaluated for morphology, physical, and mechanical properties. MX content, dissolving time, MX release, and cytotoxicity of films were investigated. In vivo studies were also performed in healthy human volunteers. The results showed that MX/HPßCD complexes improved the solubility of MX. PVP also increased MX solubility and the stability of MX/HPßCD complexes. Films were successfully prepared by two solvent systems with fiber in the nanometer range. MX was well incorporated into the films (100% efficiency). The X-ray patterns and DSC experiment indicated an amorphous form of MX. A fast disintegration time and burst release of MX was obtained from EtOH system. Cytotoxicity testing of the films produced by EtOH system proved safer than the DMF system. In vivo studies revealed that films rapidly dissolved in the mouth and had a less bitter taste than MX. These results suggest that electospun films from EtOH system may be a good candidate for fast-dissolving drug delivery systems to increase palatability of dosage forms.

Development and evaluation of N-naphthyl-N,O-succinyl chitosan micelles containing clotrimazole for oral candidiasis treatment.

Clotrimazole (CZ)-loaded N-naphthyl-N,O-succinyl chitosan (NSCS) micelles have been developed as an alternative for oral candidiasis treatment. NSCS was synthesized by reductive N-amination and N,O-succinylation. CZ was incorporated into the micelles using various methods, including the dropping method, the dialysis method, and the O/W emulsion method. The size and morphology of the CZ-loaded micelles were characterized using dynamic light scattering measurements (DLS) and a transmission electron microscope (TEM), respectively. The drug entrapment efficiency, loading capacity, release characteristics, and antifungal activity against Candida albicans were also evaluated. The CZ-loaded micelles prepared using different methods differed in the size of micelles. The micelles ranged in size from 120 nm to 173 nm. The micelles prepared via the O/W emulsion method offered the highest percentage entrapment efficiency and loading capacity. The CZ released from the CZ-loaded micelles at much faster rate compared to CZ powder. The CZ-loaded NSCS micelles can significantly hinder the growth of Candida cells after contact. These CZ-loaded NSCS micelles offer great antifungal activity and might be further developed to be a promising candidate for oral candidiasis treatment.

Design of porous Eudragit® L beads for floating drug delivery by wax removal technique.

The aim of this study was to design porous matrix beads for floating drug delivery using enteric polymer, Eudragit® L and various amounts of waxes (0, 0.1, 0.5, 1, 2 and 3% w/w). In this study, wax containing cetyl alcohol and white petrolatum was utilized to produce pores using a wax removal technique. To prepare the beads, Eudragit® L, metronidazole and wax were dissolved in acetone and then extruded into dichloromethane. The effect of the amount of wax on the floating and drug release behavior of the Eudragit® L beads was determined. After the extruded product was immersed in dichloromethane, wax dissolved out from the formed beads, resulting in a porous structure. The prepared beads could float in simulated gastric fluid for more than 10 hours. Different amounts of wax had an effect on the drug release. We found that when the percentage of wax increased, the drug release was higher while the beads remained floating. The results suggest that Eudragit® L beads could be used as a carrier for an intragastric floating drug delivery system.

pH-Responsive polymeric micelles based on amphiphilic chitosan derivatives: Effect of hydrophobic cores on oral meloxicam delivery.

The amphiphilic chitosan derivatives, N-naphthyl-N,O-succinyl chitosan (NSCS), N-octyl-N-O-succinyl chitosan (OSCS) and N-benzyl-N,O-succinyl chitosan (BSCS), were synthesized. Meloxicam (MX) was loaded into polymeric micelles (PMs), and the effects of hydrophobic moieties of the inner core segment on the loading efficiency, stability of MX-loaded PMs, cytotoxicity, drug release, and porcine small intestine permeation were investigated. Among the hydrophobic cores, the N-octyl moiety revealed the highest MX loading efficiency and most stable MX-loaded PMs compared to the other hydrophobic cores. All PMs were spherically shaped (size 213-282 nm) and had low toxicity against Caco-2 cells. The release of MX from PMs was found to be dependent on both hydrophobic cores and hydrophilic shells. In acidic medium at 0-2h, low cumulative MX release was obtained in the MX-loaded OSCS PMs compared to MX-loaded NSCS PMs and MX-loaded BSCS PMs as well as MX free drug. However, when the pH was increased to 6.8, the MX release significantly increased in all MX-loaded PMs. Furthermore, the intestinal permeation rates of MX from all MX-loaded PMs were not significantly different. These results suggest that MX was successfully incorporated into the PMs at high efficiency and good stability by optimizing the hydrophobic moieties of the inner core segments.

Fast releasing oral electrospun PVP/CD nanofiber mats of taste-masked meloxicam.

Fast release and taste masking of meloxicam (MX)-loaded polyvinylpyrrolidone (PVP)/cyclodextrin (CD) nanofiber mats were developed using an electrospinning process. CDs were blended to improve the stability of the mats. The morphology and diameter of the mats were determined using scanning electron microscopy (SEM); physical and mechanical properties were also studied. The MX content, disintegration time, MX release and cytotoxicity of the mats were investigated. In vivo studies were also performed in healthy human volunteers. The results indicated that the mats were successfully prepared with fiber in the nanometer range. MX was well incorporated into the mats, with an amorphous form. The mats showed suitable tensile strength. CDs improved the physical stability by their cage-like supramolecular structure to protect from humidity and moisture, and create bead free nanofiber mats. The nanofiber mats with CDs were physically stable without any hygroscopicity and fusion. A fast disintegration and release of MX was achieved. Moreover, this mat released MX faster than the MX powder and commercial tablets. The cytotoxicity test revealed that mats were safe for a 5-min incubation. The disintegration studies indicated that in vivo disintegration agreed with the in vitro studies; the mat rapidly disintegrated in the mouth. The less bitter of MX was occurred in the mats that incorporated CD, menthol and aspartame. In addition, this mat was physical stable for 6 months. The results suggest that these mats may be a good candidate for fast dissolving drug delivery systems of bitter drugs to increase the palatability of dosage forms.

Fabrication and In Vitro/In Vivo Performance of Mucoadhesive Electrospun Nanofiber Mats Containing α-Mangostin.

This study aimed to fabricate mucoadhesive electrospun nanofiber mats containing α-mangostin for the maintenance of oral hygiene and reduction of the bacterial growth that causes dental caries. Synthesized thiolated chitosan (CS-SH) blended with polyvinyl alcohol (PVA) was selected as the mucoadhesive polymer. α-Mangostin was incorporated into the CS-SH/PVA solution and electrospun to obtain nanofiber mats. Scanning electron microscopy, differential scanning calorimetry, X-ray diffraction, and tensile strength testing were used to characterize the mats. The swelling degree and mucoadhesion were also determined. The nanofiber mats were further evaluated regarding their α-mangostin content, in vitro α-mangostin release, antibacterial activity, cytotoxicity, in vivo performance, and stability. The results indicated that the mats were in the nanometer range. The α-mangostin was well incorporated into the mats, with an amorphous form. The mats showed suitable tensile strength, swelling, and mucoadhesive properties. The loading capacity increased when the initial amount of α-mangostin was increased. Rapid release of α-mangostin from the mats was achieved. Additionally, a fast bacterial killing rate occurred at the lowest concentration of nanofiber mats when α-mangostin was added to the mats. The mats were less cytotoxic after use for 72 h. Moreover, in vivo testing indicated that the mats could reduce the number of oral bacteria, with a good mouth feel. The mats maintained the amount of α-mangostin for 6 months. The results suggest that α-mangostin-loaded mucoadhesive electrospun nanofiber mats may be a promising material for oral care and the prevention of dental caries.

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

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

Formulation and evaluation of meloxicam oral disintegrating tablet with dissolution enhanced by combination of cyclodextrin and ion exchange resins.

CONTEXT: The bitter taste of drug is masked by the exchange of ionized drugs with counter ions of ion exchange resin, forming "resinate". Cyclodextrin reduces the unpleasant taste and enhances the drug solubility by encapsulating drug molecules into its central cavity. OBJECTIVE: Oral disintegrating tablets (ODTs) using the combination of ion exchange resin and cyclodextrin was developed, to mask the bitter taste and enhance drug dissolution. METHODS: Meloxicam (MX) was selected as a model drug. Formulations containing various forms of MX (free drug, MX-loaded resin or resinate, complexes of MX and 2-hydroxypropyl-ß-cyclodextrin (HPßCD) or MX/HPßCD complexes, and a mixture of resinate and MX/HPßCD complexes) were made by direct compression. The ODTs were evaluated for weight variation, thickness, diameter, hardness, friability, disintegration time, wetting time, MX content, MX release, degree of bitter taste and stability. RESULTS AND DISCUSSION: The tablet hardness was ∼3 kg/in(2), and the friability was <1%. Tablets formulated with resinate and the mixture of resinate and MX/HPßCD complexes disintegrated rapidly within 60 s, which is the acceptable limit for ODTs. These results were corresponded to the in vivo disintegration and wetting times. However, only tablets containing the mixture of resinate and MX/HPßCD complexes provided complete MX dissolution and successfully masked the bitter taste. In addition, this tablet was stable at least 6 months. CONCLUSIONS: The combination of ion exchange resin and cyclodextrin could be used in ODTs to mask the bitter taste and enhance the dissolution of drugs that are weakly soluble in water.

Meloxicam taste-masked oral disintegrating tablet with dissolution enhanced by ion exchange resins and cyclodextrin.

The purpose of this study was to develop taste-masked oral disintegrating tablets (ODTs) using the combination of ion exchange resin and cyclodextrin, to mask the bitter taste and enhance drug dissolution. Meloxicam (MX) was selected as a model drug with poor water solubility and a bitter taste. Formulations containing various forms of MX (free drug, MX-loaded resin or resinate, complexes of MX and 2-hydroxypropyl-ß-cyclodextrin (HPßCD) or MX/HPßCD complexes, and a mixture of resinate and MX/HPßCD complexes) were made and tablets were prepared by direct compression. The ODTs were evaluated for weight variation, thickness, diameter, hardness, friability, disintegration time, wetting time, MX content, MX release, degree of bitter taste, and stability. The results showed that thickness, diameter, weight, and friability did not differ significantly for all of these formulations. The tablet hardness was approximately 3 kg/in.(2), and the friability was less than 1%. Tablets formulated with resinate and the mixture of resinate and MX/HPßCD complexes disintegrated rapidly within 60 s, which is the acceptable limit for ODTs. These results corresponded to the in vivo disintegration and wetting times. However, only tablets containing the mixture of resinate and MX/HPßCD complexes provided complete MX dissolution and successfully masked the bitter taste of MX. In addition, this tablet was stable at least 6 months. The results from this study suggest that the appropriate combination of ion exchange resin and cyclodextrin could be used in ODTs to mask the bitter taste of drug and enhance the dissolution of drugs that are weakly soluble in water.

Development and characterization of propranolol selective molecular imprinted polymer composite electrospun nanofiber membrane.

Propranolol (PPL) imprinted microspheres (MIP) were successfully prepared via oil/water polymerization using a methyl methacrylate (MMA) monomer, PLL template, and divinylbenzene (DVB) cross-linker and favorably incorporated in a Eudragit-RS100 nanofiber membrane. A non-PPL imprinted polymer (NIP), without a template, was used as a control. The morphology and particle size of the beads were investigated using scanning electron microscopy. The results revealed that both MIP and NIP had a spherical shape with a micron size of approximately 50-100 µm depending on the amounts of DVB and PPL used. NIP2 (MMA/DVB, 75:2.5) and MIP8 (PPL/MMA/DVB, 0.8:75:2.5) were selected for reloading of PPL, and the result indicated that increasing the ratio of PPL to polymer beads resulted in increase PPL reloading (>80%). A total of 10-50% NIP2 or MIP8 was incorporated into a 40% (w/v) Eudragit-RS100 fiber membrane using an electrospinning technique. PPL could be bound to the 50% MIP8 composite fiber membrane with a higher extent and at a higher rate than the control (NIP2). Furthermore, the MIP8 composite fiber membrane showed higher selectivity to PPL than the other ß-blockers (atenolol, metoprolol, and timolol). Thus, the MIP8 composite fiber membrane can be further developed for various applications in pharmaceutical and other affinity separation fields.

Fabrication and evaluation of cationic exchange nanofibers for controlled drug delivery systems.

The number of ion exchange fibers in development has increased over the last several years. However, few studies have reported the use ion-exchange fibers in drug delivery system. In this study polystyrene nanofiber ion exchangers (PSNIE) were fabricated by electrospinning techniques, crosslinking and sulfonation. The degree of crosslinking and the ion exchange capacity (IEC) were determined. The morphology and diameter of the nanofiber mats were analyzed using scanning electron microscopy (SEM). Five cationic model drugs (dextromethorphan, chlorpheniramine, diphenhydramine, propranolol and salbutamol) were loaded into PSNIE. The loading capacity, release and release kinetics of the exchangers were investigated. PSNIE were successfully prepared by electrospinning and were allowed to crosslink for 10 min, resulting in a maximum IEC of 2.86±0.1 meq/g dry PSNIE. The diameter of the fibers after sulfonation was 464±35 nm. Dextromethorphan provided the highest loading in PSNIE while diphenhydramine gave the highest percentage release in both simulated gastric and intestinal fluid (SGF and SIF). The release kinetics of all drugs in SGF and SIF provided the best fit with the particle diffusion model. Our results showed that the development of a PSNIE-based drug delivery system was successful, and PSNIE were able to control drug release.

Neomycin-loaded poly(styrene sulfonic acid-co-maleic acid) (PSSA-MA)/polyvinyl alcohol (PVA) ion exchange nanofibers for wound dressing materials.

In this study, poly(styrene sulfonic acid-co-maleic acid) (PSSA-MA) blended with polyvinyl alcohol (PVA) was electrospun and then subjected to thermal crosslinking to produce PSSA-MA/PVA ion exchange nanofiber mats. The cationic drug neomycin (0.001, 0.01, and 0.1%, w/v) was loaded onto the cationic exchange fibers. The amount of neomycin loaded and released and the cytotoxicity of the fiber mats were analyzed. In vivo wound healing tests were also performed in Wistar rats. The results indicated that the diameters of the fibers were on the nanoscale (250 ± 21 nm). The ion exchange capacity (IEC) value and the percentage of water uptake were 2.19 ± 0.1 mequiv./g-dry fibers and 268 ± 15%, respectively. The loading capacity was increased upon increasing the neomycin concentration. An initial concentration of 0.1% (w/v) neomycin (F3) showed the highest loading capacity (65.7 mg/g-dry fibers). The neomycin-loaded nanofiber mats demonstrated satisfactory antibacterial activity against both Gram-positive and Gram-negative bacteria, and an in vivo wound healing test revealed that these mats performed better than gauze and blank nanofiber mats in decreasing acute wound size during the first week after tissue damage. In conclusion, the antibacterial neomycin-loaded PSSA-MA/PVA cationic exchange nanofiber mats have the potential for use as wound dressing materials.

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: ß-Cyclodextrin (ß-CD) and hydroxypropyl ß-cyclodextrin (HP-ß-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.

Preparation and evaluation of taste-masked dextromethorphan oral disintegrating tablet.

This study was aimed at preparing and evaluating oral disintegrating tablets (ODTs) using a strongly cationic resin, Amberlite(®) IRP-69, to mask the bitter taste of a delivered drug, i..e. dextromethorphan hydrobromide. The drug was loaded into the resin (referred to as resinate) or physically mixed with the resin (referred to as physical mixture), and was then incorporated into ODTs by direct compression. A variety of formulae was developed to acquire the optimal formulations of taste-masked ODTs that had acceptable hardness and mouth feel (grittiness). The optimized ODTs were further evaluated for thickness, diameter, weight, friability, disintegration time, wetting time, wetting rate, drug content, drug release and degree of bitter taste, respectively. The thickness, diameter, weight and friability of the tablet with resinate were slightly higher than those with physical mixture. The tablet with resinate had a longer disintegration time, corresponding with its slower wetting time and rate. Both tablets with resinate and physical mixture provided a sustained pattern of drug release. However, only tablets with resinate successfully masked the bitter taste of the drug. In conclusion, the combination of drug and ion exchange resin as resinate could increase the palatability and acceptability of ODTs containing bitter drugs.