In situ ophthalmic gel of ciprofloxacin hydrochloride for once a day sustained delivery

This article focuses on preparation and evaluation of a once a day ophthalmic delivery system for ciprofloxacin hydrochloride based on the concept of pH-triggered in situ gelation. The in situ gelling system involves the use of polyacrylic acid (Carbopol® 980NF) as a phase transition polymer, hydroxypropyl methylcellulose (Methocel® K100LV) as a release retardant, and ion exchange resin as a complexing agent. Ciprofloxacin hydrochloride was complexed with ion exchange resin to avoid incompatibility between drug and polyacrylic acid. The developed formulation was stable, and nonirritant to rabbit eyes and in vitro drug release was found to be around 98% over a period of 24 hours.     

In Situ Ophthalmic Gel of Ciprofloxacin Hydrochloride for Once a Day Sustained Delivery

This article focuses on preparation and evaluation of a once a day ophthalmic delivery system for ciprofloxacin hydrochloride based on the concept of pH-triggered in situ gelation. The in situ gelling system involves the use of polyacrylic acid (Carbopol® 980NF) as a phase transition polymer, hydroxypropyl methylcellulose (Methocel® K100LV) as a release retardant, and ion exchange resin as a complexing agent. Ciprofloxacin hydrochloride was complexed with ion exchange resin to avoid incompatibility between drug and polyacrylic acid. The developed formulation was stable, and nonirritant to rabbit eyes and in vitro drug release was found to be around 98% over a period of 24 hours.     

In Vitro Adsorption-Desorption of Papaverine Hydrochloride by Montmorillonite

Abstract

In an attempt to obtain the basic data necessary in research into the possible use of papaverine in sustained action formulas in the form of complexes with Montmorillonite, the “in vitro” adsorption and desorption of the drug as a function of different factor was studied.

The study of the interaction and adsorption mechanisms was carried out by adsorption isotherms, X-ray diffraction and I.R. spectroscopy.

The adsorption of papaverine by Montmorillonite increases with the rise in pH of the solution, within the pH range studied (2-4) in agreement with the solubility of the compound. According to the isotherms, adsorption increases with the concentration of the solution up to 79.16 mEq/100 g (very close to the exchange capacity of the clay). The data fulfill Langmuir's equation, implying a chemical adsorption mechanism.

The results of the X-ray diffraction and I.R. spectroscopy studies confirm the intercalation of the organic cation into the interlayer space of montmorillonite, forming a complex of defined spacing (17.66 Å (DL = 8.06 Å)). The studies revealed that cation exchange is the mechanism responsible for this interaction.

The “in vitro” desorption studies showed that the amount of papaverine desorbed from the complex depends on the pH of the solution, on its ionic strength, on the presence of free drug and on the elimination rate of the desorbed complex; in all cases, desorption was seen to be very low.

In general, release of the drug follows a single first order kinetic process with a rapid initial desorption of the drug.     

Drug-Delivery by Ion-Exchange: Part IIII: Interaction of Ester Pro-Drugs of Propranolol with Cationic Exchange Resins

Abstract

The interaction of a series of O-n-acyl propranolol prodrugs with strong cation exchange resins is reported and various variables which control loading and release profiles have been investigated. pH has little practical effect on the loading efficiency under the conditions used but standardisation of experimental details for the measurement of in vitro liberation profiles must be undertaken. In particular, stirring speeds of 200-300 rpm were necessary to ensure the independence of release profile and agitation. Additionally, the dissolution medium may not provide sink conditions throughout the full dissolution process if pH variation does not take into account solubility differences between analogues. Ionic strength also influences release rates and attempts to examine the effects of pH must also control this variable. The proportion of cross-linking agent in the resin plays an important role. Increasing the cross-linking delays considerably the release of drug from the matrix and is a useful parameter in optimising controlled delivery. The loading efficiency of the resin is reduced, however, as the cations are excluded from parts of the resin due to a reduction in pore diameter. In contrast, the particle size of the resin has little influence upon loading efficiencies but larger particles significantly delay the release of drug. The effect of 0-n-acyl chain-length on the loading and release profiles was determined by molecular size. As groups increased in size the loading was inhibited and release rates were reduced. Again, this enables some control of release profiles but the approach is most suitable for drugs which are active at low doses which allow full use of these variations without the necessity for large amounts of resin in the delivery system.     

Towards sustained delivery of small molecular drugs using hydroxyapatite microspheres as the vehicle

The aim of this work is to explore the possibilities of using hydroxyapatite microspheres (HAP-MS) and polymer coated HAP-MS as the vehicles for the sustained release of small molecular drugs. The adsorption/desorption behaviors of model drug, doxycycline hydrochloride (Dox·HCl), on HAP-MS were systemically studied. Drug loaded HAP-MS was encapsulated by biodegradable PLGA using S/O/W emulsion–solvent evaporation method, and the in vitro drug release was tested. The adsorption kinetics of Dox·HCl onto HAP-MS fitted well to Freundlich model at lower drug concentrations, but when the HAP-MS was incubated in concentrated drug solutions higher than a critical concentration, precipitation of drug from solutions occurred. Rapid desorption or release of Dox·HCl from HAP-MS was observed. While, the release profile of Dox·HCl from PLGA coated microspheres showed steady slow drug release lasted for at least 7 days without obvious burst release. PLGA coated HAP-MS may provide a novel, injectable carrier for loading and long-period sustained release of small molecular, water-soluble drugs.     

Preparation and evaluation of a timolol maleate drug–resin ophthalmic suspension as a sustained-release formulation in vitro and in vivo

Abstract

The aim of this work was to assess the performance of resin as an ocular delivery system. Timolol maleate (TM) was chosen as the model drug and an ion exchange resin (IER) as the carrier. The drug–resin complex was prepared using an oscillation method and then characterized regarding particle size, zeta potential, morphology, and drug content. After in vitro drug release study and corneal permeation study were performed, in vivo studies were performed in New Zealand albino rabbits using a suspension with particles sized 4.8?±?1.2?μm and drug loading at 43.00?±?0.09 %. The results indicate that drug released from the drug–resin ophthalmic suspension permeated the cornea and displayed a sustained-release behavior. Drug levels in the ocular tissues after administration of the drug–resin ophthalmic suspension were significantly higher than after treatment with an eye drop formulation but were lower in body tissues and in the plasma. In conclusion, resins have great potential as effective ocular drug delivery carriers to increase ocular bioavailability of timolol while simultaneously reducing systemic drug absorption.     

Kinetics of removal of chromium from water and electronic process wastewater by ion exchange resins: 1200H, 1500H and IRN97H

The removal of chromium from aqueous solution by an ion exchange resin is described. Ion exchange resins 1200H, 1500H and IRN97H show a remarkable increase in sorption capacity for chromium, compared to other adsorbents. The adsorption process, which is pH dependent show maximum removal of chromium in the pH range 2-6 for an initial chromium concentration of 10mg/l. The metal ion adsorption obeyed linear, Langmuir and Freundlich isotherms. The adsorption of chromium on these cation exchange resins follows first-order reversible kinetics and pseudo-first-order kinetics. The intraparticle diffusion of chromium on ion exchange resins represents the rate-limiting step. The uptake of chromium by the ion exchange resins was reversible and thus have good potential for the removal/recovery of chromium from aqueous solutions. We conclude that such ion exchange resins can be used for the efficient removal of chromium from water and wastewater.     

Application of Ion Exchange Resin in Floating Drug Delivery System

The purpose of this study was to explore the application of low-density ion exchange resin (IER) Tulsion® 344, for floating drug delivery system (FDDS), and study the effect of its particle size on rate of complexation, water uptake, drug release, and in situ complex formation. Batch method was used for the preparation of complexes, which were characterized by physical methods. Tablet containing resin with high degree of crosslinking showed buoyancy lag time (BLT) of 5–8 min. Decreasing the particle size of resin showed decrease in water uptake and drug release, with no significant effect on the rate of complexation and in situ complex formation for both preformed complexes (PCs) and physical mixtures (PMs). Thus, low-density and high degree of crosslinking of resin and water uptake may be the governing factor for controlling the initial release of tablet containing PMs but not in situ complex formation. However, further sustained release may be due to in situ complex formation.     

Application of ion exchange resin in floating drug delivery system

The purpose of this study was to explore the application of low-density ion exchange resin (IER) Tulsion(R) 344, for floating drug delivery system (FDDS), and study the effect of its particle size on rate of complexation, water uptake, drug release, and in situ complex formation. Batch method was used for the preparation of complexes, which were characterized by physical methods. Tablet containing resin with high degree of crosslinking showed buoyancy lag time (BLT) of 5-8 min. Decreasing the particle size of resin showed decrease in water uptake and drug release, with no significant effect on the rate of complexation and in situ complex formation for both preformed complexes (PCs) and physical mixtures (PMs). Thus, low-density and high degree of crosslinking of resin and water uptake may be the governing factor for controlling the initial release of tablet containing PMs but not in situ complex formation. However, further sustained release may be due to in situ complex formation.     

Preparation and in vitro release of dual-drug resinates containing equivalent content dextromethorphan and diphenhydramine

The dual-drug resinate containing equivalent content of dextromethorphan hydrobromide (DTM) and diphenhydramine hydrochloride (DPH) was developed and characterized. To achieve this specific resinate, a procedure of simultaneous dual-drug loading using loading solutions composed of different proportions of DTM and DPH was performed and a dual-drug loading diagram was constructed to determine the equivalent drug loading solution (ELS) and also the estimated equivalent drug content (EQC). The effects of resin crosslinkage, overall drug concentration of the loading solution, and temperature during drug loading on the values of ELS and EQC were assessed. The increased overall drug concentration from 0.25 to 1.0% w/v elevated the EQC values from 18 to 35% w/w for low crosslinked resins (Dowex 50W × 2 and × 4), and from 18 to 27% w/w for high crosslinked resin (Dowex 50W × 8). It also changed the values of ELS from 0.50 to 0.48 for the low crosslinked resins, and 0.50 to 0.55 for the high crosslinked resin. For the high crosslinked resin, the applied heat from 35 to 65°C further increased the values of EQC from 27 to 32% w/w, and changed the values of ELS in the reverse direction from 0.55 to 0.48. However, the heat did not exert significant effects on the values of EQC and ELS for the low crosslinked resins. Different batches of dual-drug resinates prepared from the determined ELS provided the resultant resinates with equivalent contents of DTM and DPH which were very close to the estimated EQC. The drug release from the resinates was performed in 0.05, 0.1, 0.2, and 0.4 N of KCl solutions. The increased ionic strength generally accelerated the release of both drugs except for 0.4 N KCl solution in which the drug release from the resinates of high crosslinkage was decreased. The congestion on the outward movement of drugs through the high crosslinked matrix might cause the delay of drug release. In conclusion, the release study demonstrated that the dual-drug resinate using a suitable crosslinked resin could be used for extended delivery of two combined drugs with the equivalent therapeutic dose.     

Comparison of soluble and immobilized acetate for removing Pb from contaminated soil

Five lead (Pb) contaminated soils were used in a laboratory and modeling study to examine the effects of soluble and immobilized acetate on Pb removal from a contaminated soil as a function of pH. Soluble acetate was added as sodium acetate; immobilized acetate was added in the form of a cation exchange resin. For comparative purposes, Pb adsorption with no acetate also was measured as a function of pH. A surface complexation modeling framework was used to interpret experimental data. Experimental results showed the cation exchange resin was much more effective than soluble acetate in removing Pb from soils due to a strong affinity of the resin for Pb. In addition, concentrations of soluble Pb in resin/soil slurry were very low, minimizing the pollution threat if discharged. As deduced from modeling studies, soluble acetate performed poorly compared to the resin, in part, due to adsorption of the soluble PbAc(+) complex. The effectiveness of both soluble and immobilized acetate was diminished below pH 4 as a result of competition by H(+) for acetate. Modeling results based on resin affinity for Pb compare well with experimental data for resin/soil mixtures, suggesting that Pb partitioning in resin/soil mixtures may be predicted reasonably well if soil/Pb and resin/Pb partitioning are known. Thus, the modeling approach may be used as a screening tool to determine the performance of alternative resins.     

啶虫脒在超高交联吸附树脂上的吸附及脱附性能研究

本文从动态和静态的角度研究了均苯四甲酸酐修饰的超高交联吸附树脂（PMAR）和1,2,4-苯三酸酐修饰的超高交联吸附树脂（TMAR）对啶虫脒的吸附和脱附行为。结果表明：两种树脂对啶虫眯的吸附和脱附效果都比较好,TMAR的静态吸附量为470．9mg·g^-1干树脂,饱和吸附量为562．7mg·g^-1干树脂;PMAR的静态吸附量为453．4mg·g^-1干树脂,饱和吸附量为559．1mg·g^-1干树脂。两种树脂都易于脱附,用2mol·L^-1 HCl：乙醇（体积比1：1）作脱附剂,温度323K,脱附剂体积为9．5BV（床体积）时,PMAR的脱附率为98．13％,TMAR的脱附率为99．83％。     

Preparation and In Vitro Release of Dual-Drug Resinates Containing Equivalent Content Dextromethorphan and Diphenhydramine

ABSTRACT

The dual-drug resinate containing equivalent content of dextromethorphan hydrobromide (DTM) and diphenhydramine hydrochloride (DPH) was developed and characterized. To achieve this specific resinate, a procedure of simultaneous dual-drug loading using loading solutions composed of different proportions of DTM and DPH was performed and a dual-drug loading diagram was constructed to determine the equivalent drug loading solution (ELS) and also the estimated equivalent drug content (EQC). The effects of resin crosslinkage, overall drug concentration of the loading solution, and temperature during drug loading on the values of ELS and EQC were assessed. The increased overall drug concentration from 0.25 to 1.0% w/v elevated the EQC values from 18 to 35% w/w for low crosslinked resins (Dowex 50W × 2 and × 4), and from 18 to 27% w/w for high crosslinked resin (Dowex 50W × 8). It also changed the values of ELS from 0.50 to 0.48 for the low crosslinked resins, and 0.50 to 0.55 for the high crosslinked resin. For the high crosslinked resin, the applied heat from 35 to 65°C further increased the values of EQC from 27 to 32% w/w, and changed the values of ELS in the reverse direction from 0.55 to 0.48. However, the heat did not exert significant effects on the values of EQC and ELS for the low crosslinked resins. Different batches of dual-drug resinates prepared from the determined ELS provided the resultant resinates with equivalent contents of DTM and DPH which were very close to the estimated EQC. The drug release from the resinates was performed in 0.05, 0.1, 0.2, and 0.4 N of KCl solutions. The increased ionic strength generally accelerated the release of both drugs except for 0.4 N KCl solution in which the drug release from the resinates of high crosslinkage was decreased. The congestion on the outward movement of drugs through the high crosslinked matrix might cause the delay of drug release. In conclusion, the release study demonstrated that the dual-drug resinate using a suitable crosslinked resin could be used for extended delivery of two combined drugs with the equivalent therapeutic dose.     

Removal of chromium from water and wastewater by ion exchange resins

Removal of chromium from water and wastewater is obligatory in order to avoid water pollution. Batch shaking adsorption experiments were carried out to evaluate the performance of IRN77 and SKN1 cation exchange resins in the removal of chromium from aqueous solutions. The percentage removal of chromium was examined by varying experimental conditions viz., dosage of adsorbent, pH of the solution and contact time. It was found that more than 95% removal was achieved under optimal conditions. The adsorption capacity (k) for chromium calculated from the Freundlich adsorption isotherm was found to be 35.38 and 46.34 mg/g for IRN77 and SKN1 resins, respectively. The adsorption of chromium on these cation exchange resins follows the first-order reversible kinetics. The ion exchange resins investigated in this study showed reversible uptake of chromium and, thus, have good application potential for the removal/recovery of chromium from aqueous solutions.     

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.     

Design of novel polymeric adsorbents for metal ion removal from water using computer-aided molecular design

Heavy metals in drinking water act as contaminants that can cause serious health problems. These metal ions in drinking water are generally removed using cation exchange resins that are used as adsorbents. Generally, chelating resins with limited adsorption capacity are commercially available. Manufacturing novel resin polymers with enhanced adsorption capacity of metal ion requires ample experimental efforts that are expensive as well as time consuming. To overcome these difficulties, application of computer-aided molecular design (CAMD) will be an efficient way to develop novel chelating resin polymers. In this paper, CAMD based on group contribution method (GCM) has been used to design novel resins with enhanced adsorption capability of removing heavy metal ions from water. A polymer consists of multiple monomer units that repeat in a polymer chain. Each repeat unit of the polymer can be subdivided into different structural and functional groups. The adsorption mechanism of heavy metals on resin depends on the difference between activities in adsorbents and the bulk fluid phase. The contribution of the functional groups in the adsorption process is found by estimating the activity coefficient of heavy metal in the solid phase and bulk phase using a modified version of the UNIFAC GCM. The interaction parameters of the functional groups are first determined and then they are used in a combinatorial optimization method for CAMD of novel resin polymers. In this work, designs of novel resin polymers for the removal of Cu ions from drinking water are used as a case study. The proposed new polymer resin has an order of magnitude higher adsorption capacity compared to conventional resin used for the same purpose.     

Reformulation of a codeine phosphate liquid controlled-release product

Background: Ion-exchange resins have been successfully used to create drug formulations providing controlled drug release that are easy to swallow, are sufficiently stable, and have good taste-masking characteristics. The objective of the present study was to replace the ion-exchange resin in a proven delayed release codeine preparation with a new resin able to provide the beneficial properties of the original formulations without the need for Eudragit coating to comply with modern manufacturing regulations. Methods: Nine cationic exchangers with different particle meshes, form, and pore structures were optimally loaded with codeine and their respective in vitro codeine release profiles were compared using the USP XXIII paddle method. Results: The most favorable release profiles were obtained with Amberlite IR 69 F and with Dowex 50 × 8?100. The former was used to prepare the formulated drug–resin complexes as it was available in a pharmaceutically pure form. Both, the cough syrup and concentrate formulations exhibited drug release profiles equivalent to the nonformulated drug–resin complex. These profiles as well as initial free codeine levels, the purity, and the identity were moreover maintained for a storage period of at least 6 months. Conclusion: The in vitro dissolution profiles demonstrated that the use of ion exchanger is most suitable for the development of sustained release codeine formulations.     

Evaluation of intratympanic formulations for inner ear delivery: methodology and sustained release formulation testing

A convenient and efficient in vitro diffusion cell method to evaluate formulations for inner ear delivery via the intratympanic route is currently not available. The existing in vitro diffusion cell systems commonly used to evaluate drug formulations do not resemble the physical dimensions of the middle ear and round window membrane. The objectives of this study were to examine a modified in vitro diffusion cell system of a small diffusion area for studying sustained release formulations in inner ear drug delivery and to identify a formulation for sustained drug delivery to the inner ear. Four formulations and a control were examined in this study using cidofovir as the model drug. Drug release from the formulations in the modified diffusion cell system was slower than that in the conventional diffusion cell system due to the decrease in the diffusion surface area of the modified diffusion cell system. The modified diffusion cell system was able to show different drug release behaviors among the formulations and allowed formulation evaluation better than the conventional diffusion cell system. Among the formulations investigated, poly(lactic-co-glycolic acid)–poly(ethylene glycol)–poly(lactic-co-glycolic acid) triblock copolymer systems provided the longest sustained drug delivery, probably due to their rigid gel structures and/or polymer-to-cidofovir interactions.     

An approach to controlled-release dosage form of propranolol hydrochloride

It is possible to release a drug with only limited diffusion from a membrane-coated system using osmotic pumping. In this study, a propranolol osmotic pump was produced by coating the core tablets with cellulose acetate. The effects of membrane thickness, pore size, and stirring rate on the release rate of propranolol hydrochloride were studied. It was found that the thickness of cellulose acetate membrane had a profound effect on the release rate of propranolol hydrochloride from the membrane-coated tablets. The results showed that, when the membrane thickness increased, the release rate of propranolol decreased. The drug release follows a zero-order release when the delivery orifice is between 200 and 800 μm, but when the delivery orifice size is increased to 1000μm, the release kinetic is abnormal. Fluid dynamics have an important effect on the delivery rate of propranolol from this device; the delivery rate increases as a function of the fluid flow. The drug release is higher under a turbulent condition with high rate of stirring.     

Bioactive silica-based nanomaterials for doxorubicin delivery: Evaluation of structural properties associated with release rate

This study investigated the use of a novel particle-type formulation, composed of a sol–gel derived bioactive silica-poly(dimethylsiloxane) composite containing calcium and phosphate, as a slow release delivery system for an anticancer drug (doxorubicin hydrochloride, DOX). DOX in the solution form was in situ incorporated into the composite network during the sol–gel process. The DOX loaded-formulation was immersed in a simulated body fluid (SBF) having ion concentrations and a pH value nearly equal to those of human blood plasma. The effect of different drug loads and particle sizes — on the release profiles in such biomimetic conditions was studied. The bioactivity was examined in vitro with respect to the ability of hydroxyapatite layer to form on the surface of residual DOX-loaded formulation as a result of contact with SBF. The infrared absorption spectra, scanning electron microscopy, nitrogen gas adsorption/desorption, and X-ray powder diffraction studies were conducted before and after contact of the formulation with SBF. The results show that all the DOX-loaded formulations are characterized by mesoporosity with the uniform pore-size-distribution. The release profiles of DOX consisted of two sequential zero order-controlled stages with distinctly different release rates. After 20 days of DOX release, a semicrystalline carbonated hydroxyapatite with a highly developed porous structure was formed, indicative of their bioactive character. Furthermore, these new covered-particle-type formulations released DOX over 1 month at a constant rate.