Initial Drug Concentration Research Articles

Designing a Novel Drug Delivering Nerve Guide: A Preliminary Study

Peripheral nerve lesions caused by trauma often require the removal of the injured segment of nerve and subsequent surgical repair. Nerve injuries that produce large gaps require a “bridge” to guide axon growth. Autografts are currently the gold standard for bridging that gap but they have drawbacks including donor site morbidity and limited donor sites. Surgically implanting a nerve guidance conduit is an alternative solution to grafting. The conduits can provide guidance for the regenerating axons and allow for tension free bridging. We present a bioresorbable drug delivery conduit that relies on the mechanics of diffusion to locally deliver neurotrophins to the regeneration site. The drug delivery conduit was fabricated using solvent casting and tested for release kinetics using dextran and nerve growth factor. A drug diffusion model was also developed to test the reliability and predictability of our device, and finally the bioactivity of the released media was evaluated by measuring neurite extension in dorsal root ganglia (DRG). The results of the in vitro drug release tests showed that diffusion of drug through our conduits could be tuned by varying the hole size and reservoir size. Linear scaling can be achieved by modifying the initial concentration of drug loaded in the reservoir. The drug delivery nerve conduit was able to release bioactive NGF for 8 days and enhance DRG neurite extension. The drug delivery nerve conduit can release bioactive drugs predictably and has the potential to improve nerve regeneration following a peripheral nerve injury.

Grafting of sulfamethoxazole on acrylic acid−vinyl methyl ketone copolymer using the schiff base reaction−application as a drug delivery system

ABSTRACTA series of poly(acrylic acid-co-methylvinylketone–graft–sulfamethoxazole)(AVMDS) species was synthesized for drug carrier applications. The synthesis involved two steps: copolymerization of acrylic acid(AA) with methyl vinyl ketone(MVK) through the free radical route and subsequent grafting of the sulfamethoxazole (SMX) onto the copolymer via the Schiff base reaction of the primary amine of SMX with the carbonyl groups of the MVK units. The structures and properties of the materials were characterized by nuclear magnetic resonance(NMR), X-ray diffraction(XRD), differential scanning calorimetry(DSC), and scanning electronic microscopy (SEM). An in-vitro cytotoxicity test of the drug-carrier systems via MTT assay revealed no significant cytotoxic effect at concentrations up to 100 µg · ml−1. The dynamic release of SMX from these systems through a retro-imidation reaction (inverse Schiff base reaction) was investigated in depth, where the diffusion through the polymer matrix, the enhancement of the water solubility of SMX, the influence of the initial drug concentration, the pH of the medium, and the effect of the degree of swelling of the polymer matrix on the release dynamics were evaluated. The AVMGS4 and AVMGS1 drug carrier systems containing 3.58 and 1.18 wt% of SMX were the best performing systems.

Cathinone stability in authentic urine specimens

PurposeSynthetic cathinones are encountered in a variety of antemortem and postmortem forensic toxicology investigations. Earlier experimental studies using fortified urine have evaluated analyte, temperature and pH-dependent variables associated with their stability. The purpose of this study was to compare experimental findings with those obtained using authentic urine from cathinone users. MethodsIn this report we compare cathinone concentrations in 180 authentic unpreserved urine specimens, following known periods of refrigerated storage. These findings are compared with previously published experimental data using fortified drug-free urine. Liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS) was used to target 22 cathinones. Quantitative results were compared in urine specimens (pH 4.5–10) following 5–17 months of storage. ResultsThe 180 specimens resulted in 164 quantitative findings involving α-PVP, ethylone, methylone, MDPV and pentylone. Initial drug concentrations ranged from 25ng/mL to over 100,000ng/mL. Upon reanalysis, the percentage of drug remaining (0–119%) was correlated with storage time and specimen pH. The ability to reconfirm original results was not correlated with storage time. Instead, specimen pH was far more predictive. The relationship between initial and final drug concentration was highly pH-dependent, yielding significant correlations for α-PVP, ethylone and methylone, particularly under acidic conditions. ConclusionsThese results are in good agreement with experimental findings and highlight the critical importance of specimen pH, rather than conventional time dependent variables, when considering cathinone stability in biological samples. The potential for pre-analytical changes in cathinone concentrations must be carefully considered when interpreting their results.

ITCA 650

ITCA 650

When drugs plasticize film coatings: Unusual formulation effects observed with metoprolol and Eudragit RS

Metoprolol tartrate and metoprolol free base loaded pellet starter cores were coated with Eudragit RS, plasticized with 25% triethyl citrate (TEC). The initial drug loading and coating level were varied from 10 to 40 and 0 to 20%, respectively. Drug release was measured in 0.1 N HCl and phosphate buffer pH 7.4. The water uptake and swelling kinetics, mechanical properties and TEC leaching of/from coated pellets and/or thin, free films of identical composition as the film coatings were monitored. The following unusual tendencies were observed: (i) the relative drug release rate from coated pellets increased with increasing initial drug content, and (ii) drug release from pellets was much faster for metoprolol free base compared to metoprolol tartrate, despite its much lower solubility (factor >70). These phenomena could be explained by plasticizing effects of the drug for the polymeric film coatings. In particular: 1) Metoprolol free base is a much more potent plasticizer for Eudragit RS than the tartrate, leading to higher film permeability and overcompensating the pronounced differences in drug solubility. Also, Raman imaging revealed that substantial amounts of the free base migrated into the film coatings, whereas this was not the case for the tartrate. 2) The plasticizing effects of the drug for the film coating overcompensated potential increasing limited solubility effects when increasing the initial drug loading from 10 to 40%. In summary, this study clearly demonstrates how important the plasticization of polymeric controlled release film coatings by drugs can be, leading to unexpected formulation effects.

Miscibility of poly(acrylic acid)/poly(methyl vinyl ketone) blend and in vitro application as drug carrier system

ABSTRACTA series of poly(acrylic acid)/poly(methyl vinyl ketone) (PAA/PMVK) blends with different compositions were prepared by the solvent casting method. The miscibility of this pair of polymers was investigated by differential scanning calorimetry(DSC), Fourier transform infra-red (FTIR) and X-Ray diffraction (XRD) techniques. An in-vitro cytotoxicity test of the drug-carrier system via MTT (3-(4,5-demethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay revealed no significant cytotoxic effects at concentrations up to 100 µg· ml−1. The STX/PAA-50 drug carrier systems were also prepared by solvent casting of solutions containing the sulfamethoxazole (STX) used as drug model and PAA/PMVK blend in N.N-dimethylformamide then crosslinked with acidified ethylene glycol. The release dynamic of STX from the prepared hydrogels was investigated in which the diffusion through the polymer matrix, the enhancement of the water solubility of STX, the influence of the initial drug concentration, the pH of the medium, and the effect of the degree of swelling of the polymer matrix on the release dynamic was evaluated. According to the total gastrointestinal transit time estimated by Belzer, the estimate distribution of STX released in the different organs indicated that the performance is obtained with the drug – carrier-system containing equal ratios of polymer and 10 wt% of STX (STX-10/PAA-50).

Photocatalytic degradation of diclofenac using TiO2–SnO2 mixed oxide catalysts

ABSTRACTThe complex nature of diclofenac limits its biological degradation, posing a serious threat to aquatic organisms. Our present work aims to eliminate diclofenac from wastewater through photocatalytic degradation using TiO2–SnO2 mixed-oxide catalysts under various operating conditions such as catalyst loading, initial diclofenac concentration and initial pH. Different molar ratios of Ti–Sn (1:1, 5:1, 10:1, 20:1 and 30:1) were prepared by the hydrothermal method and were characterized. The results indicated that addition of Sn in small quantity enhances the catalytic activity of TiO2. Energy Band gap of the TiO2–SnO2 catalysts was found to increase with an increase in Tin content. TiO2–SnO2 catalyst with a molar ratio of 20:1 was found to be the most effective when compared to other catalysts. The results suggested that initial drug concentration of 20 mg/L, catalyst loading of 0.8 g/L and pH 5 were the optimum operating conditions for complete degradation of diclofenac. Also, the TiO2–SnO2 catalyst was effective in complete mineralization of diclofenac with a maximum total organic carbon removal of 90% achieved under ultraviolet irradiation. The repeatability and stability results showed that the TiO2–SnO2 catalyst exhibited an excellent repeatability and better stability over the repeated reaction cycles. The photocatalytic degradation of diclofenac resulted in several photoproducts, which were identified through LC-MS.

Preparation and evaluation of injectable Rasagiline mesylate dual-controlled drug delivery system for the treatment of Parkinson’s disease

A microsphere–gel in situ forming implant (MS–Gel ISFI) dual-controlled drug delivery system was applied to a high water-soluble small-molecule compound Rasagiline mesylate (RM) for effective treatment of Parkinson’s disease. This injectable complex depot system combined an in situ phase transition gel with high drug-loading and encapsulation efficiency RM–MS prepared by a modified emulsion-phase separation method and optimized by Box–Behnken design. It was evaluated for in vitro drug release, in vivo pharmacokinetics, and in vivo pharmacodynamics. We found that the RM-MS-Gel ISFI system showed no initial burst release and had a long period of in vitro drug release (60 days). An in vivo pharmacokinetic study indicated a significant reduction (p < .01) in the initial high plasma drug concentration of the RM–MS–Gel ISFI system compared to that of the single RM–MS and RM–in situ gel systems after intramuscular injection to rats. A pharmacodynamic study demonstrated a significant reduction (p < .05) in 6-hydroxydopamine-induced contralateral rotation behavior and an effective improvement (p < .05) in dopamine levels in the striatum of the lesioned side after 28 days in animals treated with the RM–MS–Gel ISFI compared with that of animals treated with saline. MS-embedded in situ phase transition gel is superior for use as a biodegradable and injectable sustained drug delivery system with a low initial burst and long period of drug release for highly hydrophilic small molecule drugs.

Stability of 2 mg/mL Adenosine Solution in Polyvinyl Chloride and Polyolefin Infusion Bags.

Adenosine is a potent endogenous mediator of vasodilation. Compounded sterile solutions of adenosine are used in cardiac catheterization lab to perform stress tests on the heart. These tests are used to determine the fractional flow reserve (FFR) and are commonly used in the management and diagnosis of cardiovascular conditions. The purpose of this study was to assess the physical and chemical stability of 2 mg/mL adenosine in 0.9% Sodium Chloride Injection, USP in polyvinyl chloride [PVC]) and polyolefin infusion bags stored at room temperature (20°C-25°C) and under refrigeration (2°C-8°C). The compounding and analytical methods used in this study were very similar to those described in the prior publications from the authors' laboratory. To ensure a uniform starting concentration of all stability samples, a batch of 2 mg/mL adenosine solution was prepared and then packaged into empty PVC and polyolefin infusion bags. These stability samples were prepared in triplicate for each bag type and storage temperature (a total of 12 samples). The infusion bag samples were assessed for stability immediately after preparation and after 1 day, 3 days, 7 days, and 14 days. At each time point, the infusion bags were first visually inspected against a light background for color change, clarity, and particulates. Aliquots were drawn from each sample at each time point for pH analysis and high-performance liquid chromatography (HPLC) analysis. Over 14 days of storage at room temperature or refrigeration, no considerable change in visual appearance or pH was observed in any bags. All samples retained 90% to 110% of the initial drug concentration. No significant degradation peaks were observed in the HPLC chromatograms.

A simple way for targeted delivery of an antibiotic: In vitro evaluation of a nanoclay-based composite.

The sodium-modified form of fluorohectorite nanoclay (NaFh) is introduced as a potential drug carrier, demonstrating its ability for the controlled release of the broad-spectrum antibiotic Ciprofloxacin through in vitro tests. The new clay-drug composite is designed to target the local infections in the large intestine, where it delivers most of the incorporated drug thanks to its pH-sensitive behavior. The composite has been conceived to avoid the use of coating technology and to decrease the side-effects commonly associated to the burst-release of the ciprofloxacin at the stomach level. NaFh was obtained from lithium-fluorohectorite by ion exchange, and its lack of toxicity was demonstrated by in vivo studies. Ciprofloxacin hydrochloride (Cipro) was encapsulated into the clay at different values of the pH, drug initial concentration, temperature and time. Systematic studies by X-ray diffraction (XRD), infrared and visible spectrophotometry (FT-IR and UV-vis), and thermal analysis (TGA) indicated that the NaFh host exhibits a high encapsulation efficiency for Cipro, which reaches a 90% of the initial Cipro in solution at 65 oC, with initial concentration of drug in solution of 1.36 x 10−2 mol L-1 at acid pH. XRD revealed that a true intercalation of Cipro takes place between clay layers. TG showed an increased thermal stability of the drug when intercalated into the clay, as compared to the “free” Cipro. IR suggested a strong clay-Cipro interaction via ketone group, as well as the establishment of hydrogen bonds between the two materials. In vitro drug release tests revealed that NaFh is a potentially efficient carrier to deliver Cipro in the large intestine, where the release process is mediated by more than just one mechanism.

Evaluation of Specific Administering Devices for Antineoplastic Drugs Compounded in Syringes in Paediatry: Methodology Proposal.

Purpose The aims of this study were to propose a simple methodology to assess the rinsing volume of syringe extension sets and to compare several marketed devices. Methods A UV-spectrophotometry assay using quinine hydrochloride as drug substitute was developed. Quinine concentration ranged from 20 to 200 µg/ml. The assay was validated with the accuracy profile method and tested on five different assemblies (device+extension sets) with different dead-space volumes (1.28-2.80 ml) and at two different quinine concentrations (0.3 and 8.0 mg/ml). Rinsing was performed stepwise with water for injection until reaching an undetectable quinine concentration. After fitting the data with a Weibull model, assemblies were compared with an ANOVA performed on ranks (GraphPad, La Jolla, USA). Results The within-day and between-day precision ranges were 0.39-0.81 and 0.48-0.84%, respectively. The lower limit of quantification was 4.26 µg/ml. The volume required to completely rinse the infusion line was different according to the initial drug concentration and to the device assessed: from 6 to 10 ml for a low quinine concentration and from 7 to 17 ml for a high quinine concentration. Conclusion This study shows that a simple, cheap and easy-to-use methodology may be used to assess the rinsing volume of syringe extension sets. The rinsing volume is different according to the tested device.

An environmentally friendly electrochemical reactor for the degradation of organic pollutants in the total absence of a liquid electrolyte: A case study using diclofenac as a model pollutant

In order to fabricate an environmentally friendly electrochemical reactor for the degradation of organic pollutants in the total absence of a liquid electrolyte, fluid-permeable anodes (FPAs) composed of mixed oxide-covered mesh electrodes (MOMEs) containing cobalt and nickel, denoted as MOME-Ni(x)Co(1−x)Oy where x=0.9, 0.8 and 0.3, were prepared by thermal decomposition using the slow cooling rate method on a stainless-steel fine-mesh support. The electrochemical degradation of diclofenac (model pollutant) in electrolyte-free water was carried out in batch mode using a solid polymer electrolyte (SPE) electrochemical reactor. For the different MOME compositions, their properties were investigated as a function of the initial drug concentration (IDC) and the electric current density (j). The effects of IDC and j on the degradation of diclofenac were quite similar according to analyses performed using UV–vis and HPLC techniques, wherein it was verified for the different MOMEs that the degradation rate of diclofenac increased with increasing j and IDC. The electrode composition (Ni percentage) exerted only a minor influence on the degradation of diclofenac. On the other hand, a strong influence of j and IDC on the degradation was verified. It was also verified that an increase in IDC resulted in higher values of total current efficiency (TCE) measured for the combustion reaction. Taking into account that the lowest values of the electrical energy per order (EEO) were obtained for MOME-Ni(0.3)Co(0.7)Oy, it was concluded that the best overall performance for the electrochemical degradation of diclofenac in electrolyte-free water was achieved using this electrode composition.

Self-assembled polypeptide nanoparticles for intracellular irinotecan delivery

In this research poly(l-lysine)-b-poly(l-leucine) (PLys-b-PLeu) polymersomes were developed. It was shown that the size of nanoparticles depended on pH of self-assembly process and varied from 180 to 650nm. The biodegradation of PLys-b-PLeu nanoparticles was evaluated using in vitro polypeptide hydrolysis in two model enzymatic systems, as well as in human blood plasma. The experiments on the visualization of cellular uptake of rhodamine 6g-loaded and fluorescein-labeled nanoparticles were carried out and the possibility of their penetration into the cells was approved. The cytotoxicity of polymersomes obtained was tested using three cell lines, namely, HEK, NIH-3T3 and A549. It was shown that tested nanoparticles did not demonstrate any cytotoxicity in the concentrations up to 2mg/mL. The encapsulation of specific to colorectal cancer anti-tumor drug irinotecan into developed nanocontainers was performed by means of pH gradient method. The dispersion of drug-loaded polymersomes in PBS was stable at 4°C for a long time (at least 1month) without considerable drug leakage. The kinetics of drug release was thoroughly studied using two model enzymatic systems, human blood serum and PBS solution. The approximation of irinotecan release profiles with different mathematical drug release models was carried out and allowed identification of the release mechanism, as well as the morphological peculiarities of developed particles. The dependence of encapsulation efficiency, as well as maximal loading capacity, on initial drug concentration was studied. The maximal drug loading was found as 320±55μg/mg of polymersomes. In vitro anti-tumoral activity of irinotecan-loaded polymersomes on a colon cancer cell line (Caco-2) was measured and compared to that for free drug.

Novel Chitosan Microparticles for Sequestration of Overdosed Drug

Chitosan microparticles were synthesized by crosslinking chitosan and glycidyl trimethylammonium chloride modified chitosan inside the reverse micelles of Span and Tween 80. The particles were of uniform size with the average diameter of 10 μm. The particles swelled almost twice the original size in 20 min when dispersed in a buffer solution of pH 7.4. The feasibility of chitosan microparticles as drug sequestrant was tested using propafenone as the model drug. The particles sequestered free propafenone from a buffer solution of pH 7.4. In 20 min unmodified chitosan and modified chitosan microparticles sequestered 53% and 51.5% of the free drug respectively. The amount of drug sequestered increased with increase in the initial free drug concentration. The presence of normal saline also improved propafenone sequestration.

Abstract 4205: Intracellular pharmacokinetics of 5FU and palbociclib: Uptake and efflux in disaggregated cells and 3D models

Abstract Introduction: Pre-clinical drug development does not routinely assess drug penetration beyond use of the human intestinal Caco-2 cell line as an in vitro model of the intestinal barrier to evaluate potential drug absorption. Detailed in vivo tumour pharmacokinetic (PK) studies are unusual. However, the ability of a drug to reach its target plays a key role in drug efficacy. Here we present a methodology to study drug PK in disaggregated cells and in a 3D cell culture model (spheroids) using 5FU and palbociclib. The comparison of these 2 drugs is of interest taking into account their different mechanisms and chemical properties, logP 0.58 and 2.12 respectively. Knowledge of cellular uptake and efflux in disaggregated cells and 3D models together with intracellular binding characteristics is vital to optimise a better drug delivery. Experimental procedures: MCF-7 and DLD-1 cells were used for cellular and spheroid experiments. Spheroid growth was optimized to produce a spheroid of 300-400µm diameter at day 4. Drug uptake: 1x106 cells or 30 spheroids/time point were exposed to 10µM 5FU or 0.1µM of palbociclib for different time durations. For 5FU, drug uptake at 100µM was also monitored to detect 5FU metabolites. Drug efflux: 1x106 cells were exposed first to 100µM 5FU or 0.1µM of palbociclib for 60min then, drug media removed, substituted by fresh media and sample over a 4h period. Drug concentration inside cells and in the fresh media was measured. Drug concentrations were measured using HPLC-Tandem Mass Spectrometry. Each experiment was carried out in triplicate. Results: 5FU achieves intracellular steady state within 5-10min in cells and spheroids with equal concentrations inside and outside the cell/spheroids. Intracellular metabolites of 5FU were only seen with 100µM treatment and had a similar PK characteristics to 5FU. 5FU drug efflux experiments showed that efflux occurred rapidly within 5min achieving a new equilibrium with 30% of 5FU remaining inside the cells. 5FUrd was also detected extracellularly after 1h in the fresh media, showing that cells have both 5FU and metabolite efflux. In contrast, palbociclib cellular uptake had an initial intracellular drug concentration peak at 5-10min which then plateaued. Interestingly, total intracellular concentrations of palbociclib were over 30 times higher compared to the external media drug at steady state. Spheroid and efflux experiments of palbociclib are on-going and will be presented. Conclusions: Our results suggest that both drugs penetrate quickly in cancer cells. Palbociclib intracellular concentrations were 30 times higher than the external media suggesting excessive intracellular binding while 5FU achieve equal concentrations between the inside and outside of the cell. These data and methodology may be useful to allow generation of mathematical models to improve drug delivery design. Citation Format: Maria Jove, Paul Loadman, Jade Spencer, Lava Sulayman, Jo Wicks, Amanda Race, Chris Twelves. Intracellular pharmacokinetics of 5FU and palbociclib: Uptake and efflux in disaggregated cells and 3D models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4205. doi:10.1158/1538-7445.AM2017-4205

Drug Release as a function of bioactivity, incubation regime, liquid, and initial load: Release of bortezomib from calcium phosphate-containing silica/collagen xerogels.

The ability of silica-/collagen-based composite xerogels to act as drug delivery systems was evaluated by taking into account the initial drug concentration, bioactivity of the xerogels, liquid, and incubation regime. The proteasome inhibitor bortezomib was chosen as a model drug, used for the systemic treatment of multiple myeloma. Incubation during 14 days in phosphate-buffered saline (PBS) or simulated body fluid (SBF) showed a weak initial burst and was identified to be of first order with subsequent release being independent from the initial load of 0.1 or 0.2 mg bortezomib per 60 mg monolithic sample. Faster drug release occurred during incubation in SBF compared to PBS, and during static incubation without changing the liquid, compared to dynamic incubation with daily liquid changes. Drug-loaded xerogels with hydroxyapatite as a third component exhibited enhanced bioactivity retarding drug release, explained by formation of a surface calcium phosphate layer. The fastest release of 50% of the total drug load was observed for biphasic xerogels after 7 days during dynamic incubation in SBF. As a result, the presented concept is suitable for the intended combination of the advantageous bone substitution properties of xerogels and local application of drugs exemplified by bortezomib. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1165-1173, 2018.

Supercritical antisolvent co-precipitation of rifampicin and ethyl cellulose

Rifampicin-loaded submicron-sized particles were prepared through supercritical anti-solvent process using ethyl cellulose as polymeric encapsulating excipient. Ethyl acetate and a mixture of ethyl acetate/dimethyl sulfoxide (70/30 and 85/15) were used as solvents for both drug and polymeric excipient. When ethyl acetate was used, rifampicin was crystallized separately without being embedded within the ethyl cellulose matrix while by using the ethyl acetate/dimethyl sulfoxide mixture, reduced crystallinity of the active ingredient was observed and a simultaneous precipitation of ethyl cellulose and drug was achieved. The effect of solvent/CO2 molar ratio and polymer/drug mass ratio on the co-precipitates morphology and drug loading was investigated. Using the solvent mixture, co-precipitates with particle sizes ranging between 190 and 230nm were obtained with drug loading and drug precipitation yield from respectively 8.5 to 38.5 and 42.4 to 77.2% when decreasing the ethyl cellulose/rifampicin ratio. Results show that the solvent nature and the initial drug concentrations affect morphology and drug precipitation yield of the formulations. In vitro dissolution studies revealed that the release profile of rifampicin was sustained when co-precipitation was carried out with the solvent mixture. It was demonstrated that the drug to polymer ratio influenced amorphous content of the SAS co-precipitates. Differential scanning calorimetry thermograms and infrared spectra revealed that there is neither interaction between rifampicin and the polymer nor degradation of rifampicin during co-precipitation. In addition, stability stress tests on SAS co-precipitates were carried out at 75% relative humidity and room temperature in order to evaluate their physical stability. SAS co-precipitates were X-ray amorphous and remained stable after 6months of storage. The SAS co-precipitation process using a mixture of ethyl acetate/dimethyl sulfoxide demonstrates that this strategy can be successful for controlling rifampicin delivery.

Mathematical model to analyze the dissolution behavior of metastable crystals or amorphous drug accompanied with a solid-liquid interface reaction

Metastable crystals and the amorphous state of poorly water-soluble drugs in solid dispersions (SDs), are subject to a solid-liquid interface reaction upon exposure to a solvent. The dissolution behavior during the solid-liquid interface reaction often shows that the concentration of drugs is supersaturated, with a high initial drug concentration compared with the solubility of stable crystals but finally approaching the latter solubility with time. However, a method for measuring the precipitation rate of stable crystals and/or the potential solubility of metastable crystals or amorphous drugs has not been established. In this study, a novel mathematical model that can represent the dissolution behavior of the solid-liquid interface reaction for metastable crystals or amorphous drug was developed and its validity was evaluated. The theory for this model was based on the Noyes-Whitney equation and assumes that the precipitation of stable crystals at the solid-liquid interface occurs through a first-order reaction. Moreover, two models were developed, one assuming that the surface area of the drug remains constant because of the presence of excess drug in the bulk and the other that the surface area changes in time-dependency because of agglomeration of the drug. SDs of Ibuprofen (IB)/polyvinylpyrrolidone (PVP) were prepared and their dissolution behaviors under non-sink conditions were fitted by the models to evaluate improvements in solubility. The model assuming time-dependent surface area showed good agreement with experimental values. Furthermore, by applying the model to the dissolution profile, parameters such as the precipitation rate and the potential solubility of the amorphous drug were successfully calculated. In addition, it was shown that the improvement in solubility with supersaturation was able to be evaluated quantitatively using this model. Therefore, this mathematical model would be a useful tool to quantitatively determine the supersaturation concentration of a metastable drug from solid dispersions.

Adsorption of ciprofloxacin and norfloxacin from aqueous solution onto granular activated carbon in fixed bed column

Carbonization of Phoenix dactylifera L stones followed by microwave K2CO3 activation was adopted for preparation of granular activated carbon (KAC). High yield and favorable pore characteristics in terms of surface area and pore volume were reported for KAC as follows: 44%, 852m2/g, and 0.671cm3/g, respectively. The application of KAC as adsorbent for attraction of ciprofloxacin (CIP) and norfloxacin (NOR) was investigated using fixed bed systems. The effect of flow rate (0.5–1.5ml/min), bed height (15–25cm), and initial drug concentration (75–225mg/l) on the behavior of breakthrough curves was explained. The fixed bed analysis showed the better correlation of breakthrough data by both Thomas and Yoon-Nelson models. Inlet drug concentration was of greatest effect on breakthrough data compared to other fixed bed variables. Experimental and calculated breakthrough data were obtained for CIP and NOR adsorption on KAC, thus being important for design of fixed bed column.

Adsorptive Removal of Fluoroquinolones from Water by Pectin-Functionalized Magnetic Nanoparticles: Process Optimization Using a Spectrofluorimetric Assay

The efficiency of adsorption of two photosensitive fluoroquinolones; Ciprofloxacin (CIP) and Moxifloxacin (MOX), on the surface of synthesized magnetite/pectin nanoparticles (MPNPs) and magnetite/silica/pectin nanoparticles (MSPNPs) was studied from aqueous solution under varying experimental conditions. A validated spectrofluorimetric assay was developed for monitoring of CIP and MOX intact drugs and their photodegraded molecules concentrations. To optimize the working conditions which influence the drugs sorption, a 24 full factorial experimental design was implemented. The maximum percentage of removal was attained as 89% (type of sorbent = MSPNPs, pH = 7.0, initial drug concentration = 5 mg/L, and contact time = 30 min). The studied factors—pH, NPs loading, initial drug concentration, and contact time—were significant for both types of sorbents. The most significant variable was pH, and the highest CIP and MOX adsorption occurred at pH = 7.0. Equilibrium isotherm data were fitted to Langmuir, Freundli...