Drug Concentration In Solution Research Articles

Brain targeting efficacy of novel drug delivery system in the treatment of Alzheimer's disease.

Alzheimer's disease (AD), a common degenerative disease of the central nervous system in the elderly, has become the third largest health killer after cardiovascular and cerebrovascular diseases and tumors. Based on the fact that Alzheimer's disease is a disease with multiple etiologies and complex pathology, a single target is bound to have a limited curative effect, and the synergy of multiple links and multiple targets is expected to achieve a better curative effect. The aim of this study is to investigate the brain targeting of a drug modified by chitosan, based on the new nanodrug delivery system for treating Alzheimer's disease developed by the research group. Chitosan with good biocompatibility, biosorption, and degradation products that can protect and promote the regeneration of nerve cells was selected to combine with galantamine, a natural representative cholinesterase inhibitor, to develop a new nano drug delivery system for nasal delivery of anti-Alzheimer's disease with a multi-target synergistic effect. Synchronous analysis was conducted on the blood and brain tissue drug concentrations after intravenous and nasal administration of the original drug solution and system solution. The brain targeting index (DTI) is used to evaluate the brain targeting effect of the nano-drug delivery system after intranasal administration. The blood concentration of galantamine original drug solution and galantamine system solution after intravenous injection and nasal show that in the two administration methods of intravenous injection and nasal administration, under the same administration method, the time point of the system reaching the highest blood drug concentration is much higher than that of the original drug. The content of galantamine in plasma samples and tissue samples indicate that after intravenous administration and intranasal administration of the galantamine system, at the same time point, the drug concentration in brain tissue was far greater than that of the original drug of galantamine, and the duration was also longer. The concentration of drugs in brain tissue decreased gradually in the order of olfactory bulb, olfactory tract, brain, and cerebellum. In the brain tissues of the olfactory bulb, olfactory tract, cerebrum, and cerebellum, the drug concentration of the galantamine system after intravenous injection is lower than that after nasal administration. This study concludes that compared with the original drug solution, the nano drug delivery system has significant brain targeting for nasal administration, and intravenous injection also has brain targeting. In the olfactory bulb, olfactory tract, brain, and cerebellum, the brain targeting index at the olfactory bulb is the highest, and the targeting is the best.

A study of hydrophobic domain formation of polymeric drug precipitation inhibitors in aqueous solution

Despite the widespread use of polymers as precipitation inhibitors in supersaturating drug formulations, the current understanding of their mechanisms of action is still incomplete. Specifically, the role of hydrophobic drug interactions with polymers by considering possible supramolecular conformations in aqueous dispersion is an interesting topic. Accordingly, this study investigated the tendency of polymers to create hydrophobic domains, where lipophilic compounds may nest to support drug solubilisation and supersaturation. Fluorescence spectroscopy with the environment-sensitive probe pyrene was compared with atomistic molecular dynamics simulations of the model drug fenofibrate (FENO). Subsequently, kinetic drug supersaturation and thermodynamic solubility experiments were conducted. As a result, the different polymers showed hydrophobic domain formation to a varying degree and the molecular simulations supported interpretation of fluorescence spectroscopy data. Molecular insights were gained into the conformational structure of how the polymers interacted with FENO in solution phase, which apart from nucleation and crystal growth effects, determined drug concentrations in solution. Notable was that even at the lowest polymer concentration of 0.01 %, w/v, there were polymer-specific solubilisation effects of FENO observed and the resulting reduction in apparent drug supersaturation provided relevant knowledge both from a mechanistic and practical perspective.

An Artificial Gut/Absorption Simulator: Understanding the Impact of Absorption on In Vitro Dissolution, Speciation, and Precipitation of Amorphous Solid Dispersions.

Upon dissolution, amorphous solid dispersions (ASDs) of poorly water-soluble compounds can generate supersaturated solutions consisting of bound and free drug species that are in dynamic equilibrium with each other. Only free drug is available for absorption. Drug species bound to bile micelles, polymer excipients, and amorphous and crystalline precipitate can reduce the drug solute's activity to permeate, but they can also serve as reservoirs to replenish free drug in solution lost to absorption. However, with multiple processes of dissolution, absorption, and speciation occurring simultaneously, it may become challenging to understand which processes lead to an increase or decrease in drug solution concentration. Closed, nonsink dissolution testing methods used routinely, in the absence of drug removal, allow only for static equilibrium to exist and obscure the impact of each drug species on absorption. An artificial gut simulator (AGS) introduced recently consists of a hollow fiber-based absorption module and allows mass transfer of the drug from the dissolution media at a physiological rate after tuning the operating parameters. In the present work, ASDs of varying drug loadings were prepared with a BCS-II model compound, ketoconazole (KTZ), and hypromellose acetate succinate (HPMCAS) polymer. Simultaneous dissolution and absorption testing of the ASDs was conducted with the AGS, and simple analytical techniques were utilized to elucidate the impact of bound drug species on absorption. In all cases, a lower amount of crystalline precipitate was formed in the presence of absorption relative to the nonsink dissolution "control". However, formation of HPMCAS-bound drug species and crystalline precipitate significantly reduced KTZ absorption. Moreover, at high drug loading, inclusion of an absorption module was shown to enhance ASD dissolution. The rank ordering of the ASDs with respect to dissolution was significantly different when nonsink dissolution versus AGS was used, and this discrepancy could be mechanistically elucidated by understanding drug dissolution and speciation in the presence of absorption.

Pluronic F-68 Montmorillonite As A Drug Delivery Vehicle For Extended Release Of Venlafaxine Hydrochloride.

Short half-life and low bioavailability of Venlafaxine hydrochloride (VF), an antidepressant drug, necessitates the frequent administration of VF tablets in a day in order to maintain adequate drug concentration in blood plasma. This generates the need for the development of formulations which could prolong the release of VF and reduce the multiple dosages. The present work explores the combination of Montmorillonite (Mt) with Pluronic F-68 (PF-68) (OrganoMT) for oral delivery of VF. The effect of various parameters including pH of aqueous drug solution, contact time and initial drug concentration on drug loading capacity of OrganoMT has been studied. The synthesized OrganoMT-VF complexes were characterized by various suitable techniques. XRD studies indicated that the VF molecules were intercalated within the OrganoMT layers. In vitro release behavior of VF from OrganoMT-VF complexes shows an extended-release pattern for a period of 30 h and reaches upto 70% and 60% compared to pure VF having complete release time of 5.5 h and 3.5 h in simulated gastric and intestinal fluid respectively. Various kinetic models were employed to elucidate the drug release mechanism where the best fitting was obtained with Korsmeyer Peppas model. The results suggest the possibility of designing an oral extended controlled release formulation for VF to minimize its administration frequency thereby increasing the effectiveness of drug. This improves patient compliance by reducing the dose from 4 times in 24 h to once in 24 h.

Supercritical fluid coating of flavonoids on excipients enhances drug release and antioxidant activity

Supercritical anti-solvent fluidized bed (SAS-FB) technology can be applied to reduce particle size, prevent particle aggregation, and improve the dissolution and bioavailability of poorly soluble drugs. In this work, drug-loaded microparticles of three similar structures, the flavonoids luteolin (LUT), naringenin (NGR), and dihydromyricetin (DMY) were prepared using SAS-FB technology, to explore its effect on the coating of flavonoid particles. Operating temperature, pressure, carrier, solvent, and concentration of drug solution were investigated for their effects on the yield and dissolution of flavonoid particles. The results showed that temperature, pressure, carrier, and drug solution concentration have a large effect on yield. Within the study range, low supercritical CO2 density at higher temperature and lower pressure, a larger surface area carrier, and moderate drug solution concentration led to a higher yield. The effect of the solvent on the yield of flavonoids is a result of multiple factors. Scanning electron microscopy (SEM) images showed that the drug-loaded particles prepared from different carriers and solvents have different precipitations pattern on the carrier surface, and their particle sizes were smaller than unprocessed particles and those prepared by the SAS process. Fluorescence microscopy (FM) results showed that the flavonoids were uniformly coated on the carrier. X-ray powder diffraction (XRPD) results showed that the crystalline morphology of SAS-FB particles remained unchanged after the SAS-FB process, although the diffraction peak intensity decreased. The cumulative dissolution of SAS-FB particles was more than four times faster in the first 5 min than that of the unprocessed flavonoids. The antioxidant activity of SAS-FB processed LUT, NGR and DMY was 1.89-3.78 times, 4.92-10.68 times and 0.99-2.57 times higher than that of the untreated flavonoids, respectively. The approach provides a reference for the application of SAS-FB technology in flavonoids.

Influence on the concentration of drug solution in a venous reservoir by the change of flow rate of a blood pump

Influence on the concentration of drug solution in a venous reservoir by the change of flow rate of a blood pump

Study of Interactions Between 3-benzoyl-4-hydroxy-2-methyl-2H-1, 2-benzothiazine and Human DNA by Theoretical, Spectroscopic and Viscometric measurements.

From the last few years mode of interactions between drugs and DNA is an attractive research area as it bridges chemistry, molecular biology and medicinal science. Interactions between small heterocyclic molecules and human DNA is a noteworthy feature in pharmacology for investigation of drugs mechanism and designing of more effective and target specific drugs with fewer side effects. The present research work focuses on the theoretical investigations of 3-benzoyl-4-hydroxy-2-methyl-2H-1, 2-benzothiazine (SASA) by using Gaussian (16W) software to predict optimized geometry, HOMO-LUMO gap, bond length, bond angle, dihedral angle, electronic and vibrational spectra. Possible reaction site observed in SASA was C7, C9 and C18 as these atoms show maximum charge density. Later the interactions of SASA with human DNA was explored spectroscopic investigations and viscometric investigations at physiological buffers of pH of 4.7 (stomach pH) and 7.4 (blood pH) respectively. Maximum absorbance between SASA-DNA complex was observed in buffer solution of pH 3.4 at wavelength of 370nm, whereas at 7.4 has maximim absorbance between. Spectroscopic results reflects the bathochromic and hyperchromic shift succeeding the addition of human DNA. During viscosity measurement, intercalation and electrostatic mode of interaction were detected at low and high concentration of drug in solution respectively. Increase in the value of rate constant was observed with the increase in concentration of drug. Larger values of rate constant were observed at pH 7.4 in comparison to pH 3.5. Rate constant, thermodynamic parameters and viscometric analysis prefers the intake of SASA via blood.

Chronotropic action of immobilized subtilisins during the perfusion of an isolated rat heart

The pharmacological experiments on isolated organs (ex vivo) are the preferred method for assessing the primary pharmacodynamics of the studied drugs, since this method is completely excluded the systemic influence of neurohumoral regulation. In the last decade, a new group of thrombolytic drugs based on immobilized subtilisins has been formed. At the stage of registrational preclinical and clinical studies, their pleiotropic pharmacological effects have not been studied. Meanwhile, there is a reason to consider that their pharmacological activity in the bloodstream is not limited to thrombolytic action, but may be extended to a systemic effect on the cardiovascular system. The aim of the study was to investigate the chronotropic effects of an isolated heart during its perfusion with solutions of immobilized subtilisins at different concentrations. Material and methods. The isolated rat heart model according to Langendorff was used in the study. The experiment included 50 Wistar rats, which were divided into 5 groups: isolated hearts perfused only with Krebs – Henseleit solution (control) or with immobilized subtilisins in 4 concentrations (170, 340, 510 и 1020 U/l). Results and discussion. The immobilized subtilisins have a negative chronotropic effect. The onset of the effect depends on the drug concentration in the solution: the higher concentration, the earlier effect. From 5 to 10 minutes of perfusion, a negative chronotropic effect is observed using of immobilized subtilisins at any dose. The duration of its increase is manifested up to 10–20 minutes, depending on the drug concentration in solution. After 20 minutes of perfusion, the achieved negative chronotropic effect remains at a plateau level up to 40 minutes. Conclusion. The immobilized subtilisins have an independent pharmacological effect on heart rate.

Adsorptive removal of antibiotic ofloxacin in aqueous phase using rGO-MoS2 heterostructure

This paper reports the synthesis, characterization and detailed adsorption studies of rGO-MoS2 heterostructure. The heterostructure was explored for the adsorption of ofloxacin from the aqueous phase. Detailed studies were conducted to study the effect of crucial parameters such as pH of drug solution, adsorbent dose, temperature and initial drug concentration on the adsorption capacity. Even with a low surface area of 17.17 m2/g, the adsorbent exhibited maximum removal efficiency of 95% at a dose of 0.35 g/L and an initial drug concentration of 10 mg/L in 240 min. Thermodynamic study revealed the values for ∆H0 and ∆G0 to be − 101.15 and − 7.47 kJ/mol respectively, indicating that the process is spontaneous and exothermic in nature. The heterostructure adsorbent exhibited remarkable reusability and stability up to five cycles. The heterostructure combines excellent adsorption capabilities arising from the two-dimensional structures of rGO and MoS2 with the stronger and more specific interaction with the drug molecules which results in better performance towards the removal of the drug. The excellent performance of the heterostructure indicates that combining 2D materials can be a good strategy for producing highly efficient materials towards the adsorptive removal of pollutants.

Drop-by-drop solvent hot antisolvent interaction method for engineering nanocrystallization of sulfamethoxazole to enhanced water solubility and bioavailability

In this study, we investigated the drop-by-drop solvent hot antisolvent interaction (DBD-SAI) method for the production of sulfamethoxazole (SMZ) nanoparticles. We thoroughly investigated the effect of different experimental parameters. Hydroxypropyl methylcellulose (HPMC), polyacrylic acid (PAA), polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), and sodium dodecyl sulfate (SDS) were used as additives. From particle size and shape analysis, it was confirmed that the obtained nanoparticles of SMZ were less than 220 nm with spherical morphology, and thin circular-shaped flakes (4–5 μm) demonstrated in the presence of the additive PVP. It was observed that particle size increased with the pressure of drug solution and drug concentration and decreased with increased rate of stirring. The formulated samples demonstrated an enhanced solubility, drug-release percentage, and anti-bacterial activity compared with raw SMZ. The solubility increased a minimum of 7 times and a maximum of 18 times compared with those of raw SMZ for nano-SMZ and SMZ-PVA, respectively. The drug-release profile showed that more than 95% of SMZ was released within 1 h. Anti-bacterial activity was evaluated against gram positive bacteria Staphylococcus aureus and gram negative bacteria Escherichia Coli. SMZ-PVA showed nearly doubled anti-bacterial activity compare to raw-SMZ.

Synthesis, characterizations and kinetic study of metal organic framework nanocomposite excipient used as extended release delivery vehicle for an antibiotic drug

The present work was to investigate the zinc-based metal-organic frameworks (MOF-5) as oral drug delivery vehicle for the extended in-vitro release of antibiotic drug metronidazole (MTD). The MOF-5 was synthesized by the solvothermal process and characterized by a series of analytical techniques such as PXRD, FTIR, FESEM, HRTEM, TGA and BET. The TEM analysis of the drug loaded nanocomposite (MTD@MOF5) shows the particles size less than in the range of 40–90 nm in dimension. Adsorption of metronidazole on MOF-5 was then estimated as a function of pH in the aqueous drug solution, contact time and initial drug concentration. High loading of metronidazole was found to be 539.33 mg/g of MOF-5 at pH 2. The kinetic results follow the pseudo-second-order model and the isotherm was best described by Freundlich adsorption and Temkin isotherm model respectively. The comparison of in-vitro release behavior of metronidazole drug and the present nanocomposite were explored in the simulated gastric (PBS, pH 1.2) and simulated intestinal fluids (PBS, pH 7.4). The drug shows the excellent releasing power from the MTD@MOF5 nanocomposite as compare to the pure metronidazole drug in terms of availability for the extended time periods.

Preparation of Balangu (Lallemantia royleana) seed mucilage aerogels loaded with paracetamol: Evaluation of drug loading via response surface methodology

In this work, paracetamol (PCM) loading into Balangu seed mucilage (BSM) aerogels was investigated using the combination of supercritical drying and gas antisolvent (GAS) precipitation method. Response surface methodology (RSM) was implemented for the modeling and optimization of drug loading into the aerogel matrix. The temperature (40–60 °C), pressure (8–24 MPa) and drug solution concentration (0.2–0.6 M) were considered as the range of operating variables. The prepared aerogels were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy and N2 adsorption-desorption analysis. The optimal operating conditions were determined to be the pressure of 8 MPa, the temperature of 40 °C and the drug solution concentration of 0.2 M in which the maximum drug loading (DL) of 33% was achieved. The RSM verified that R2 and modified R2 of the model were 98.53% and 97.25%, respectively.

Ultrasound assisted crystallization of a new cardioactive prototype using ionic liquid as solvent

This work deals with the antisolvent crystallization of LASSBio-294 (3,4-methylenedioxybenzoyl-2-thienylhydrazon) assisted by ultrasound. An ionic liquid (IL), 1-ethyl-3-methylimidazolium methyl phosphonate [emim][CH3O(H)PO2] was used as solvent and water as antisolvent. The influence of the following parameters on crystals properties (size distribution, morphology, residual solvent and in vitro dissolution) were studied with two mixing mode (quick and dropwise) of solution with antisolvent. The impact of washing and drying process was also evaluated. Comparative studies of conventional crystallization conditions (without ultrasound) were also performed. The effect of ultrasound on LASSBio-294 recrystallized properties was influenced by the add mode, water/IL ratio and drug solution concentration. As example, US promoted the formation of small crystals with high residual IL under the following conditions: quick addition, high drug solution concentration and high water/IL ratio. However, despite the decrease of elementary particle size, ultrasound did not avoid crystals agglomeration. The drug dissolution rate was affected by the physical structure of agglomerates. When employed as drying process of washed crystals, spray drying reduced this agglomeration and improved the dissolution of LASSBio-294 crystals.

Solubility of trans-resveratrol in Transcutol HP + water mixtures at different temperatures and its application to fabrication of nanosuspensions

The solubility of trans-resveratrol in the solvent mixture of Transcutol HP + water was determined experimentally by using the solid-liquid equilibrium method within the temperatures range 288.15–313.15 K. The mole fraction solubility of trans-resveratrol increased with increasing temperature of the mixture or fraction of Transcutol HP. The highest mole fraction solubility (1.61 × 10−1) of trans-resveratrol was observed in pure Transcutol HP at 313.15 K, whereas the lowest value (1.29 × 10−6) was found in pure water at 288.15 K. The measured solubility data were correlated with van't Hoff, Jouyban-Acree, and Jouyban-Acree-van't Hoff computational models. Thermodynamic analysis suggested an endothermic and spontaneous dissolution behavior of trans-resveratrol in the studied solvents. When the formulation composed of hydroxypropyl methylcellulose/polyvinylpyrrolidone K12/sodium lauryl sulfate (1.0%/0.5%/0.1%, w/w) was used, the formulation prepared at 0.1 mass fraction resulted in an average particle size of 234.8 to 754.6 nm and the smallest particle size was observed for the formulation prepared using concentration of drug solution with 0.025. It was confirmed that the nanosuspension was produced at the ratio determined to be suitable on the basis of the measured solubility data. Therefore, the experimental solubilities and computational model can be useful for formulation studies using trans-resveratrol.

SPECTROSCOPIC EVALUATION OF ACTIVATED CHARCOAL AS A POISON ANTIDOTE FOR GLICLAZIDE DRUG

Objective: The aim of the present study is to evaluate the ability of activated charcoal in adsorbing overdosage of gliclazide drug, and to study the effects of pH, concentration and time on this process.Methods: To evaluate the effect of pH, concentration and time; 50 ml of the drug solution (100 mg/L) were allowed to stand with the activated charcoal for 1 h at pH of 1.5, 4, 7, and 9 for pH study. 50 ml of the drug solution concentrations of 25, 50, 75, and 100 (mg/L) were allowed to stand with 1 g activated charcoal for 1 h for concentration study. 50 mg of the drug solution (100 mg/L) were allowed to stand with the activated charcoal for 15, 30, 45, and 60 min for time study. The concentrations of the adsorbed drug were determined spectrophotometrically.Results: The adsorption of the gliclazide drug on activated charcoal was found to be pH, concentration, and time-dependent. The amounts of the drug adsorbed were 3, 0.75, 0.6, and 0.5 mg/g for pHs 1.5, 4, 7, and 9, respectively, for pH study. For concentration study, the amounts adsorbed were 0.15, 0.22, 0.33, and 0.58 mg/g for concentrations 25, 50, 75, and 100 mg/L, respectively. For time study, the amounts were 0.3, 0.4, 0.51, and 0.65 mg/g for reaction times 15, 30, 45, and 60 min, respectively.Conclusion: The best adsorption circumstances of gliclazide drug on activated charcoal that were found; acidic pH, a high concentration of the drug and longtime of contact.

Ultrasound‐Assisted Anti‐Solvent Crystallization of Telmisartan Using Dimethyl Sulfoxide as Organic Solvent

AbstractIn recent years, ultrasound assisted anti‐solvent crystallization has emerged as an excellent approach to reduce the particle size of poorly water‐soluble drugs, thereby achieving improvement in the solubility and bioavailability. In the present study, this concept is employed for telmisartan by studying various critical parameters like the effect of sonication time, sonication amplitude, drug solution concentration, solvent to anti‐solvent ratio, injection rate and crystallization temperature. The particle size of the commercial telmisartan is reduced from 10 µm to 200 nm by anti‐solvent crystallization method by applying 60% ultrasound amplitude for 15 min with 10 mg mL−1 drug concentration, 1:3 of solvent to anti‐solvent ratio, and 10 mL min−1 of injection rate at 30 °C. Physicochemical characteristics; morphology, crystalline structure, the presence of other chemical compounds, enthalpy change, and the melting point of a recovered drug are analyzed using various analytical tools. It is possible to achieve nanoparticles of telmisartan by symbiotic effect of sonication with anti‐solvent crystallization.

Understanding the generation and maintenance of supersaturation during the dissolution of amorphous solid dispersions using modulated DSC and 1H NMR

In this study, the dissolution behaviour of dipyridamole (DPM) and cinnarizine (CNZ) spray-dried amorphous solid dispersions (ASDs) using polyvinyl pyrrolidone (PVP) and polyacrylic acid (PAA) as a carrier matrix were evaluated and compared. The drug concentrations achieved from the dissolution of PVP and PAA solid dispersions were significantly greater than the equilibrium solubility of crystalline DPM and CNZ in phosphate buffer pH 6.8 (PBS 6.8). The maximum drug concentration achieved by dissolution of PVP and PAA solid dispersions did not exceed the theoretically calculated apparent solubility of amorphous DPM and CNZ. However, the degree of supersaturation of DPM and CNZ increased considerably as the polymer weight fraction within the solid dispersion increased. In addition, the supersaturation profile of DPM and CNZ were studied in the presence and absence of the polymers. PAA was found to maintain a higher level of supersaturation compared to PVP. The enhanced drug solution concentration following dissolution of ASDs can be attributed to the reduced crystal growth rates of DPM and CNZ at an equivalent supersaturation. We have also shown that, for drugs having high crystallization tendency and weak drug-polymer interaction, the feasible way to increase dissolution might be increase the polymer weight fraction in the ASD. Solution 1H NMR spectra were used to understand dissolution mechanism and to identify drug-polymer interaction. The change in electron densities of proton attached to different groups in DPM and CNZ suggested drug-polymer interaction in solution. The relative intensities of peak shift and nature of interaction between drug and polymer in different systems are different. These different effects suggest that DPM and CNZ interacts in a different way with PVP and PAA in solution which goes some way towards explaining the different polymeric effect, particularly in terms of inhibition of drug recrystallization and dissolution of DPM and CNZ ASDs. These results established that the different drug/polymer interactions in the solid state and in solution give rise to the variation in dissolution profile observed for different systems.

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.

Furazolidone Immobilized in a Hydrogel Based on Crosslinked Carboxymethyl Cellulose

The paper deals with the obtainment of a polymer-drug system with controlled release of the biological active principle, based on furazolidone included in a hydrogel obtained by crosslinking of carboxymethylcellulose with epichlorohydrine. The influence of temperature and duration of crosslinking reaction on the<br />crosslinking degree of carboxymethylcellulose (indirectly appreciated by its swelling capacity in polar liquids as water and dimethylformamide/water mixtures) is studied. Kinetic data concerning the inclusion of furazolidone from solution, in the hydrogel of crosslinked carboxymethylcellulose, as well as the release of the drug from the obtained polymer-drug system, are performed. The obtained results evidence that the inclusion<br />rate as well as the amount of furazolidone diffused into the support depend on the dymethylformamide/water ratio utilized as solvent, and on the drug concentration in solution. The product obtained through the insertion of furazolidone from a DMF/water mixture = 5/1 (with a content of 8.9 mg drug/hydrogel) was studied as to the kinetics of the active principle’s release, in vitro, by using as an eluent a buffer solution, which simulates the gastric fluid (pH = 2.4). The experimental results prove the obtention of a polymerdrug system with controlled release of the biologically active principle, conform to a zero order kinetic, in the time interval ranging between 3–12 hours.

Origin of Nanodroplet Formation Upon Dissolution of an Amorphous Solid Dispersion: A Mechanistic Isotope Scrambling Study

It has been observed that certain amorphous solid dispersions (ASDs), upon dissolution, generate drug-rich amorphous nanodroplets. These nanodroplets, present as a dispersed phase, can potentially enhance oral bioavailability of poorly soluble drugs by serving as a drug reservoir that efficiently feeds the continuous aqueous solution phase following absorption of drug. The purpose of this study is to probe the formation mechanism of the nanodroplets. The model system studied was nifedipine (NFD) formulated as an ASD with hydroxypropyl methylcellulose E5 Premium LV or polyvinylpyrrolidone/vinyl acetate. Dissolution of ASDs prepared with proteated nifedipine (H-NFD) was carried out in a medium saturated with deuterated nifedipine (D-NFD) at the amorphous solubility. Upon dissolution, the H/D composition of NFD aqueous solution was determined using nuclear magnetic resonance spectroscopy. The results suggested that isotopic scrambling (equilibrium in the distribution of deuterated and proteated form of the drug) had occurred. Thus, as the H-NFD was brought into the aqueous solution via ASD dissolution, the drug concentration in solution exceeded the amorphous solubility. Subsequent precipitation of the drug, a process which does not differentiate H-NFD from D-NFD, generated NFD nanodroplets and resulted in redistribution of the isotopes. Thus, nanodroplets of NFD are formed due to dissolution of these homogenous ASDs followed by precipitation of the drug from aqueous solutions.