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Decomposition Kinetics of Levofloxacin: Drug-Excipient Interaction


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The present study is focused on the thermal decomposition of Levofloxacin in the absence and presence of different excipients (sodium starch glycolate, magnesium stearate, microcrystalline cellulose and lactose using Thermogravimetry (TG). Fourier Transform Infra Red Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) were used to study the possible drug – excipient interaction. It has been shown that the interaction of the first three excipients (sodium starch glycolate, magnesium stearate, and microcrystalline cellulose) with Levofloxacin is physical in nature. Lactose was shown to decrease the degradation temperature to a maximum extent. This indicates a strong chemical interaction between the drug and lactose. The activation energies in the former case were found almost similar but deviated considerably in the latter case.
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Z. Phys. Chem. 2020; 234(1): 117–128
Jan Nisar*, Mudassir Iqbal, Munawar Iqbal, Afzal Shah,
Mohammad Salim Akhter, Sirajuddin, Rafaqat Ali Khan,
Israr Uddin, Luqman Ali Shah and Muhammad Sufaid Khan
Decomposition Kinetics of Levofloxacin:
Drug-Excipient Interaction
Received July 31, 2018; accepted February 21, 2019
Abstract: The present study is focused on the thermal decomposition of
Levofloxacin in the absence and presence of different excipients (sodium starch
glycolate, magnesium stearate, microcrystalline cellulose and lactose using
Thermogravimetry (TG). Fourier Transform Infra Red Spectroscopy (FTIR) and
Differential Scanning Calorimetry (DSC) were used to study the possible drug –
excipient interaction. It has been shown that the interaction of the first three
excipients (sodium starch glycolate, magnesium stearate, and microcrystalline
cellulose) with Levofloxacin is physical in nature. Lactose was shown to decrease
the degradation temperature to a maximum extent. This indicates a strong chemi-
cal interaction between the drug and lactose. The activation energies in the former
case were found almost similar but deviated considerably in the latter case.
Keywords: drug-excipient interaction; excipients; kinetic analysis; levofloxacin;
thermal decomposition.
*Corresponding author: Jan Nisar, National Centre of Excellence in Physical Chemistry,
University of Peshawar, Peshawar 25120, Pakistan, e-mail:
Mudassir Iqbal, Luqman Ali Shah and Muhammad Sufaid Khan: National Centre of Excellence
in Physical Chemistry, University of Peshawar, Peshawar 25120, Pakistan
Munawar Iqbal: Department of Chemistry, The University of Lahore, Lahore, Pakistan
Afzal Shah: Department of Chemistry, College of Science, University of Bahrain, Sakhir 32038,
Bahrain; and Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan
Mohammad Salim Akhter: Department of Chemistry, College of Science, University of Bahrain,
Sakhir 32038, Bahrain
Sirajuddin: National Centre of Excellence in Analytical Chemistry, University of Sind, Jamshoro,
Rafaqat Ali Khan: Department of Chemistry, COMSATS Institute of Information Technology,
Abbottabad 22060, Pakistan
Israr Uddin: Department of Otorhinolaryngology, Khyber Medical College Peshawar, Peshawar,
118 |J. Nisar et al.
Levofloxacin is an antibiotic used to treat bacterial infection [1–3]. In order to
make it appropriate for administration for treatment of a specific infection it is
blended with a suitable excipient which is normally an inert substance. Excipient
not only improves the drug manufacturing properties and facilitates its admin-
istration but also helps in stabilizing the drug against environmental degrada-
tion [4, 5]. Excipients are always considered to be inert, however, some recent
reports revealed toxicity issues of some common excipients especially in pae-
diatric formulations [6, 7]. Any adverse interaction between drug and excipient
affects the chemical nature of drug and ultimately disturbs the efficiency of drug
against the disease [8–10]. Identification of such reactions and finding out suit-
able safety information for the same would ensure wellbeing of the patients. Var-
ious research groups are involved worldwide for improving drug delivery system.
Saleem et al. [11] used microemulsion formulation for the preparation of nanopar-
ticles of levofloxacin and the fluorescence results supported controlled release of
drug. Baratam and Vijayaratna [12] formulated matrix tablets using hydroxypropyl
methylcellulose with sodium bicarbonate as gas generating agent for sustained
drug delivery of levofloxacin hemihydrate. Asha et al. [13] developed a novel type
of Levofloxacin tablets formulation which was observed to dissolve more swiftly
as compared to standard dosage form. Most recently Chavada et al. [14] employed
an absorption-factor spectrophotometric method for simultaneously determin-
ing azithromycin and levofloxacin in their binary mixtures and the pharmaceu-
tical formulations were observed with no interfering from excipients. Nguyen
et al. [15] reported a simple extractive spectrophotometric method for the deter-
mination of fluoroquinolones in some pharmaceutical products and the proposed
method was found suitable for quantification of fluoroquinolones in pharmaceu-
tical formulations. Mullapudi and Dheram [16] reported an ultraviolet photolysis
decomposition method for the determination of fluoride in fluorine containing
pharmaceuticals and the proposed method was found suitable for routine anal-
ysis of fluoride in organofluorine-containing drugs. Moreover, numerous authors
reported levofloxacin interaction with excipients at ambient temperature taking
into account pH of the blood, UV/Vis light interaction and role of the solvent
[17–23]. El-Megharbel et al. [24] reported synthesis of in-situ copper(II) complexes
of some quinolone in binary solvent and observed that the burst release along
with decreased longitudinal relaxivity can be achieved under acidic environment.
However, to the best of our knowledge Sadeek and El-Shwiniy [25] were the first
to study the decomposition kinetics of levofloxacin metal complexes using Coats–
Redfern and Horowitz–Metzger methods, and the thermodynamic data revealed
Decomposition Kinetics of Levofloxacin |119
thermal stability of all the complexes, therefore, further kinetics investigation is
required for the interaction of levofloxacin with the excipients.
The most important aim of kinetic studies of chemical reaction is to determine
the kinetic parameters [26–29]. These parameters help in predicting the stabil-
ity of different chemical species. The kinetics parameters for a solid substance
are calculated by heating it at isothermal and non-isothermal conditions. Under
isothermal condition kinetic parameters are determined by using the well known
Arrhenius equation, while in case of non-isothermal method, the kinetic parame-
ters are determined by Ozawa Flynn Wall and various other methods. Ozawa Flynn
Wall method was derived from the linear estimation based on the integral calculus
from Arrhenius equation [30–34].
It is interesting to study the degradation of drug at marketing temperatures.
Moreover, the accelerated processes are used for the data collection at elevated
temperatures. Chemical reaction increases at higher temperature. At higher tem-
perature enough energy is provided to break the chemical bond and decompo-
sition starts at that temperature [35, 36]. Therefore, the aim of this work is to
study the kinetics of thermal degradation of levofloxacin in presence of different
excipients using thermogravimetry. FTIR spectra and DSC were also used to study
the possible drug – excipient interaction. The study will help in determination of
compatibility behavior of the drug with different excipients.
2.1 Materials
Levofloxacin has chemical formula C18H20FN3O4·1/2H2O and molecular weight
370.38 g/mol. The drug was purchased from Zhejiang Jingxin Pharmaceutical
China. The excipients microcrystalline cellulose, sodium starch glycolate, lactose
and magnesium stearate were purchased from Allied chemical Karachi.
2.2 Methods
2.2.1 Preparation of the binary mixture
The levofloxacin and all the four excipients were grinded separately in a mortar
till fine powder is formed and then they were mechanically mixed in the ratio of
1:1 (w/w) for further analysis.
120 |J. Nisar et al.
2.2.2 Thermogravimetrical analysis
All the pyrolysis experiments were performed in nitrogen atmosphere
(20 mL/min) in the temperature range 30–600 °C at heating rates of 7.5, 10,
12.5 and 15 °C/min using TG/DTA (Perkin Elmer, USA). The thermograms thus
recorded were interpreted for kinetics study using Ozawa Flynn Wall method.
2.2.3 Dierential scanning calorimetry
The experiments were performed on a Mettler Toledo (Thermo) under nitrogen
atmosphere (20 mL/min). For standard DSC experiments, sample between 5 and
10 mg was heated in the temperature range 25–500 °C at 10 °C/min. Prior to
experiment the equipment was calibrated and the experiments were carried out
in absence and presence of excipients.
2.2.4 Fourier transform infra red spectroscopy
For FTIR analysis, Schimadzue, IR Prestige-21 and FTIR-8400 were used. The drug
alone and with excipients was mixed with IR grade KBr and grinded well using
pestle and mortar. The samples were then scanned in the region 4000–400 cm1.
3Results and discussion
3.1 Kinetic study and thermal behavior of levofloxacin
The weight loss curves (TG) and derivative of weight loss (DTG) of pure lev-
ofloxacin in the absence of excipient at a heating rate of 10 °C/min registered
during the performed pyrolysis are shown in Figure 1. As expected, due to its uni-
form structure, the drug degradation appears to be a single step process (single
degradation peak) with water evaporation at 70 °C while the DTG graph shows the
maximum degradation temperature at 376 °C. The TGA curve indicates that lev-
ofloxacin is thermally stable up to 255 °C and successive mass loss occurs between
255 and 600 °C.
Figure 2a–e exposes TG curves obtained at heating rates 7.5, 10, 12.5 and
15 °C min1for pure levofloxacin and with excepients. It is evident from the
curves that when the heating rate is low, equilibrium is accomplished rapidly
with rise in temperature. However, when the heating rate is high, equilibrium is
delayed which causes shifting of the curve to high temperature [37, 38].
Decomposition Kinetics of Levofloxacin |121
Fig. 1: TGA/DTG curves of pure Levofloxacin in dynamic nitrogen atmosphere (20 mL min1)
and heating rate 10 °C min1.
The activation energy for dynamic study of drug was calculated using Ozawa
Flynn Wall equation [39–41].
Rg(α)5.331 1.052 E
RT (1)
The plot of ln βversus 1/T depicted in Figure 3 was used for calculation of
activation energy. The plots exhibit quite good correlation. The activation energy
was determined as 118.05 kJ/mol for the pure levofloxacin thermal decomposition.
Table 1 shows the activation energies of Levofloxacin alone and with the excipi-
ents using Ozawa’s equation. The table shows that no significant difference in
activation energy is observed for the pure drug using non-isothermal method and
these values are relatively close to each other except lactose. This shows that the
degradation for these entire binary mixture take place in the same temperature
range. The small difference in activation energies in the presence of excipients
shows stability and suitability of the drug for formulation. The small activation
energy determined for the combination of the drug with lactose shows the strong
chemical interaction of the drug with excipient making the drug non-compatible
for solid formulation with this specific excipient.
3.2 Fourier transform infra red spectroscopy
FTIR is an easy, fast and accurate method for assessing drug–excipient
compatibility [42]. The IR analysis of levofloxacin, levofloxacin-sodium starch
122 |J. Nisar et al.
Fig. 2: (a) TG curves of pure Levofloxacin obtained at heating rates 7.5, 10, 12.5 and
15 °C min1. (b) TG curves of the mixture of Levofloxacin with Sodium starch glycolate
obtained at heating rates 7.5, 10, 12.5 and 15 °C min1. (c) TG curves of the mixture of Lev-
ofloxacin with Magnesium stearate obtained at heating rates 7.5, 10, 12.5 and 15 °C min1.
(d) TG curves of the mixture of Levofloxacin and Microcrystalline cellulose obtained at heating
rates 7.5, 10, 12.5 and 15 °C min1and (e) TG curves of the mixture of Levofloxacin and Lactose
obtained at heating rates 7.5, 10, 12.5 and 15 °C min1.
glycolate, levofloxacin-magnesium stearate, levofloxacin-microcrystalline cel-
lulose and levofloxacin-lactose were performed and the spectra obtained are
presented in Figure 4a and b. The levofloxacin FTIR characteristic absorption
Decomposition Kinetics of Levofloxacin |123
Fig. 3: Ozawa Flynn Wall plots at various conversions for the degradation of levofloxacin.
Tab. 1: Activation energy (Ea) values obtained for Levofloxacin in absence and presence of
various excipients by non-isothermal study using Ozawa-Flynn-Wall method.
Sample Activation Energy (kJ mol1)
Levofloxacin 118.05
Levofloxacin/magnesium stearate 94.11
drug/sodium starch glycolate 94.14
Levofloxacin/microcrystalline cellulose 95.77
Levofloxacin/lactose 39.93
peaks were obtained for the –OH group of the –COOH moiety at around
3261.4 cm1and –CO peak near 1725.1 cm1. The aromatic C–H peaks are
also observed in the range 2900–3000 cm1[43]. The main functional bands
of the above mixtures were appeared at different regions. The C–N stretch-
ing at 1236 cm1, C–H aromatic stretching at 1473 cm1, the 1630 and 1600
pair absorption bands may be related to the carbonyl and C=C moiety inside
the levofloxacin, O–H absorption band at 1630 cm1, stretching of CH2at
2929 cm1were observed for all mixtures of the drug and excipients. In
case of lactose an additional new band due to O–H stretching at 3642 cm1
can be seen in Figure 4b. This shows chemical interaction of levoflaxcin
and lactose. This chemical interaction between levofloxacin and excipient
makes lactose as undesirable for the formulation of solid dosage as only
124 |J. Nisar et al.
Fig. 4: (a and b) FTIR spectra of levofloxacin and 1:1 physical mixtures of drug/sodium starch
glycolate, drug/magnesium stearate, drug/microcrystalline cellulose and drug/lactose.
physical interaction is desired, while chemical interaction completely changes
the pharmo kinetics of the drug.
3.3 Dierential Scanning Calorimetry
Figure 5 exposes DSC curves of drug, excipient and drug–excipient mixtures.
The DSC curve for pure levofloxacin exhibited a small endothermic peak at
around 95 °C due to the dehydration of the levofloxacin. Two sharp endothermic
peaks around 190–200 °C are also observed corresponding to its melting point
[44]. These second and third events were reported as the melting of α,βand γ
Decomposition Kinetics of Levofloxacin |125
Fig. 5: DSC curves of Levofloxacin and Excipients alone and Levofloxacin with excipients;
A–Levofloxacin, B–Sodium starch glycolate, C–Magnesium stearate, D–Lactose, E–
Microcrystalline cellulose, F–Levo +Sodium starch glycolate, G–Levo +Magnesium stearate,
H–Levo +Lactose, I–Levo +Microcrystalline cellulose.
levofloxacin polymorphs [45]. Additionally, an exothermic event was observed
due to crystallization of αor βforms from the melted γform [46]. These observa-
tions were in agreement with the documented DSC thermogram for levofloxacin
in literature under the same heating rate 10 °C/min [47, 48]. The endother-
mic peak at around 95 °C peak was observed to disappear for the mixtures
of levofloxacin-magnesium stearate and levofloxacin-microcrystallinecellulose.
This shows that the metal cations present in magnesium stearate in the form of
126 |J. Nisar et al.
magnesium bind themselves to levofloxacin resulting into disappearing of the
endothermic peak. Moreover, microcrystalline cellulose as chelating agent also
exhibits the same property. The results show one exothermic peak at 120–130 °C.
Lactose showed two endothermic peaks around 50 and 260 °C, respectively. The
two transitions in lactose correspond to water loss and lactose melting, respec-
tively. So, the new endothermic peaks appeared around 125 °C and the second
at 165 °C indicate the presence of lactose in the mixture [49], and the lower
activation energy observed for the combination of the drug with lactose is indica-
tive of the fact that some chemical interaction may exist between the drug and
In the present work the activation energies under non-isothermal condition
were determined for the thermal decomposition of levofloxacin and the acti-
vation energy was determined as 118.05 kJ/mol. The stability and compatibil-
ity were studied by using TG/DTG, DSC and FTIR techniques. The compatibility
of levofloxacin with sodium starch glycolate, magnesium stearate, microcrys-
talline cellulose and lactose were investigated and it was observed that the first
three excipients showed good compatibilitywith levofloxacin while lactose exhib-
ited incompatibility due to chemical interaction with the drug. From the results
it can be concluded that a physical interaction exists between the drug and
sodium starch glycolate, magnesium stearate, microcrystalline cellulose, where
as a chemical interaction is evident between the drug and lactose.
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... Currently, the most commonly used resin is primarily petroleumbased and their frameworks are primarily based on aromatic alkanes such as styrene and divinylbenzene. These aromatic alkanes are not contained in the resin and migrate to various substances during use, causing secondary pollution; concerns about the use of fossil fuels have made the development and use of naturally absorbed materials more and more common [4][5][6]. Chen, fuqiang, et al., tried their best to combine the neutralization method and ion exchange resin methods attempted their advantages and eliminate their disadvantages [7]. The resin component plays an important role in the mechanical properties of the material [8][9][10]. ...
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We have studied the interaction of the antibacterial drug levofloxacin with lipid bilayers of various compositions: 100% DPPC and with the addition of 20% cardiolipin. For DPPC liposomes, levofloxacin was found to penetrate into the subpolar region at the lipid-water interface. The role of the anionic lipid in the interaction of an active molecule with a bilayer has been established: levofloxacin enters the microenvironment of the phosphate group, displacing water, and does not penetrate into the hydrophobic part of the bilayer. For the first time, the study of the microenvironment of levofloxacin in the liposome by IR and CD spectroscopy was carried out. Such an approach based on a combination of several spectral methods opens up new prospects for the creation of new medicinal properties and the possibility of predicting the nature of the interaction of active molecules with biomembranes in order to predict their efficacy and potential side effects.
Vildagliptin (VID) is a dipeptidyl peptidase-4 (DPP-4) inhibitor used in controlling blood glucose level in type 2 diabetes. Vildagliptin improves beta cells function and is also suggested to effectively control the inflammation. The possible ocular anti-inflammatory property of vildagliptin has been explored using topically applied plasticized ocular film formulation. Film formulation was prepared by solvent cast and evaporation method using triethanolamine (TEA), dimethyl sulphoxide (DMSO), and polyethylene glycol 400 (PEG 400) as the plasticizer in HPMC hydrogel matrix base. Anti-inflammatory study was carried out in the carrageenan induced ocular rabbit model. Analytical methods confirmed that the drug was present almost in completely amorphized form in the film formulation. Level of hydration, swelling and erosion rate of the film played the controlling factor in the process of drug release, ocular residence and permeation. Maximum swelling rate of 363 h ⁻¹ has been shown by VHT compared to other formulation of VHD and VHP (174 and 242 h ⁻¹ respectively). Film containing DMSO exhibited highest in vitro release as well as ex vivo ocular permeation. Film formulation has shown a fast recovery of ocular inflammation in contrast to the untreated eye after inducing inflammation. Plasticized vildagliptin hydrogel film formulation could be utilized in the management and control of ocular inflammation particularly with diabetic retinopathy after proper clinical studies in higher animal and human individuals.
The docking simulation of benzamide derivatives as ligands and protein targets (DNA–gyrase) was performed and Sec14p binding mode interaction was predicted based on binding free energy analysis. Software Molegro Virtual Docking (MVD) was used to visualize the ligand–protein binding interactions. The results indicated the prevalence of steric or hydrophobic interactions among all the benzamide ligands besides hydrogen bonding or electrostatic interactions. The compounds B2, B4 against DNA gyrase, and compounds B3, B5 against Sec14p showed an uncompetitive pattern of inhibition as compared with the reference molecule. While compounds B1, B5 exhibited the best MolDock scores, i.e., −109.736 and −114.391 kcal/mol respectively for DNA gyrase, also compounds B1 and B2 against Sec14p displayed −100.105 and −119.451 kcal/mol sequentially. It was evident from the comparison of MolDock score for both the bacterial and fungal protein receptors that all the ligands were found to be more potent against DNA gyrase than Sec14p. However, only compound B2 with MolDock score −119.451 kcal/mol showed exceptional activity against Sec14p and was predicted to have potency as a lead compound to find a new anti-fungal therapeutic agent. Docking studies further highlighted the unique interactions such as tail-end hydrophobic rings of benzamide inhibitors with catalytically important amino acid residues, allowing flexibility in binding to both the receptors different from other inhibitors. These findings showed us that B1, B2 against Staphylococcus aureus and B5 against Saccharomyces cerevisiae could be leading compounds to discover new multidrug-resistant strains.
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The chitosan/polyvinyl alcohol/halloysite nanoclay (CS/PVA/HNC) loaded with cephradine drug electrospun nanofibers (NFs) were fabricated and characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA) techniques. FTIR analysis confirmed the hydrogen bonding between the polymer chain and the developed siloxane linkages. SEM analysis revealed the formation of uniform NFs having beads free and smooth surface with an average diameter in 50–200 nm range. The thermal stability of the NFs was increased by increasing the HNC concentration. The antimicrobial activity was examined against Escherichia coli and staphylococcus strains and the NFs revealed auspicious antimicrobial potential. The drug release was studied at pH 7.4 (in PBS) at 37 °C. The drug release analysis showed that 90% of the drug was released from NFs in 2 h and 40 min. Hence, the prepared NFs could be used as a potential drug carrier and release in a control manner for biomedical application.
In this research work nanoparticles of Mg (0, 1, 2 and 3%) doped MoS 2 are prepared by Hydrothermal method at 200 °C for 9 h. Scanning Electron Microscope (SEM) for surface morphology, Fourier Transform Infrared Spectroscopy (FTIR) for structural and chemical bonding and UV-visible spectroscopy for optical properties are used. SEM showed that sheet-like structure has changed into stone-like shaped when Mg has doped into MoS 2 . From FTIR, Mo–O, Mo=S, and H–O bond peaks are becoming dim and new chemical bonds S=O, Mo=O, Mg–O, CH and OH are forming with the increase of Mg doping. UV-visible spectroscopy showed that MoS 2 has an indirect bandgap 2.21 eV. Band gap decreased from 1.84 to 1.82 eV when the Mg doping was increased from 1 to 2%, respectively. As Mg concentration was increased i.e. 3% then band gap increased to 1.88 eV. Photocatalytic activity (PCA) of undoped and Mg doped MoS 2 is appraised by degrading rhodamine blue (RhB) and methylene blue (MB) dyes. The results showed that PCA (in presence of visible light) Mg doped MoS 2 is greater than pure MoS 2 which significantly increased the photocatalytic properties.
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The gamma ray induced degradation of moxifloxacin in aqueous media has been evaluated. The drug solutions (50 & 100 mg/L) were irradiated to absorbed doses of 0.3, 0.6, 0.9, 1.2, 1.5, 2, 3 and 4 kGy using Cs-137 gamma radiation source. The parameters such as drug initial concentration, oxidant (H 2 O 2 ) concentration and gamma ray absorbed doses were optimized. The efficiency of Advanced oxidation processes (AOP) was evaluated on the basis of degradation, reduction in chemical oxygen demand (COD) and toxicity reduction of the drug. The maximum degradation of 94.01 and 88.30% was achieved when drug solutions were exposed to gamma irradiation absorbed dose of 4 kGy which enhanced to 100 and 99.06% in the presence of H 2 O 2 (0.5 mL/L) for 50 and 100 mg/L respectively. A significant reduction in COD 72 and 75% for 50 mg/L while 65 and 69% in case of 100 mg/L was noted using gamma and gamma/H 2 O 2 respectively at absorbed dose of 4 kGy. The parameters such as dose constant (k), removal efficiency ( G -value), gamma ray absorbed doses required for 50, 90 and 99% degradation ( D 0.50 , D 0.90 and D 0.99 ) have been calculated. The radiolytic degradation was monitored by UV–Vis spectrophotometer and HPLC, FT-IR studies were performed to investigate the change in functional groups before and after treatment, while GC-MS analysis was carried out to monitor intermediates/degraded end-products. The FT-IR spectra has shown complete destruction of aromatic rings after radiation treatment but a minor peak appeared at 1216 cm ⁻¹ corresponding to CO stretching. The GC-MS study for the drug samples treated with gamma/H 2 O 2 has shown no any significant peak which confirms the complete degradation. The cytotoxicity of treated samples was carried out by hemolytic assay and mutagenicity using Ames test before and after each treatment. The hemolytic test showed 73.92% hemolysis, while gamma/H 2 O 2 treatment reduced the mutagenicity to 74.08 and 65.66% against TA98 and TA100 bacterial strains respectively. The response surface methodology (RSM) was employed to optimize the data. The obtained data elaborate that gamma/H 2 O 2 process is promising approach for the remediation of pharmaceutical waste effluent.
The present work compares the interaction of the antibiotic levofloxacin (LVX) with zwitterionic and anionic liposomes composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DPPG), respectively. By using differential scanning calorimetry (DSC), and with spin labels incorporated into liposomes at two different depths of the bilayers, we investigated the changes induced on the membrane by increasing concentrations of LVX. Further information was obtained using intrinsic LVX fluorescence. Under the conditions used here, all techniques evinced that LVX has little affinity for DPPC zwitterionic membrane. Opposite to that, LVX exhibits a considerable affinity for anionic bilayers, with membrane partition constants Kp = (3.3 ± 0.5) × 10² and (4.5 ± 0.3) × 10², for gel and fluid DPPG membranes, respectively. On binding to DPPG, LVX seems to give rise to the coexistence of LVX -rich and -poor domains on DPPG membranes, as detected by DSC. At the highest LVX concentration used (20 mol%), DSC trace shows an increase in the cooperativity of DPPG gel-fluid transition, also detected by spin labels as an increase in the bilayer packing. Moreover, LVX does not induce pore formation in either DPPG or POPG vesicles. Considering the possible relevance of LVX-membrane interaction for the biological and toxicological action of the antibiotic, the findings discussed here certainly contribute to a better understanding of its action, and the planning of new drugs.
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In this paper, we reported a new, simple, accurate, and precise extractive spectrophotometric method for the determination of fluoroquinolones (FQs) including ciprofloxacin (CFX), levofloxacin (LFX), and ofloxacin (OFX) in pharmaceutical formulations. The proposed method is based on the ion-pair formation complexes between FQs and an anionic dye, bromothymol blue (BTB), in acidic medium. The yellow-colored complexes which were extracted into chloroform were measured at the wavelengths of 420, 415, and 418 nm for CFX, LFX, and OFX, respectively. Some effective conditions such as pH, dye concentration, shaking time, and organic solvents were also systematically studied. Very good limit of detection (LOD) of 0.084 µ g/mL, 0.101 µ g/mL, and 0.105 µ g/mL were found for CFX, LFX, and OFX, respectively. The stoichiometry of the complexes formed between FQs and BTB determined by Job’s method of continuous variation was 1 : 1. No interference was observed from common excipients occurred in pharmaceutical formulations. The proposed method has been successfully applied to determine the FQs in some pharmaceutical products. A good agreement between extractive spectrophotometric method with high-performance liquid chromatography mass spectrometry (HPLC-MS) for the determination of FQs in some real samples demonstrates that the proposed method is suitable to quantify FQs in pharmaceutical formulations.
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A new approach based on a selective charge transfer reaction with alizarin red S is described for the simultaneous determination of azithromycin and levofloxacin in their binary mixtures using an absorption-factor spectrophotometric method. Native absorbance was used for the determination for levofloxacin, while a charge transfer complexation of alizarin red S served as the basis for the quantitation of azithromycin. The reaction of azithromycin with alizarin red S was possible in methanol under neutral conditions within 15 min at 25 ◦C. The conditions were suitably optimized for selective complexation of azithromycin with minimal interference from levofloxacin. The calibration curve was linear over the concentration range of 4.0–20 µg mL⁻¹ for azithromycin and levofloxacin and the correlation coefficients of the regression equations were consistently greater than 0.9970 for both the drugs. The limit of detection was 1.07 µg mL⁻¹ for azithromycin and 0.84 µg mL⁻¹ for levofloxacin. The developed method was highly reproducible with precision (RSD%) values in the range of 0.54%–0.95% for both the drugs. The method was successfully applied for the simultaneous determination of these antibacterial drugs from their synthetic mixtures and pharmaceutical formulations with no interference from excipients.
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Assembly of pyridine-2-aldoxime drug with cucurbit [6]uril (CB[6]) has been investigated by ¹H-NMR and 2D-ROESY NMR, UV-Vis spectroscopy, FT-IR spectroscopy, surface tension and conductivity measurements in aqueous saline environment. The distinct cationic receptor feature and the cavity dimension of the CB[6] emphasize that the macro-cyclic host molecule remain as complex with the nerve stimulus drug molecule. The results obtained from surface tension and specific conductivity measurements suggest 1:1 inclusion complex formation between drug and CB[6]. The stability constant evaluated by UV-Vis spectroscopic approach is 2.21×10⁵ M⁻¹ at 298.15 K, which indicates that the complex is sufficiently stable at physiological temperature.
Interaction of a cardiovascular drug, Furosemide with cetyltrimethylammonium bromide (CTAB) has been studied in aqueous solutions of Dimethylsulfoxide (DMSO) with the help of density, speed of sound and conductivity measurements over a range of temperatures 293.15-313.15 K at interval of 5 K. The interaction parameters viz. apparent molar volume, Vφ and apparent molar isentropic compression, κs,φ have been enumerated from density and speed of sound data. Also, variation in the micellization behavior has been explored by calculating critical micelle concentration, CMC. It has been observed that micellization tendency of the surfactant decreases in the presence of DMSO as compared to pure aqueous system. Moreover, the CMC values shift toward lower concentration with increase in Furosemide content because of increase in hydrophobic hydration which may be to hydrophobicity of drug molecule. The dependence of CMC in mole fraction (Xcmc) values on the temperature has been analyzed in terms of thermodynamics of the system by reporting the standard thermodynamic parameters i.e. standard Gibb's free energy (ΔGmo), $(\Delta G-m^o),$ enthalpy (ΔHmo) $(\Delta H-m^o)$ and entropy (ΔSmo) $(\Delta S-m^o)$ of micellization for CTAB in mixed solvent systems. The entropies of micellization are all positive, and they compensate the enthalpies of the process. Compensation temperature, Tc has also been evaluated from enthalpy-entropy compensation whose values lies in Lumrys range (270-300 K).
Intranasal route is the best method for high absorption and direct delivery to the brain. The interests and importance, of this route, are that the systemic effects of drugs when administered through the nasal route, have expanded over recent decades and it used for therapeutic and recreational purposes. In comparison with the parenteral route of drug administration, intra-nasal administration of drugs offers an interesting alternative for achieving systemic therapeutic effects of drugs. The oral administration of the drug produces low drug bioavailability, and this can be minimized using this nasal route. Moreover, the advantage of this route is that it can bypass the first-pass metabolism. Therefore, it is important to understand the potential and limitations of various nasal drug delivery systems. The aim of this review article is to discuss the various pharmaceutical dosage forms that have the potential to be utilized for local or systemic drug administration. It is assumingly expected that this review will help to understand about this route and also to develop suitable intra-nasal formulations to achieve specific therapeutic objectives. The different types of nasal drug formulations that can be used are nasal drops, nasal sprays, nasal gels, nasal suspensions and emulsion, and nasal powders.
Microemulsions (μEs) are being exploited as a potential route for yielding an extensive range of nanoparticles of different chemical nature, shapes and sizes. Nanodrugs offer new avenues for structuring better “drug delivery systems”. In this study, an oil‐in‐water (o/w) μE formulation comprising N‐butyl acetate/polysorbate 80/ethanol/water was developed for the preparation of nanoparticles of fluoroquinolone antibiotics (FLQ‐NPs). A pseudoternary phase diagram was mapped at constant surfactant/cosurfactant (1:2), revealing improved and high loading of FLQs in an optimum μE formulation. The as‐formulated μE showed high loading of FLQs as; levofloxacin (4.20 wt.%), ciprofloxacin (3.16 wt.%), moxifloxacin (2.53 wt.%), gatifloxacin (1.36 wt.%), ofloxacin (0.70 wt.%). Fourier transform IR analysis indicated good compatibility of each FLQ drug with μE excipients. However, dynamic light scattering showed an increase in the average particle size of the μE on drug loading, indicating the accumulation of FLQ at interface layer of the micelle. Additionally, lyophilized levofloxacin (a selected antibiotic) showed long‐term stability, amorphous morphology and improved dissolution rate, inspected by scanning transmission electron microscopy, X‐ray diffraction and electronic spectroscopy, respectively. Moreover, fluorescence measurements suggested the interfacial vicinity of levofloxacin within the μE domain, which may support controlled release of drug during systemic circulation.
In order to overcome the challenges of the solid unit dosage forms, Fast Dissolving Tablets (FDT) or orally disintegrating tablets (ODT) has emerged as alternative oral dosage forms. These novel types of tablets have the ability to dissolve more rapidly when compared to standard solid dosage forms. The main objective of the present study was to develop Oral dispersible tablet formulation containing 150mg of Levofloxacin for the treatment of a number of infections including infection of Joints and bones, respiratory tract infections, urinary tract infections, skin structural infections and typhoid fever etc. In our study, it was observed that all the values of pre-compression and post-compression studies were within the limits.
Captopril (CAP) was the first commercially available angiotensine-converting enzyme (ACE) inhibitor. In the anti-hypertensive therapy is considered the selected drug has to be therapeutically effective together with reduced toxicity. CAP is an antihypertensive drug currently being administered in tablet form. In order to investigate the possible interactions between CAP and excipients in tablets formulations, differential scanning calorimetry (DSC) and thermogravimetric (TG) analysis completed by X-ray powder diffraction (XRPD) and Fourier transform infrared spectroscopy (FTIR) were used for compatibility studies. A possible drug-excipient interaction was observed with magnesium stearate by DSC technique.
Background: The opening patient statement is an important part of the medical consultation. It is where after the initial solicitation the physician gets information about the patient's current problems and concerns. Previous research shows that 23-28% of patients are allowed to complete their opening statement un-interruptedly in the general practice setting. Interruption results in fewer patient concerns expressed and failure to gather potentially important patient information. Objectives: The objective of the study was to assess the duration of opening statements of patients attending a chronic pain clinic consultation. Study design: Prospective observational study SETTING: Chronic pain clinic. University teaching hospital METHODS: Following written informed consent, data was collected prospectively from 100 adult patients attending a chronic pain clinic consultation at a university hospital. We recorded the time of the opening statement following a standardized opening question by the pain physician. No verbal or non-verbal interruption by the physician was made during the patient's opening statement. Results: Out of 100 adult patients, 37% (n = 37) were male and 63% (n = 63) were female. Mean age (years) was 54.4. The mean opening statement time was 89 s. Limitations: The study is limited by being a single-centered study. Conclusions: The duration of opening statements of patients attending a chronic pain clinic consultation when systematically studied takes a very short amount of time. It is important that all interruptions should be avoided. Our findings should encourage physicians to allow patients to complete their opening statements un-interruptedly in the chronic pain clinic.
The anticancer drug doxorubicin (DOX) is locked in the mesoporous silica nanoparticle by coating Fe