Search

Cellulose acetate butyrate is a biodegradable cellulose ester bioplastic produced from plentiful natural plant-based resources. Solvent-exchange-induced in situ gels are particularly promising for periodontitis therapy, as this dosage form allows for the direct delivery of high concentrations of antimicrobial agents to the localized periodontal pocket. This study developed an in situ gel for periodontitis treatment, incorporating a combination of metronidazole and doxycycline hyclate, with cellulose acetate butyrate serving as the matrix-forming agent. Consequently, assessments were conducted on the physicochemical properties, gel formation, drug permeation, drug release, morphological topography, and antimicrobial activities of the formulation. The formulation demonstrated an increased slope characteristic of Newtonian flow at higher bioplastic concentrations. The adequate polymer concentration facilitated swift phase inversion, resulting in robust, solid-like matrices. The mechanical characteristics of the transformed in situ gel typically exhibit an upward trend as the polymer concentration increased. The utilization of sodium fluorescein and Nile red as fluorescent probes effectively tracked the interfacial solvent–aqueous movement during the phase inversion of in situ gels, confirming that the cellulose acetate butyrate matrix delayed the solvent exchange process. The initial burst release of metronidazole and doxycycline hyclate was minimized, achieving a sustained release profile over 7 days in in situ gels containing 25% and 40% cellulose acetate butyrate, primarily governed by a diffusion-controlled release mechanism. Metronidazole showed higher permeation through the porcine buccal membrane, while doxycycline hyclate exhibited greater tissue accumulation, both influenced by polymer concentration. The more highly concentrated polymeric in situ gel formed a uniformly porous structure. Metronidazole and doxycycline hyclate-loaded in situ gels showed synergistic antibacterial effects against S. aureus and P. gingivalis. Over time, the more highly concentrated polymeric in situ gel showed superior retention of antibacterial efficacy due to its denser cellulose acetate butyrate matrix, which modulated drug release and enhanced synergistic effects, making it a promising injectable treatment for periodontitis, particularly against P. gingivalis. [ABSTRACT FROM AUTHOR]

Copyright of Baghdad Science Journal is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Diabetic foot ulcer pose a significant challenge in healthcare, often leading to prolonged healing processes and complications requiring sophisticated and advanced therapeutic interventions. This study focuses on the formulation and development of Doxycycline hyclate loaded chitosan nanoparticles in cross-linked topical hydrogel patches for targeted management of DFU healing. Various characterization techniques, such as FT-IR, Zeta potential, DSC, XRD, and SEM, were employed to confirm and gain insights into the structural and morphological features of the crosslinked topical hydrogel patches. The evaluation parameters encompassed analyzing sol-gel behavior, swelling dynamics, and in vitro drug release studies at pH values of 5.5, 6.5, and 7.4. Drug permeation and deposition was performed utilizing the Franz diffusion cell method. The topical hydrogel patches showed pH-sensitive behavior, with enhanced drug release, swelling, and permeation observed at pH 7.4. The synthesized nanoparticles exhibited a spherical morphology, varying particle sizes ranging from 92.83 nm to 206.2 nm, and a zeta potential measuring -22.4 mV. The patches were produced by incorporating CNPs as carriers for DCH into a polymeric matrix, which required the optimization of free radical polymerization. The ion gelation method was utilized to prepare the CNPs. The solvent evaporation technique was used for grafting the topical hydrogel patches. Among the seven formulations, topical hydrogel patch F6 exhibited the most favorable characteristics, as evidenced by a substantial drug content of 97.21 ± 0.524%. The F6 formulation excelled over other formulations over 72 hours at pH 7.4. Stability testing of the selected F6 formulation over 6 months under accelerated conditions confirmed its viability. Therefore, this polymeric network represents an innovative technology for accelerating the healing process of diabetic foot ulcers through the use of doxycycline hyclate loaded chitosan nanoparticles cross-linked in topical hydrogel patches. [ABSTRACT FROM AUTHOR]

This work describes a simple and straightforward magnetic solid phase extraction (MSPE) approach based on benzalkonium chloride-modified silica-coated magnetite nanoparticles (Fe3O4@SiO2@BZC). The developed extraction method was employed for extracting doxycycline hyclate (DOX) from water and urine samples after derivatization with procaine benzylpenicillin (PP) as a color reagent. An orange azo dye with a maximum adsorption wavelength (λmax) of 440 nm was produced by the azo-coupling of DOX with the color reagent in the alkaline medium. The analytical conditions were optimized carefully, including the reagent and surfactant volumes, the amount of sorbent, the extraction time, and the pH of the solution. The developed extraction approach achieved pre-concentration and enrichment factors of 47 and 25, respectively. UV–vis spectroscopy was utilized to determine the target analyte after the extraction step. A good linearity (R2 > 0.99) in the concentration range of 0.08–3.00 μg/mL was achieved. Detection and quantification limits of DOX were found to be 0.01 and 0.04 μg/mL, respectively. The suggested method was successfully applied to the extraction and determination of DOX spiked in urine and various water samples, with excellent recoveries of 97.00–98.30% and 98.00–102.00%, respectively. [ABSTRACT FROM AUTHOR]

Arsenic is a widespread environmental contaminant known to accumulate in the brain, leading to cognitive impairment. However, the exact mechanisms by which arsenic causes cognitive deficits remain unclear. The present study aims to discover whether the destruction of the blood-brain barrier (BBB) mediated by matrix metalloproteinases 2 and matrix metalloproteinases 9 (MMP-2 and MMP-9) and subsequent neuronal apoptosis are involved in arsenic-induced cognitive impairment. Ninety male mice were given 0, 25, and 50 mg/L NaAsO2 in drinking water and 30 mg/kg doxycycline hyclate (DOX, an inhibitor of MMPs) gavage for 12 weeks to observe the alterations in learning and memory of mice, the morphology of hippocampal neurons, as well as the BBB permeability and ultrastructure, the localization and expression of tight junction proteins, MMP-2, and MMP-9. Our findings indicated that arsenic exposure induced learning and memory impairment in mice, accompanied by neuronal loss and apoptosis. Furthermore, arsenic exposure increased hematogenous IgG leakage into the brain, disrupted the tight junctions, reduced the expression of Claudin5, Occludin, and ZO1 in the endothelial cells, and increased the expression of MMP-2 and MMP-9 in the endothelial cells and astrocytes. Finally, DOX intervention preserved BBB integrity, alleviated hippocampal neuronal apoptosis, and improved cognitive impairment in mice caused by arsenic exposure. Our research demonstrates that cognitive disfunction in mice induced by arsenic exposure is associated with MMP-2 and MMP-9-mediated BBB destruction and neuronal apoptosis. The current investigation provides new insights into mechanisms of arsenic neurotoxicity and suggests that MMP-2 and MMP-9 may serve as potential therapeutic targets for treating arsenic-induced cognitive dysfunction in the future.

Objectives: The present study focused on the formulation of mucoadhesive bilayer composite films for the treatment of periodontitis and evaluation of their physicochemical properties. Materials and Methods: The solvent casting technique was used to prepare films. The primary layer (D) was prepared with flaxseed and hydroxypropyl methylcellulose composite to sustain the release of doxycycline hyclate. The second layer (S) comprised sodium alginate and polyvinyl alcohol composite for faster release of clove oil. Both layers were combined to generate the bilayer film (B). All formulations were characterized further to obtain an optimized formulation. Results: Attenuated total reflection-Fourier transform infrared radiation results showed intactness of drug and clove oil in the presence of excipients. The pH of the films was compatible with the periodontal cavity and the thickness was suitable for inserting into the cavity. The immediate release layer showed faster disintegration and swelling. The content of clove oil was above 80%. The rate of swelling of the primary layer was slow and drug content complied with the United States Pharmacopoeia. Scanning electron microscope analysis revealed intact, non-porous and smooth films. Films exhibited better mechanical strength and bioadhesiveness. Clove oil was released from the immediate release layer within 10 min, and doxycycline hyclate release was retarded to a minimum of up to 8 h in the primary layer as well as the bilayer. Formulation also had a significant effect on both Escherichia coli and Staphylococcus aureus. Conclusion: In the current study, bilayers were successfully prepared and characterized. The optimized formulation can be effectively used for the treatment of periodontitis. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the administration of doxycycline hyclate in a long‐acting pharmaceutical preparation in pigs when administered either ad libitum as a feed medication or an oral bolus dose. In all instances, the studied dose was 20 mg/kg b.w. A total of 48 healthy crossbred, castrated male pigs (Landrace‐Yorkshire) weighing 23 ± 4.3 kg were included in this trial. They were randomly assigned to six groups as follows: two groups for the experimental prototype 1 of doxycycline hyclate administering it ad libitum (Fad‐lib) or as forced bolus (Fbolus); two groups for the experimental prototype 2 of doxycycline hyclate as for the former groups (FCad‐lib and FCbolus), and two control groups receiving the same dose of doxycycline hyclate, but of a commercial premix, also as previously explained (Cbolus and Cad‐lib). Statistical analysis of the mean pharmacokinetic values was carried out with Kruskal–Wallis and Dunn's tests. The relative bioavailability (Fr) of the best prototype, when administered ad libitum (FCad‐lib), was five times larger than the reference group (Cadlib). These results allow the proposal that the referred differences achieved in the presented prototypes can mark a notable clinical difference, particularly in pathogens with some resistance. [ABSTRACT FROM AUTHOR]

Doxycycline hyclate (DOXH) is very important to treat acne and prevent infections caused by bacteria, so quantifying doxycycline hyclate and its related substances is crucial. In this work, All analytes of doxycycline and its related substances, including methacycline, 4‐epi doxycycline, 6‐epi doxycycline, and 2‐acetyl‐2‐carbamoyl doxycycline, were successfully separated at low concentrations in a single run utilizing the suggested isocratic high‐performance liquid chromatography method with a mobile phase comprising water:acetonitrile:perchloric acid (75:25:0.2, v/v), Phenomenex Luna C18 column (50 × 4.6 mm, 3 μm i.d.) maintained at 30°C with a flow rate of 0.7 mL/min, injection volume of 25 μL, and photodiode array detector at 269 nm. DOXH and its related substances were linear in the range of 0.25–50, 0.1–30, 0.2–35, 0.5–50, and 0.6–20 μg/mL, respectively, with correlation coefficients greater than 0.999 and good accuracy results between 98% and 102%. The method has been successfully used to determine the drug's comparative study in both generic and reference products, demonstrating the similarity between the two products. According to the International Council for Harmonization requirements, the proposed approach was validated. Additionally, the technique has effectively studied in vitro dissolution, Six Sigma, and content uniformity. [ABSTRACT FROM AUTHOR]

The ternary mixture of doxycycline hyclate (DOX), ambroxol hydrochloride (AMB), and ambroxol synthetic precursor and process impurity (IMP) as chemically identified in the British Pharmacopeia as 2-amino-3, 5-dibromobenzaldehyde was examined for the first time using an ultra-performance liquid chromatographic technique. The presented work aimed to develop and validate a green accurate sensitive modern method for determination of this mixture. The obtained UPLC was accomplished by using an UPLC C18 column with mobile phase combination of acetonitrile: water (60:40, v/v) which was flowed at the rate of 0.22 mL per minute. Elution was in an isocratic manner and temperature control set at room temperature. UV was used to identify the effluent, which was injected at a volume of 5.00 µL; 370 nm for DOX and 240 nm for AMB and IMP. In concentration ranges; of (5–150) µg mL−1, linearity of both DOX and AMB was attained and of (0.5–40) µg mL−1, linearity of IMP was attained. Accuracy of this UPLC method was found to be 100.28, 99.66, and 100.36 for DOX, AMB, and IMP, respectively. ICH standards were followed while making the method validation. The existing combined pharmaceutical dosage form was analyzed by the obtained UPLC method for determination of the evaluated drugs successfully and the obtained results expressed as (Recovery % ± SD) were 101.02 ± 1.37 for DOX and 102.22 ± 1.56 for AMB. Also, the statistically significant correlation of our created approach to the reported HPLC method revealed no appreciable differences in terms of accuracy and precision. The developed method's greenness profile was appraised using many greenness metrics, green assessment comparison between the established columnar method and the published ones was made. [ABSTRACT FROM AUTHOR]

Doxycycline hyclate (DOXY) is a tetracycline derivative known as the broad-spectrum bacteriostatic drug. DOXY has been suggested as the first-line antibiotic for diabetic foot ulcers (DFU). Unfortunately, the long-term availability of DOXY in both oral and conventional topical dosage forms reduces its therapeutic effectiveness, which is closely linked to gastrointestinal side effects and acute pain during therapy, as well as uncontrolled DOXY release at the wound site. To address these shortcomings, we present for the first time a DOXY hydrogel system (DHs) built on crosslinks between carboxymethyl chitosan (CMC) and aldehyde hyaluronic acid (AHA). Three formulations of DHs were developed with different ratios of CMC and AHA, consisting of F1 (3:7, w/w), F2 (5:5, w/w), and F3 (7:3, w/w). Viscosity, rheology, gel strength, pH, swelling, gel fraction, wettability, stability, in vitro drug release, ex vivo antibacterial, and dermatokinetic studies were used to evaluate the DHs. According to the in vitro release study, up to 85% of DOXY was released from DHs via the Fickian diffusion mechanism in the Korsmeyer–Peppas model (n < 0.45), which provides controlled drug delivery. Because of its excellent physicochemical characteristics, F2 was chosen as the best DHs formulation in this study. Essentially, the optimum DHs formulation could greatly improve DOXY's ex vivo dermatokinetic profile while also providing excellent antibacterial activity. As a consequence, this study had promising outcome as a proof of concept for increasing the efficacy of DOXY in clinical therapy. Further extensive in vivo studies are required to evaluate the efficacy of this approach. [ABSTRACT FROM AUTHOR]

Borneol has been successfully employed as a gelling agent for in situ forming gel (ISG). While 40% borneol can regulate drug release, there is interest in novel approaches to achieve extended drug release, particularly through the incorporation of hydrophobic substances. Herein, triacetin was selected as a hydrophobic additive solvent for doxycycline hyclate (Dox)-loaded 40% borneol-based ISGs in N-methyl-2-pyrrolidone (NMP) or dimethyl sulfoxide (DMSO), which were subsequently evaluated in terms of their physicochemical properties, gel formation morphology, water sensitivity, drug release, and antimicrobial activities. ISG density and viscosity gradually decreased with the triacetin proportion to a viscosity of <12 cPs and slightly influenced the surface tension (33.14–44.33 mN/m). The low expelled force values (1.59–2.39 N) indicated the convenience of injection. All of the prepared ISGs exhibited favorable wettability and plastic deformation. Higher gel firmness from ISG prepared using NMP as a solvent contributed to the ability of more efficient controlled drug release. High triacetin (25%)-loaded ISG retarded solvent diffusion and gel formation, but diminished gel firmness and water sensitivity. ISG containing 5% triacetin efficiently prolonged Dox release up to 10 days with Fickian diffusion and presented effective antimicrobial activities against periodontitis pathogens such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Therefore, the Dox-loaded 40% borneol-based ISG with 5% triacetin is a potential effective local ISG for periodontitis treatment. [ABSTRACT FROM AUTHOR]

In the present study a simple, rapid, sensitive, and cost-effective stability indicating UVspectrophotometric method was developed of doxycycline hyclate in bulk form and validated as per ICH guidelines. The stability-indicating study of doxycycline hyclate was based on the forced degradation reactions of the drug under different ICH-prescribed stress conditions like acid, alkali, neutral, oxidation, thermal, and photolysis. The absorption maximum of the drug was shown at 270nm and methanol was selected as solvent on the basis of the solubility of the drug. A linear relation with a regression coefficient value (R2) of 0.999 indicates that the method follows Beer's- Lambert's law within the concentrations range of 5 - 50 µg/ml. The detection limit and quantitation limit were found to be 0.53 µg/ml and 1.55 µg/ml respectively. The % of recoveries was found to be within the range of 98.87 - 99.88 with a low % of RSD indicating the accuracy of the method for estimation of the drug. Under stressed conditions, significant degradation was found in alkali, neutral and oxidation conditions and found to be sensitive under thermal and photolytic conditions but stable to acidic hydrolytic conditions. The developed method was validated according to ICH guidelines and found accurate, precise, and specific, suggesting that the developed stability-indicating spectroscopic method could be successfully adopted to estimate doxycycline hyclate. [ABSTRACT FROM AUTHOR]

Currently, the global increase in resistance of pathogens to widely used antibiotics requires a return to the practice of using some classic drugs with preserved activity, finding new ways and directions of delivery of antibiotics to the locations of pathogenic microorganisms and the use of antimicrobial drugs that are not yet resistant. Doxycycline refers to antimicrobial drugs that do not yet have widespread resistance. Numerous studies of doxycycline have now been described as enhancing therapeutic effects, including COVID-19-related diseases, and finding new delivery routes to limit systemic side effects associated with high doses and avoid antibiotic resistance. The aim of the work was to analyze modern ways of doxycycline delivery, to determine the prospects for use in pharmacy, to summarize and systematize data on its functional purpose in the development of drugs with specified pharmaco-technological parameters. It is established that in the Ukrainian pharmaceutical market the range of drugs based on doxycycline hyclate is represented only by solid oral dosage forms - tablets and capsules for immediate release, but in the global pharmaceutical market there are additional dosage forms that provide parenteral delivery of doxycycline and oral forms. suspensions, syrups, dispersed tablets and delayed-release dosage forms – tablets, capsules and granules, which are the basis for the development of domestic drugs based on doxycycline. Development of new dosage forms with modified DH, such as implants, aerosols, lyophilisate for solution for injection, development of new manufacturing technologies, selection of excipients and delivery systems can improve the pharmacological action of antibiotics by reducing the dose and frequency of administration, prolonged or controlled programming. , and expanding the range of therapeutic action. Doxycycline is promising in pharmaceutical practice for the treatment of COVID-19, both due to its ability to inhibit matrix metalloproteinases (MMPs) and antiviral activity, especially against Mycoplasma pneumoniae, which is a secondary bacterial cause of pneumonia during the COVID-19 pandemic.

Doxycycline hyclate is an antibiotic drug with a broad‐spectrum activity against a variety of gram‐positive and gram‐negative bacteria and is frequently used as a pharmacological agent and as an effector molecule in an inducible gene expression system. A sensitive, reliable and fast spectrophotometric method for the determination of doxycycline hyclate in pure and pharmaceutical formulations has been developed using flow injection analysis (FIA) and batch procedures. The proposed method is based on the reaction between the chromogenic reagent (V4+) and doxycycline hyclate in a neutral medium, resulting in the formation of a yellow compound that shows maximum absorbance at 396 nm. In a batch procedure, the proposed method was validated over the concentration range of 1.0–80 μg mL−1 with a sampling frequency of 30/h, and commercial pharmaceutical samples were successfully determined. The proposed method was successfully adapted with an FIA system where the peak heights are proportionally connected to doxycycline hyclate over the concentration range of 25–400 μg mL−1 with a sampling frequency of 50/h. The limits of detection (LOD) and quantification (LOQ) were 0.9 and 10.44 μg mL−1 and 3.01 and 34.81 μg mL−1 for batch and FIA respectively. The samples were submitted to an HPLC analysis, and the outcomes demonstrated excellent agreement with the suggested procedures. The adopted FIA procedure allows fast monitoring of doxycycline hyclate in pharmaceutical formulations and it can be used for quality control purposes during the production processes of doxycycline hyclate. [ABSTRACT FROM AUTHOR]

Modulation with the suppression of infection and inflammation is essential to the successful treatment of periodontitis. An aqueous insoluble hydrophobic anti-inflammatory compound, i.e., ibuprofen (IBU), was investigated in this study as the matrix-forming agent of a doxycycline hyclate (DH)-loaded solvent removal-induced in situ forming gel (ISG) using dimethyl sulfoxide (DMSO) and N-methyl pyrrolidone (NMP) as the solvents. Their physicochemical properties, including pH, density, viscosity, surface tension, contact angle, water tolerance, injectability, mechanical properties, gel formation, and drug release, were determined. Their antimicrobial activities were tested using agar cup diffusion, and their anti-inflammatory activity was assessed using thermal inhibition of protein denaturation of egg albumin. Increasing the IBU content decreased the density, pH, surface tension, and contact angle but increased the viscosity, force and work of injection, and gel formation of IBU-based ISG solution. Although their water tolerance values decreased with the increase in IBU content, the addition of DH and the use of NMP led to high water tolerance. The characterization of the dried gel remnants of ISGs presented no change in IBU crystallinity and thermal properties and confirmed no chemical interaction among the components of ISGs. The obtained transformed IBU matrix prolonged the release of DH and IBU from ISGs over 7 days from its tortuously packed IBU matrix with small pores, and conformed well with Fickian diffusion mechanism. The developed DH-loaded solvent removal-induced IBU-based ISGs exhibited efficient antimicrobial activities against Staphylococcus aureus, methicillin-resistant S. aureus, Escherichia coli, Candida albicans, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. IBU in formulation promoted the antimicrobial activity of ISGs, whereas DH and NMP promoted the anti-inflammatory activity of ISGs. Consequently, the DH-loaded solvent removal-induced IBU-based ISGs proposed in this study show great potential as an effective bioactive drug delivery system for periodontitis treatment by localized periodontal pocket injection. [ABSTRACT FROM AUTHOR]

Thermogelling amphiphilic block copolymers have been widely investigated in the development of pharmaceutical drug carriers. In particular, thermosensitive gels based on poloxamer 407 (P407) have great potential for periodontal disease treatment, thanks to their ability to be liquid at room temperature and become viscous gels at body temperature. However, some problems, related to short in situ residence time, reduce their feasible clinical use. Thus, in order to improve the effective applicability of these materials, we studied how P407 thermogels are affected by the pH and by the inclusion of different hydrophilic polymers, used as excipients for increasing the gel stiffness. For this scope, a complete chemical-physical characterization of the synthesized gels is provided, in terms of determination of sol-gel transition temperature, viscosity and erosion degree. The data are correlated according to a statistical multivariate approach based on Principal Component Analysis and their mucoadhesion properties are also tested by Tapping mode-Atomic Force Microscopy (TM-AFM) imaging. Finally, we studied how the different P407 formulations are able to influence the release pathway of two antibacterial drugs (i.e., chlorhexidine digluconate and doxycycline hyclate) largely used in oral diseases. [ABSTRACT FROM AUTHOR]

According to World Health Organization (WHO) 10% of the medicines in the Low and Middle Income Countries (LMICs) are of poor quality posing a major public health threat. One way to circumvent such problem is the development and deployment of rapid, economical and efficient analytical methods. Hence this research aims to develop a High-Performance Thin Layer Chromatography (HPTLC) method for the determination of doxycycline hyclate. A rapid and simple HPTLC method with densitometry detection at 360 nm to determine doxycycline hyclate in capsules and tablet formulations was developed and validated. HPTLC was performed on glass plates coated with C18 reverse phase silica gel 60 F254 and pretreated with 0.27 M ethylenediaminetetraaceticacid (EDTA) solution. The mobile phase was dichloromethane: methanol: acetonitrile: 1% aqueous ammonia in the ratio of 10:22:53:15 (v/v). The linearity range lies between 200 and 1,000 ng/spot with correlation coefficient of 0.997. The Rf value is 0.5 ± 0.02%. Recoveries were in the range of 94.50–100.5%. Limit of detection and limit of quantitation values for doxycycline hyclate were 40 and 160 ng/spot respectively. The developed method was validated as per ICH guidelines. Thus, it was found to be accurate, precise, specific and robust. In forced degradation study, doxycycline hyclate was found to degrade in acidic and alkaline media, and through oxidative stress. The drug was found to be relatively stable to heat and photo degradation. The method was successfully applied for the routine quantitative analysis of dosage forms containing doxycycline hyclate. The developed method offered comparable results (as confirmed by F-test) with that of the HPLC pharmacopoeial (BP) analysis method. [ABSTRACT FROM AUTHOR]

• The addition order of drugs will have different effects on binding affinity. • The binding site changes when two drugs bind to trypsin/pepsin simultaneously. • The two drugs show a moderate affinity with trypsin/pepsin. • The free concentration of two drugs in ternary system is higher than binary system. • The effect of ternary system on trypsin/pepsin backbone is greater than binary system. The interaction mechanism of trypsin/pepsin-doxycycline hyclate-quercetin ternary system was investigated by the molecular docking, molecular dynamics simulation and multiple spectroscopic methods. The results show that when doxycycline hyclate and quercetin are bound with trypsin/pepsin in sequence to form the ternary system, the different sequence of doxycycline hyclate/quercetin binding has different effects on the binding affinity of the two drugs and trypsin/pepsin. However, the binding site of the two drugs on trypsin/pepsin is basically the same as that of the corresponding binary system, except for pepsin-doxycycline hyclate (first)-quercetin ternary system. For the trypsin-quercetin (first)-doxycycline hyclate ternary system, the activity of trypsin is inhibited due to the presence of quercetin. The doxycycline hyclate that binding first even affects the binding site of quercetin and the inhibition of pepsin activity. When doxycycline hyclate and quercetin bind with trypsin/pepsin at the same time, the binding site of doxycycline hyclate and quercetin on trypsin/pepsin is completely different from their corresponding binary system. The values of binding constant of 104 L mol−1 indicate that the binding affinity are all moderate. In ternary system, the free concentration of doxycycline hyclate and quercetin in trypsin/pepsin is higher than that in binary system. Hydrophobic interactions, electrostatic forces and hydrogen bonds are the main non-covalent forces. The extent of unfolding of trypsin/pepsin peptide backbone in ternary system is greater than that in binary system. The effects of binary and ternary systems on the secondary structure of trypsin/pepsin are not significantly different, and both results in the reduction of trypsin/pepsin β-sheet. [Display omitted] [ABSTRACT FROM AUTHOR]

Borneol has been successfully employed as a gelling agent for in situ forming gel (ISG). While 40% borneol can regulate drug release, there is interest in novel approaches to achieve extended drug release, particularly through the incorporation of hydrophobic substances. Herein, triacetin was selected as a hydrophobic additive solvent for doxycycline hyclate (Dox)-loaded 40% borneol-based ISGs in N-methyl-2-pyrrolidone (NMP) or dimethyl sulfoxide (DMSO), which were subsequently evaluated in terms of their physicochemical properties, gel formation morphology, water sensitivity, drug release, and antimicrobial activities. ISG density and viscosity gradually decreased with the triacetin proportion to a viscosity of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Therefore, the Dox-loaded 40% borneol-based ISG with 5% triacetin is a potential effective local ISG for periodontitis treatment.

Arsenic is a widespread environmental contaminant known to accumulate in the brain, leading to cognitive impairment. However, the exact mechanisms by which arsenic causes cognitive deficits remain unclear. The present study aims to discover whether the destruction of the blood-brain barrier (BBB) mediated by matrix metalloproteinases 2 and matrix metalloproteinases 9 (MMP-2 and MMP-9) and subsequent neuronal apoptosis are involved in arsenic-induced cognitive impairment. Ninety male mice were given 0, 25, and 50 mg/L NaAsO 2 in drinking water and 30 mg/kg doxycycline hyclate (DOX, an inhibitor of MMPs) gavage for 12 weeks to observe the alterations in learning and memory of mice, the morphology of hippocampal neurons, as well as the BBB permeability and ultrastructure, the localization and expression of tight junction proteins, MMP-2, and MMP-9. Our findings indicated that arsenic exposure induced learning and memory impairment in mice, accompanied by neuronal loss and apoptosis. Furthermore, arsenic exposure increased hematogenous IgG leakage into the brain, disrupted the tight junctions, reduced the expression of Claudin5, Occludin, and ZO1 in the endothelial cells, and increased the expression of MMP-2 and MMP-9 in the endothelial cells and astrocytes. Finally, DOX intervention preserved BBB integrity, alleviated hippocampal neuronal apoptosis, and improved cognitive impairment in mice caused by arsenic exposure. Our research demonstrates that cognitive disfunction in mice induced by arsenic exposure is associated with MMP-2 and MMP-9-mediated BBB destruction and neuronal apoptosis. The current investigation provides new insights into mechanisms of arsenic neurotoxicity and suggests that MMP-2 and MMP-9 may serve as potential therapeutic targets for treating arsenic-induced cognitive dysfunction in the future. [Display omitted] • Arsenic induced cognitive impairment via BBB disruption and neuronal apoptosis. • Arsenic increased BBB permeability and degradation of tight junction proteins. • DOX, an inhibitor of MMP-2 and MMP-9, protected arsenic-induced BBB integrity. • DOX ameliorated arsenic-induced cognitive impairment in mice. [ABSTRACT FROM AUTHOR]

In this study, two soil fungi from ruminant farms soil that has been exposed to tetracycline antibiotic with GPS coordinate 2°59'28.8"N 101°44'00.5"E were isolated and identified. Identification was carried out based on morphological observations, macroscopic, microscopic and molecular identification, polymerase chain reactions (PCR) and sequencing. The isolated species were identified as Purpureocillium lilacinum strain PlHN17 (S1) and Trichoderma asperellum isolate Tullur (S12). Growth profiles for each of the isolated fungi were constructed and the fungi showed exponential phase from day 4 to day 5. Both fungi went through a biodegradation process and antimicrobial activity of doxycycline hyclate antibiotic residues was determined. The finding revealed P. lilacinum strain PlHN17 (S1) has the highest deactivation ability of doxycycline hyclate antibiotic (77.78 %) compared to T. asperellum isolate Tullur (75.45 %). Hence, the isolated P. lilacinum strain PlHN17 (S1) showed the potential as a bioremediation tool to deactivate the doxycycline hyclate antibiotic. [ABSTRACT FROM AUTHOR]

Polymeric material plays an important role as a matrix former in the modulation of drug release of antimicrobial-loaded in situ forming gel (ISG) for efficient periodontitis treatment. This study was conducted to compare three polymers, namely bleached shellac (BS), Ethocel (EC) and Eudragit RS (ERS), as matrix formers of doxycycline hyclate (DH)-loaded solvent exchange-induced ISG. All prepared ISGs, except 25% EC ISG, exhibited the Newtonian flow behaviour. Transformation from solution into matrix-like was achieved rapidly within 5 min. Increasing the amount of these polymers extended the release of DH. DH-loaded EC and ERS ISG systems exhibited high antimicrobial activity, and all ISGs were effective in inhibiting the growth of Staphylococcus aureus, Escherichia coli, Streptococcus mutans, Porphyromonas gingivalis and Candida albicans. By comparison, the DH-loaded ERS ISG, through the solvent exchange mechanism, was found to be ease in injection with low viscosity and sustained the release with higher concentration, meanwhile, it also exhibited interesting in vitro degradability and antimicrobial activities. Therefore, the DH-loaded ERS ISG exhibited a potential use for localized periodontal drug delivery system for the treatment periodontitis.

The clinical efficiency of the antibiotic is determined by its distribution in organs and tissues, the ability to penetrate the physiological and pathological barriers of the body. The article presents the results from a study of the intake, distribution, and excretion of doxycycline hyclate – the active substance of the antibiotic pollodoxin from the body of broiler chickens (the Cobb-500 cross) with ornithobacteriosis. It has been established that 24 hours after the pollodoxin solution application in broiler chickens with ornithobacteriosis, the highest content of its active substance (doxycycline hyclate) was found in the lungs, liver, slightly less – in the kidneys, and least – in the heart and pectoral muscles. After 48 and 72 hours, the content of doxycycline hyclate increases in the liver, kidneys, heart, and pectoral muscles compared to 24 hours, while in the lungs decreases slightly after 48 hours and does not differ from it after 72 hours. At 96 hours, the content of doxycycline hyclate in the kidneys, lungs, and pectoral muscles reaches maximum values; in the liver it is smaller than the previous one (72 hours), while in the heart it does not differ from it. Doxycycline hyclate does not show cumulative properties and “organ affiliation” during 96 hours of entry into the body of broiler chickens with ornithobacteriosis. After 24 hours of discontinuation of pollodoxin use (120 hours of the experiment), the content of doxycycline hyclate in all studied organs decreases but remains high enough, indicating a relatively long elimination half-life and antimicrobial action. Pharmacokinetic indicators will allow the doctor to determine an effective drug that will provide a therapeutic effect and will prevent the development of resistance of microorganisms

The article presents the results of studies of the effect of fenbenzyl and fenbendazole on the antioxidant status in dogs under the experimental infection with a causative agent of toxocariasis. Experiments were performed on 18 dogs, two and four months old. Three groups of six animals in each were formed: control and two experimental. Puppies in all groups were experimentally infected with causative agent of toxocariasis at a dose of 5.000 embryonated Toxocara canis eggs per kg of body weight. The control group of dogs was as untreated control. Puppies of the first experimental group were fed with the drug fenbendazole at a dose of 150 mg per 3 kg of body weight once a day for three days in a single dose. Puppies of the second experimental group were fed with the drug fenbenzyl at a dose of 350 mg per 3 kg of body weight once a day for three days. While studying the activity of the enzymatic part of the antioxidant defense system, namely catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, as well as a non-enzymatic part: the level of reduced glutathione, an increase in the activity of these indicators was found in animals of experimental groups. It should be noted that the application of the drug fenbenzyl in infected dogs contributed to a better normalization of the antioxidant system in animals than the use of the drug fenbendazole. The use of fenbenzyl in infected dogs contributed to a more likely increase in the antioxidant status in dogs of the second experimental group, as this drug includes milk thistle that exhibits antioxidant properties due to the presence of silymarin, which restores damaged liver cells. Studies confirm the effectiveness of the use of milk thistle in drug fenbenzyl in dogs with the development of toxocariasis infection to activate the protective systems of their body

Doxycycline hyclate is Biopharmaceutical Classification System, class I drug (high solubility and high permeability), but it is associated with poor photostability. It is in the class of tetracycline antibiotic, which is used to treat various infections, but its bioavailability is compromised due to its sensitivity to light and aqueous instability. In this paper, the influence of inclusion complexation with different cyclodextrins, i.e., αCD, γCD, HPβCD and RMβCD, on the photostability of doxycycline hyclate in aqueous media was investigated. Host–guest inclusion complexes were prepared by freeze- drying method. The prepared complexes were characterized for drug content, SEM, XRPD, in vitro permeation studies and photostability studies. XRPD showed diffused peaks for most of the complexes, while SEM showed irregularly shaped particles. The formulation D20 (Drug: γCD in 1:20 molar ratio) showed the highest % drug content (83.72 ± 1.2%), and the formulations D1 (Drug: αCD in 1: 2 molar ratio) showed the lowest % drug content among all the CD complexes. It was found that the photodegradation of the drug was reduced significantly upon complexation. For Drug: CD complexes, the photostability of the aqueous solution of drug/CD complexes was found to be in the order of γCD > RMβCD > HPβCD > αCD with maximum photostability shown by Drug: γCD (1:20 molar ratio) complex. The obtained results suggested that cyclodextrin complexation can be used as an alternative approach for increasing the photostability of doxycycline hyclate. [ABSTRACT FROM AUTHOR]

Modulation with the suppression of infection and inflammation is essential to the successful treatment of periodontitis. An aqueous insoluble hydrophobic anti-inflammatory compound, i.e., ibuprofen (IBU), was investigated in this study as the matrix-forming agent of a doxycycline hyclate (DH)-loaded solvent removal-induced in situ forming gel (ISG) using dimethyl sulfoxide (DMSO) and N-methyl pyrrolidone (NMP) as the solvents. Their physicochemical properties, including pH, density, viscosity, surface tension, contact angle, water tolerance, injectability, mechanical properties, gel formation, and drug release, were determined. Their antimicrobial activities were tested using agar cup diffusion, and their anti-inflammatory activity was assessed using thermal inhibition of protein denaturation of egg albumin. Increasing the IBU content decreased the density, pH, surface tension, and contact angle but increased the viscosity, force and work of injection, and gel formation of IBU-based ISG solution. Although their water tolerance values decreased with the increase in IBU content, the addition of DH and the use of NMP led to high water tolerance. The characterization of the dried gel remnants of ISGs presented no change in IBU crystallinity and thermal properties and confirmed no chemical interaction among the components of ISGs. The obtained transformed IBU matrix prolonged the release of DH and IBU from ISGs over 7 days from its tortuously packed IBU matrix with small pores, and conformed well with Fickian diffusion mechanism. The developed DH-loaded solvent removal-induced IBU-based ISGs exhibited efficient antimicrobial activities against Staphylococcus aureus, methicillin-resistant S. aureus, Escherichia coli, Candida albicans, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. IBU in formulation promoted the antimicrobial activity of ISGs, whereas DH and NMP promoted the anti-inflammatory activity of ISGs. Consequently, the DH-loaded solvent removal-induced IBU-based ISGs proposed in this study show great potential as an effective bioactive drug delivery system for periodontitis treatment by localized periodontal pocket injection.

The objectives of this study were to investigate the pharmacokinetics (PK), pharmacodynamics (PD), and the efficacy of oral administration of doxycycline (DXC) in horses with Streptococcus zooepidemicus tissue infections. Tissue chambers (TC) were implanted subcutaneously in the cervical region of 7 horses and inoculated with a single S. zooepidemicus isolate with a minimum inhibitory concentration (MIC) of 0.25 µg/ml, determined by agar dilution. Doxycycline hyclate (10 mg/kg, orally, q 12 h, for 5 days) mixed with poloxamer gel was started following inoculation. The TC fluid was sampled prior to and following inoculation for cytology analysis, quantitative culture, and DXC determination. Plasma DXC concentrations were measured over 48 h following the last dose of DXC administered. The mean plasma peak concentration (Cmax) of DXC was 0.32 µg/ml, and concentrations above the MIC were only reached in 3 TC samples. In plasma, mean T > MIC was 2.4 h, mean Cmax/MIC was 1.30, and mean AUClast/MIC was 11.63 h. These PK/PD indices did not reach the suggested targets for DXC treatments of infections, and the TC abscessed in all horses. This is the first study to evaluate the recommended dose of DXC in horse in an infection model. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel spectrophotometric methods for analysis of new mixture with chemical precursor. • Smart HPTLC method for analysis of new mixture with chemical precursor. • Evaluation of the greenness profile of the developed methods. • The developed methods are economic, energy saving and ecofriendly methods. • Green comparison between the developed methods and reported one. Recently, Countless people have become affected as a result of the Covid-19 crisis. Even after recovery, COVID-19 can lead to respiratory difficulties and lung impairment consequently; bacterial infections have a good possibility of infiltrating our respiratory system due to reduction in respiratory immunity. Therefore, the importance of the chosen mixture of doxycycline and ambroxol becomes clear here curing bacterial illnesses invade respiratory tract. The ternary blend of (DOX) doxycycline hyclate, (AMB) ambroxol hydrochloride, (IMP) chemical ambroxol precursor, and pharmacopeial impurity was quantified using four contemporary, selective, and straightforward methods. Method (I) was area under the curve spectrophotometric method (AUC), where zero order absorption spectra were used for calculating the area under the curve of AMB, IMP, and DOX in ranges of 205–219, 222–245, and 264–290 nm, respectively. Each component's absorptivity values (a) at the chosen area were computed. Method (II) was differential dual wavelength (DDW), where upon collecting the first derivative spectra of AMB, IMP, and DOX, amplitudes at 252–263.4, 236–246.6, and 388.8–420 nm were subtracted, consecutively. Method (III) the mean centering of ratio spectra spectrophotometric method (MCR), peak to peak amplitudes on these resulted spectra were measured at (258.2 and 258.4 nm) for AMB, (264.4 and 264.6 nm) for IMP, and at (230.4 and 230.6 nm) for DOX. In addition, method (IV) HPTLC using a stationary phase made of silica gel HPTLC plates that had been pre-treated with 0.27 M di-sodium-EDTA (pH 9 with 21 % sodium hydroxide). The platform is developed using the eluent of ethyl acetate, acetone, distilled water, and acetic acid (9:2:0.7:0.55, by volume) and scanning by employing ultraviolet light regarding AMB and IMP at 254 nm while DOX at 380 nm. For validating the developed procedures, ICH principles were adhered to. The proposed methods were successful in studying dosage form containing investigated substances. The developed techniques' greenness features were assessed using a variety of greenness parameters, and an environmental evaluation comparison between the current methods and the reported one was done. Obtained methods' statistical analyses were also performed. [ABSTRACT FROM AUTHOR]

Purpose: Different compositions of copper oxide (CuO)-doped calcium silicate clusters wereused to treat the cancer cells.Methods: The influence of CuO content on the morphology, drug delivering ability,physicochemical properties and cytotoxicity was investigated.Results: The microcrystalline structure revealed the decrement of the size from (20-36 nm) to(5-7 nm) depending on the copper content percentages. Drug delivering ability of doxycyclinehyclate (Dox) was down regulated from 58% to 28%in the presence of the CuO. The inclusionof CuO and Dox didn’t show any remarkable changes on the physicochemical properties of theCuO-doped calcium silicate nanoparticles.Conclusion: The CuO-doped calcium silicate sample (5 weight %) exhibited great cytotoxicityagainst the tested cell lines compared to the CuO-free sample. CuO-doped materials displayedsignificant anticancer effect; this sheds light on its implication in the treatment of cancer.

Background:Periodontal instrumentation is accessible to a certain limit, as subgingival calculus is difficult to remove completely in cases of deep pockets and furcation defects. Host modulating agents aim to inhibit arachidonic acid pathways, modulate MMPs, bone remodeling, and regulate immune and inflammatory responses. This systematic review aimsto find the effects of Low Dose Doxycycline (LDD) as local drug delivery systems and sub-antimicrobial dose doxycycline for the treatment of periodontal disease. Material And Methods: Electronic database searched were: Pubmed, Medline, Scopous and Ebsco was performed using MeSH terms: low dose doxycycline, subantimicrobial dose doxycycline, chemically modified doxycycline, doxycycline, doxycycline hyclate, atridox and periostat. Articles published between years 2008-2019 were reviewed. Result: A Systematic review methodology was followed and database searching was done which yields 422 records. Records from year 2008 - 2019 were taken into consideration. After inclusion and exclusion accordingly, A total of 10 studies were systematically reviewed. Non surgical or surgical periodontal therapy is more effective in reducing periodontal disease when low dose doxycycline is used as an adjunct either locally or systematically delivered. Conclusion: Subantimicrobial Dose Doxycycline (SDD) is commonly accepted as a host response modifier and it Subantimicrobial Dose Doxycycline (SDD) which down regulates the activity of MMPs. Also, doxycycline provides long-term post-treatment effects. Based in the inference drawn from this systematic review, non surgical or surgical periodontal therapy is more effective in reducing periodontal disease when low dose doxycycline is used as an adjunct, delivered either locally or systematically. [ABSTRACT FROM AUTHOR]

The objective of this study was to prepare and evaluate the doxycycline hyclate containing bigel for the effective treatment of acne. Bigels are biphasic systems formed by water-based hydrogels and oil-based organogel. Carbopol 940 was used to prepare the hydrogel phase, whereas Span-60 and olive oil for the oleogel phase. The microstructure of bigel confirmed the oil in water type emulsion formation. The average droplet size of formulations was found 15–50 µm, and a bell-shaped droplet distribution curve, rheological, or viscosity studies suggested that the consistency and stability of bigel decrease with high organogel concentration. Three formulations (F1, F2, and F3) of the different ratios of hydrogel:oleogel (60:40, 70:30, and 80:20) were prepared in which F1 was less stable compared to F2 and F3. The drug content of F2 and F3 was respectively 79.94 and 71.33%. Formulation F2 was found more effective as compared to F3 based on in vitro drug release studies. Bigel also showed better results during in vivo studies at the rabbit ear model, which reduce acne diameter up to 1.10 mm from 4.9 mm while gel reduced it up to 1.20 mm. [ABSTRACT FROM AUTHOR]

The ar􀆟cle presents the results of studies of the effect of fenbenzyl and fenbendazole on the an􀆟oxidant status in dogs under the experimental infec􀆟on with a causa􀆟ve agent of toxocariasis. Experiments were performed on 18 dogs, two and four months old. Three groups of six animals in each were formed: control and two experimental. Puppies in all groups were experimentally infected with causa􀆟ve agent of toxocariasis at a dose of 5.000 embryonated Toxocara canis eggs per kg of body weight. The control group of dogs was as untreated control. Puppies of the first experimental group were fed with the drug fenbendazole at a dose of 150 mg per 3 kg of body weight once a day for three days in a single dose. Puppies of the second experimental group were fed with the drug fenbenzyl at a dose of 350 mg per 3 kg of body weight once a day for three days. While studying the ac􀆟vity of the enzyma􀆟c part of the an􀆟oxidant defense system, namely catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, as well as a non-enzyma􀆟c part: the level of reduced glutathione, an increase in the ac􀆟vity of these indicators was found in animals of experimental groups. It should be noted that the applica􀆟on of the drug fenbenzyl in infected dogs contributed to a be􀆩er normaliza􀆟on of the an􀆟oxidant system in animals than the use of the drug fenbendazole. The use of fenbenzyl in infected dogs contributed to a more likely increase in the an􀆟oxidant status in dogs of the second experimental group, as this drug includes milk thistle that exhibits an􀆟oxidant proper􀆟es due to the presence of silymarin, which restores damaged liver cells. Studies confirm the effec􀆟veness of the use of milk thistle in drug fenbenzyl in dogs with the development of toxocariasis infec􀆟on to ac􀆟vate the protec􀆟ve systems of their body. [ABSTRACT FROM AUTHOR]

Currently, periodontitis is treated by oral dosage forms (antibiotics) which shows systemic side effects and failed to reach the therapeutic concentration (above minimum inhibitory concentration, MIC) in the periodontal pocket. The present study aimed to overcome the above issues, by designing tailored doxycycline hyclate laden in situ gel by Poloxamer 407, chitosan, and polyethylene glycol 600. The in situ gel-forming system has attracted attention owing to its ability of sustained drug release above MIC, easy administration (syringeability), and high drug retention (localization) in the periodontal cavity. The Box-Behnken design (BBD) was used to tailor and optimize the concentration of Poloxamer 407 (X1 = 14.3%), chitosan (X2 = 0.58%), and polyethylene glycol 600 (X3 = 1.14%) to achieve sufficient syringeability (149 N), t90% (1105 min), and viscosity at non-physiological condition (512 cps) and physiological condition (5415 cps). The optimized in situ gel was clear and isotonic (RBCs test). The gelation temperature of the optimized in situ was 34 ± 1°C with sufficient mucoadhesive strength (26 ± 2 dyn/cm2), gel strength (29 ± 2 sec), and texture profile for periodontal application. The in vitro drug release studies showed sustain release from optimized in situ gel (24h) in comparison to marketed gel (7h). The antimicrobial activity (cup plate technique) of the in situ gel was equivalent to the marketed doxycycline gel, which suggests that the doxycycline hyclate retained its antimicrobial efficacy when formulated as in situ gelling system. In conclusion, BBD was effectively utilized to optimize in situ gel with minimum level of polymers to achieve the required characteristics of the in situ gel for sustaining drug delivery to treat periodontitis. [ABSTRACT FROM AUTHOR]

Polymeric material plays an important role as a matrix former in the modulation of drug release of antimicrobial-loaded in situ forming gel (ISG) for efficient periodontitis treatment. This study was conducted to compare three polymers, namely bleached shellac (BS), Ethocel (EC) and Eudragit RS (ERS), as matrix formers of doxycycline hyclate (DH)-loaded solvent exchange-induced ISG. All prepared ISGs, except 25% EC ISG, exhibited the Newtonian flow behaviour. Transformation from solution into matrix-like was achieved rapidly within 5 min. Increasing the amount of these polymers extended the release of DH. DH-loaded EC and ERS ISG systems exhibited high antimicrobial activity, and all ISGs were effective in inhibiting the growth of Staphylococcus aureus , Escherichia coli , Streptococcus mutans , Porphyromonas gingivalis and Candida albicans. By comparison, the DH-loaded ERS ISG, through the solvent exchange mechanism, was found to be ease in injection with low viscosity and sustained the release with higher concentration, meanwhile, it also exhibited interesting in vitro degradability and antimicrobial activities. Therefore, the DH-loaded ERS ISG exhibited a potential use for localized periodontal drug delivery system for the treatment periodontitis. [ABSTRACT FROM AUTHOR]

The intermolecular interactions of the antibiotic drug doxycycline hyclate in water, aqueous solutions of glycine and aqueous solutions of l-alanine were determined by using volumetric and acoustic methods at four different temperatures (305.15, 310.15, 315.15 and 320.15) K. The limiting partial molar volume (V ϕ o) , limiting standard partial molar volume of transfer (Δ tr V ϕ o) , limiting partial molar adiabatic compressibility ( κ ϕ , s o) and limiting partial molar adiabatic compressibility of transfer (Δ tr κ ϕ , s o) were calculated from the density and ultrasonic velocity data at different temperatures and the results suggest strong solute–solvent interactions. The caging effect of doxycycline hyclate in water and in aqueous solutions of glycine and aqueous solutions of l-alanine was studied using the positive values of E ϕ o = δ V ϕ o δ T . The structure making behavior of doxycycline hyclate in water, aqueous solutions of glycine and aqueous solutions of l-alanine was analyzed from the positive values of Hepler's constant i.e. δ 2 V ϕ o δ T 2 . The limiting isobaric thermal expansion coefficient α o = E ϕ o V ϕ o , intermolecular free length (Lf) and acoustic impedance (Z) of doxycycline hyclate in water, aqueous solutions of glycine and aqueous solutions of l-alanine were also calculated at the studied temperatures. [ABSTRACT FROM AUTHOR]

This study involves the development of spectrophotometric method for determination of microgram a suggested mounts of doxycycline Hyclate (DCH) via oxidative coupling with 2,4,dinitrophenylhydrazine reagent (2,4-DNPH) in presence of potassium periodate(KIO4) in the alkaline medium (pH 12.6) to form a red colored dye which soluble in water and gives the highest intensity of absorption at λmax 528 nm. The method has been obeyed Beer's law in the concentration range 5-60 μg.ml-1with the molar absorptivity of 10771 L. mol-1. cm-1, Sandel Index value 0.0476 μg.cm-2 with the relative standard deviation of the method does not exceed its value 1.043 % and the correlation coefficient 0.998. The proposed method was applied successfully for the determination of doxycycline hyclate in its Pharmaceutical samples (Capsule).

The experimental values of density, ρ and speed of sound, u of doxycycline hyclate drug (0.002–0.014) mol kg−1 in water and (0.1, 0.2 and 0.4) mol kg−1 of aqueous galactitol solutions at temperatures T = (303.15, 308.15 and 313.15) K and at atmospheric pressure have been reported in the present communication. From the experimental values, various derived parameters such as apparent molar volume (ΦV), apparent molar isentropic compression (ΦK), limiting apparent molar volume ( Φ v o $\phi_{\text{v}}^{\text{o}}$), limiting apparent molar isentropic compression ( Φ K o $\phi_{\text{K}}^{\text{o}}$), limiting apparent molar volume of transfer (Δ Φ V O $\phi_{\text{V}}^{\text{O}}$), limiting apparent molar isentropic compression of transfer (Δ Φ K O $\phi_{\text{K}}^{\text{O}}$), limiting apparent molar expansibility ( Φ E o $\phi_{\text{E}}^{\text{o}}$), thermal expansion coefficient (α) and acoustic parameters like isentropic compressibility (κ S) $({{\kappa}_{\text{S}}})$ , intermolecular free length (Lf), and specific acoustic impedance (Z) were calculated. The structure-making behaviour of DH in aqueous galactitol solution was determined on the basis of Hepler's Equation i.e. on the basis of sign of ( d 2 Φ V O d T 2) P ${\left({\frac{{{{\text{d}}^{2}}\phi_{\text{V}}^{\text{O}}}}{{{\text{d}}{{\text{T}}^{2}}}}}\right)_{\text{P}}}$. The various derived parameters were utilised to interpret the molecular interactions i.e. solute–solute and solute–solvent existing in the studied system. [ABSTRACT FROM AUTHOR]

There is growing demand for simple to operate, sensitive, on-site quantitative assays to investigate concentrations of drug molecules in pharmaceutical preparations for quality assurance. Here, we report on the development of two colorimetric analysis methods for the study the antibiotic doxycycline hyclate (DOX) and the nasal decongestant oxymetazoline hydrochloride (OXY), in solution as well as in their respective formulations. We compare a UV/vis spectrophotometry method with a color change recorded on a microfluidic paper-based analytical device (μPAD). Detection is based on the pharmaceutical compounds coupling with diazotized 4-aminoacetophenone (DAAP) under alkaline conditions to produce colored azo-dye products. These azo-compounds were monitored by absorbance at 425 nm for DOX and 521 nm for OXY, with linear calibration graphs in the concentration range of 0.5–35 mg L−1 (DOX) and 1.0–40 mg L−1 (OXY) and limits of detection of 0.24 mg L−1 (DOX) and 0.32 mg L−1 (OXY). For the μPAD method, color intensity was measured from photographs and a linear increase was observed at concentrations from above approximately 15 mg L−1 for both compounds and up to 35 mg L−1 for DOX and 40 mg L−1 for OXY. The developed methods were also applied to the formulated pharmaceuticals and no interference was found from the excipient. Thus, the paper-based device provides an inexpensive, simple alternative approach for use outside centralized laboratories with semi-quantitative capability. Image 1 • Azo-coupling using 4-aminoacetophenone for colorimetric analysis of pharmaceuticals. • Semi-quantitative detection of pharmaceutical products using paper-based platform. • Real time analysis of active component within pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

Purpose. Comparative studies of the release profiles of doxycycline hyclate from hard gelatine capsules, developed with the active ingredient of alternative manufacturers. Methodology. The object of the study is samples of the drug doxycycline hyclate in the form of hard gelatin capsules made from an API of an approved manufacturer "Kaifeng Pharmaceutical Group Co. Ltd", China and an alternative manufacturer "Hebei Jiupeng Pharmaceutical Co., Ltd.", China. The study of the profiles of the release of the active substance from the drug was carried out using the "Paddle apparatus". The amount of the released substance was determined by the absorption spectrophotometry method. Findings. A drug was investigated in hard gelatin capsules of 100 mg based on the substance of doxycycline hyclate from two manufacturers "Kaifeng Pharmaceutical Group Co. Ltd", China, and "Hebei Jiupeng Pharmaceutical Co., Ltd", China. It was found that according to the profile of impurities and the results of quality indicators, the substances of doxycycline hyclate from the studied manufacturers are alternative and interchangeable. To confirm the similarity of the dissolution profiles of doxycycline, 100 mg capsules were tested in accordance with the requirements of the State Pharmacopoeia Department, 2.9.3. Dissolution test, using solutions at three pH values: pH 1.0 (0.1 M HCl), pH 4.6 (acetate buffer) and pH 6.8 (phosphate physiological buffer). Comparative studies in vitro for two batches of the medicinal product established the similarity of the kinetics of the release of the active substance. The calculated values of the similarity factor are: f2 = 78.4 for a solution with pH = 1.2; f2 = 82.7 for a solution with pH = 4.6 and f2 = 75.8 for a solution with pH = 6.8. According to studies in three buffer solutions, the similarity coefficient is in the range from 50 to 100, which allows it to conclude that the studied API manufacturers can be used as alternatives for the production of the drug doxycycline hyclate in hard gelatin capsules of 100 mg. The relative standard deviation of the mean (RSD) release rate is less than 20% at the first control point and not more than 10% from the second to the last control point, indicating that the results are valid. Originality. It has been proven that the study of the dissolution profiles of solid dosage forms in vitro makes it possible to assess the risks of using APIs synthesized by various manufacturers. Practical value. The obtained results of the experiment allow manufacturers of finished medicines to reasonably use alternative manufacturers of raw materials to ensure uninterrupted industrial production and meet market demand. [ABSTRACT FROM AUTHOR]

The aim of this present clinical and microbiological study was to evaluate the efficacy of the association of locally delivered 10% doxycycline hyclate (Atridox®) with scaling and root planing in the periodontal treatment of smokers. Forty-five patients with chronic periodontitis having a minimum of two periodontal pockets (>5 mm) and satisfying the inclusion and exclusion criteria were selected. Sites were randomly assigned to scaling and root planing (SRP) or scaling and root planing followed by local application of 10% doxycycline hyclate (SRP-D). Plaque index (PI), gingival index (GI), periodontal pocket depth (PD), clinical attachment level (CAL) and total anaerobic colony count (TACC) were recorded at baseline, one month and three months respectively. Differences between baseline and each period were considered for analysis. There was a significant reduction in plaque score, gingival score, periodontal pocket depth and total anaerobic colony count from baseline in both groups at all time intervals. Clinical attachment level showed a significant gain in both groups. However, PD reduction (P < 0.001) and CAL gain (P < 0.001) were significant in the test group as compared to control at the end of 3 months. Reduction in total anaerobic colony count from baseline was significant (P = 0.02) in the test group compared to control at the end of 3 months. The use of locally delivered doxycycline may constitute an important adjunct for the treatment of chronic periodontitis in smokers. [ABSTRACT FROM AUTHOR]

Doxycycline (DXC) is a broad-spectrum antibacterial antimicrobial administered to horses for the treatment of bacterial infections which may also affect donkeys. Donkeys have a different metabolism than horses, leading to differences in the pharmacokinetics of drugs compared to horses. This study aimed to describe the population pharmacokinetics of DXC in donkeys. Five doses of DXC hyclate (10 mg/kg) were administered via a nasogastric tube, q12 h, to eight non-fasted, healthy, adult jennies. Serum, urine, synovial fluid and endometrium were collected for 72 h following the first administration. Doxycycline concentration was measured by competitive enzyme immunoassay. Serum concentrations versus time data were fitted simultaneously using the stochastic approximation expectation-maximization algorithm for nonlinear mixed effects. A one-compartment model with linear elimination and first-order absorption after intragastric administration, best described the available pharmacokinetic data. Final parameter estimates indicate that DXC has a high volume of distribution (108 L/kg) as well as high absorption (10.3 h−1) in donkeys. However, results suggest that oral DXC at 10 mg/kg q12 h in donkeys would not result in a therapeutic concentration in serum, urine, synovial fluid or endometrium by comparison to the minimum inhibitory concentration of common equine pathogens. Further studies are recommended to identify appropriate dosage and dosing intervals of oral DXC in donkeys.

Purpose: To formulate novel topical antibacterial gel containing Doxycycline Hyclate, Tea tree oil and Neem oil to evaluate their antibacterial activity. Methods: Formulation excipients were selected using Drug-excipients compatibility study. Prepared gel was subjected to various evaluation parameters like pH, viscosity, spreadability, homogeneity, drug content uniformity, in-vitro drug diffusion and antibacterial activity. Results: Prepared topical gel of doxycycline Hyclate was shown pH range 5.3±0.010 to 6.7±0.015, viscosity range 386±28.70 to 680±50.40 cp, spreadability range 18.14±0.98 to 28.13±2.18 g.cm/s and homogeneous. Prepared gel was shown uniformity in drug content which ranges from 94.41±0.61 to 97.44±0.69%, zone of inhibition ranges 13.66±1.69 to 32.00±1.63 mm for Staphylococcus aureus, 04.00±1.63 to 12.33±0.94 mm for Pseudomonas aeruginosa and 11.66±0.94 to 33.33±1.24 mm for Propionibacterium acne . Prepared gel formulations were shown the negligible amount of drug diffusion, not more than 3.22±0.04% was shown the non-fickian type of diffusion through the egg membrane. Conclusion: Formulation F8 was shown better antibacterial activity as compared to its other formulations. As the concentration of neem oil and tea tree oil was increased from 0.5 to 3% and 0.5 to 2% respectively in the gel, antibacterial activity was synergistically improved against Staphylococcus aureous, Pseudomonas aeruginosa and Propionibacterium acne . The prepared gel formulation was found useful for topical application due to its negligible diffusion, good spreadability, neutral pH, low viscosity and no irritation on human skin. [ABSTRACT FROM AUTHOR]

• The removal efficiency of doxycycline hyclate was achievable in the range of 98.5–99.4% at pH 6.03–8.02 and current intensity of 5.39 mA cm−2. • Sodium chloride, as a supporting electrolyte, promoted high removal of doxycycline hyclate than sodium nitrate and potassium chloride. • For the same removal efficiency of doxycycline hyclate, time was inversely proportional to the inter-electrode distance. • The chemical nature of sorption between doxycycline hyclate and aluminium flocs, as bayerite was corroborated. Electrochemical treatment involving a coupled coagulation and floatation was performed in the removal of doxycycline hyclate (DCH) from aqueous solutions. All the experiments were carried out in an electrochemical reactor of 1.5 L which contained aluminum electrodes as cathode and anode. The removal of doxycycline hyclate (DCH) species by EC/EF was determined as a function of electrolysis time, pH, current intensity, flow rate and DCH concentration. From the observed results, it was corroborated that the DCH removal through the EC/EF process was excellent. The effective contribution from initial pH (7.03) and current intensity (5.39 mA cm−2) was very much remarkable and well apparent from flocs of good buoyancy. The removal of DCH was inversely proportional to spacing between electrodes (SBE) and circulating flow rate in the presence of the supporting NaCl electrolyte of 1 g L−1. It was also highly promoted by the addition of NaCl in comparison with NaNO 3 and KCl to the electrolytic system. The compliance of four kinetic models was verified with DCH removal system. The free energy values from DKR model suggested the nature of bonding by chemical forces. Characterization by FTIR, SEM and XRD interpreted the assignments of various functional groups, surface morphology and crystalline incorporated amorphous nature, respectively of electro-generated flocs. The current efficiency and specific electrical energy consumption at optimized conditions of the EC/EF system were calculated. [ABSTRACT FROM AUTHOR]

To minimize the gastric and esophageal injury effect, a system to deliver doxycycline hyclate (DOXY) to the duodenum area is needed. DOXY‐containing modified‐release oral pellets (DMOP) coated with hydroxypropyl methylcellulose phthalate HP‐55 (HPMCP HP‐55) and hydroxypropyl methylcellulose E15 (HPMC E15) appear to be a reasonable choice. This coating layer dissolves at pH 5.5, which is the pH of the duodenum, but not at a gastric pH (1.2). The formulation and preparation of DMOP were optimized, and a scale‐up test was performed. The results showed that the production reproducibility was acceptable, and the quality of DMOP well met the standards of Chinese Pharmacopeia (Ch.P, 2015 edition). Notably, the accumulated DOXY release was lower than 50% at pH 1.2 (20 min) and higher than 85% at pH 5.5, which met the USP40‐NF35 standard for DOXY modified‐release formulations. Moreover, the storage stability of DMOP with different packages was investigated by stress testing, accelerated and long‐term testings. The stability of DMOP was maintained up to 12 months, in terms of DOXY content and in vitro release behavior. The results seem to suggest that DMOP could be a promising duodenum delivery system. [ABSTRACT FROM AUTHOR]

The adsorption of doxycycline hyclate on the low-cost adsorbent cobalt oxide was carried out, in a thermostated shaker at three different temperatures (40 °C, 50 °C and 60 °C), and studied other parameters were effected on the adsorption process including initial concentration, a weight of cobalt oxide and effect of pH. The high value of coefficient of determination of 0.985 and low value for Chi-square test of 0.346 for Langmuir linear equation at the temperature of 40 °C are referred to a good accuracy and agreement for the method. Also it was observed that the Freundlich linear equation showed the high value of coefficient of determination of 0.914 and low value of Chi-square test of 0.679 at the same temperature, and it can be realized that the Freundlich linear isotherm provided better agreement with the Langmuir linear isotherm at the temperature of 40 °C. Moreover, the negative values of the Gibbs free energy and the positive value of the enthalpy indicated spontaneity and exothermic nature of the adsorption process. [ABSTRACT FROM AUTHOR]

• GO and doxycycline was co-immobilized on TiO₂ via tyrosinase-mediated reaction. • GO was functioned as both antimicrobial agent and drug carrier. • The release of doxycycline from surface was sustained and controlled for 30 days. • The immobilized surfaces showed excellent antimicrobial effect without cytotoxicity. Preventing implant-associated infection, which can lead to implant failure and increased medical costs, is one of the biggest challenges in the orthopaedic surgeons. Therefore, the development of stable and highly effective surface modifications to increase the antimicrobial properties of implants is required. In this study, graphene oxide (GO-)-immobilized titanium dioxide (TiO₂) was developed to efficiently carry and release antimicrobial drugs. Firstly, tyramine-conjugated GO (GOTA) was synthesized and immobilized onto the surfaces of TiO₂ through tyrosinase (Tyr)-catalyzed oxidative reaction (GOTA/TiO₂). Doxycycline hyclate (Dox) was then loaded onto GOTA/TiO₂ via non-covalent interactions between GO and Dox (Dox/GOTA/TiO₂), including electrostatic interaction, π-π stacking, hydrophobic interaction, and hydrogen bonds. The amount of loaded drug was able to be controlled, reaching a maximum of 36 μg/cm2. in vitro experiments revealed that the sustained release of Dox from the TiO₂ surfaces continued for over 30 days. Compared with bare TiO₂ and GOTA/TiO 2 , Dox/GOTA/TiO₂ exhibited superior antibacterial activity against both gram-negative Escherichia coli and gram-positive Staphylococcus aureus bacteria, without affecting the viability of human dermal fibroblasts. The obtained results indicated that GO-immobilized TiO₂ is an effective carrier for antimicrobial drug delivery to reduce implant-associated infection through the synergistic antimicrobial effect of GO and the prescribed drugs. [ABSTRACT FROM AUTHOR]

Doxycycline hyclate (DX)-loaded bleached shellac (BS) in situ forming gel (isg) and in situ microparticle (ism) were prepared using dimethyl sulfoxide (DMSO), N -methyl pyrrolidone (NMP) and 2-pyrrolidone (PYR) as solvents. Solvent and drug release characteristics of them were investigated. Diffusion rate of solvent applied in formulation was as following: DMSO > NMP > PYR. In situ forming systems comprising PYR had the slowest release rate of solvent and drug while water flowed into system in rank of solvent order as following: DMSO > NMP > PYR. Size and density of pores were increased by time similarly to release rate of solvent and drug. At steady state, total mass loss converted to PYR ≫ NMP > DMSO similarly to water content pattern. The solvent and DX release from ism were apparently slower than those from isg owing to barrier effect from oil component. The isg and ism prepared from DMSO exhibited the highly sponge-like structure than that using PYR which the later matrices eventually dissipated due to hydrolysis of BS which was accelerated by PYR-induced water accumulation. PYR was the most appropriated solvent for BS isg and ism because their formulations demonstrated the proper sustained drug release and preferable self-degradation. [ABSTRACT FROM AUTHOR]