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Cholera, caused by Vibrio cholerae, is a severe diarrheal disease that necessitates prompt diagnosis and effective treatment. This review comprehensively examines various diagnostic methods, from traditional microscopy and culture to advanced nucleic acid testing like polymerase spiral reaction and rapid diagnostic tests, highlighting their advantages and limitations. Additionally, we explore evolving treatment strategies, with a focus on the challenges posed by antibiotic resistance due to the activation of the SOS response pathway in V. cholerae. We discuss promising alternative treatments, including low-pressure plasma sterilization, bacteriophages, and selenium nanoparticles. The paper emphasizes the importance of multidisciplinary approaches combining novel diagnostics and treatments in managing and preventing cholera, a persistent global health challenge. The current re-emergent 7th pandemic of cholera commenced in 1961 and shows no signs of abeyance. This is probably due to the changing genetic profile of V. cholerae concerning bacterial pathogenic toxins. Given this factor, we argue that the disease is effectively re-emergent, particularly in Eastern Mediterranean countries such as Lebanon, Syria, etc. This review considers the history of the current pandemic, the genetics of the causal agent, and current treatment regimes. In conclusion, cholera remains a significant global health challenge that requires prompt diagnosis and effective treatment. Understanding the history, genetics, and current treatments is crucial in effectively addressing this persistent and re-emergent disease.
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Bacteriófagos , Cólera , Vibrio cholerae , Humanos , Cólera/diagnóstico , Cólera/epidemiologia , Cólera/prevenção & controle , Vibrio cholerae/genética , Bacteriófagos/fisiologia , Filogenia , Toxina da Cólera/genética , Toxina da Cólera/metabolismoRESUMO
Olive leaves were utilized to produce activated biomass for the removal of ciprofloxacin (CIP) from water. The raw biomass (ROLB) was activated with sodium hydroxide, phosphoric acid, and Dead Sea water to create co-precipitated adsorbent (COLB) with improved adsorption performance. The characteristics of the ROLB and COLB were examined using SEM images, BET surface area analyzer, and ATR-FTIR spectroscopy. COLB has a BET surface area of 7.763 m2/g, markedly higher than ROLB's 2.8 m2/g, indicating a substantial increase in adsorption sites. Through investigations on operational parameters, the optimal adsorption efficiency was achieved by COLB is 77.9% within 60 min, obtained at pH 6, and CIP concentration of 2 mg/mL. Isotherm studies indicated that both Langmuir and Freundlich models fit the adsorption data well for CIP onto ROLB and COLB, with R2 values exceeding 0.95, suggesting effective monolayer and heterogeneous surface adsorption. The Langmuir model revealed maximum adsorption capacities of 636 mg/g for ROLB and 1243 mg/g for COLB, highlighting COLB's superior adsorption capability attributed to its enhanced surface characteristics post-modification. Kinetic data fitting the pseudo-second-order model with R2 of 0.99 for ROLB and 1 for COLB, along with a higher calculated qe for COLB, suggest its modified surface provides more effective binding sites for CIP, enhancing adsorption capacity. Thermodynamic analysis revealed that the adsorption process is spontaneous (∆Go < 0), and exothermic (∆Ho < 0), and exhibits a decrease in randomness (∆So < 0) as the process progresses. The ΔH° value of 10.6 kJ/mol for ROLB signifies physisorption, whereas 35.97 kJ/mol for COLB implies that CIP adsorption on COLB occurs through a mixed physicochemical process.
Assuntos
Biomassa , Ciprofloxacina , Olea , Folhas de Planta , Termodinâmica , Poluentes Químicos da Água , Olea/química , Adsorção , Ciprofloxacina/química , Cinética , Poluentes Químicos da Água/química , Folhas de Planta/química , Purificação da Água/métodosRESUMO
Deep eutectic solvents (DESs) and ionic liquids (ILs) offer novel opportunities for several pharmaceutical applications. Their tunable properties offer control over their design and applications. Choline chloride (CC)-based DESs (referred to as Type III eutectics) offer superior advantages for various pharmaceutical and therapeutic applications. Here, CC-based DESs of tadalafil (TDF), a selective phosphodiesterase type 5 (PDE-5) enzyme inhibitor, were designed for implementation in wound healing. The adopted approach provides formulations for the topical application of TDF, hence avoiding systemic exposure. To this end, the DESs were chosen based on their suitability for topical application. Then, DES formulations of TDF were prepared, yielding a tremendous increase in the equilibrium solubility of TDF. Lidocaine (LDC) was included in the formulation with TDF to provide a local anaesthetic effect, forming F01. The addition of propylene glycol (PG) to the formulation was attempted to reduce the viscosity, forming F02. The formulations were fully characterised using NMR, FTIR and DCS techniques. According to the obtained characterisation results, the drugs were soluble in the DES with no detectable degradation. Our results demonstrated the utility of F01 in wound healing in vivo using cut wound and burn wound models. Significant retraction of the cut wound area was observed within three weeks of the application of F01 when compared with DES. Furthermore, the utilisation of F01 resulted in less scarring of the burn wounds than any other group including the positive control, thus rendering it a candidate formula for burn dressing formulations. We demonstrated that the slower healing process associated with F01 resulted in less scarring potential. Lastly, the antimicrobial activity of the DES formulations was demonstrated against a panel of fungi and bacterial strains, thus providing a unique wound healing process via simultaneous prevention of wound infection. In conclusion, this work presents the design and application of a topical vehicle for TDF with novel biomedical applications.
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Anti-Infecciosos , Queimaduras , Líquidos Iônicos , Anti-Infecciosos/farmacologia , Colina/química , Cicatriz , Líquidos Iônicos/química , Preparações Farmacêuticas , Inibidores da Fosfodiesterase 5/farmacologia , Solventes/química , Tadalafila/farmacologia , Cicatrização , AnimaisRESUMO
The current work was aimed at the development of a topical drug delivery system for azelaic acid (AzA) for acne treatment. The systems tested for this purpose were deep eutectic systems (DESs) prepared from choline chloride (CC), malonic acid (MA), and PEG 400. Three CC to MA and eight different MA: CC: PEG400 ratios were tested. The physical appearance of the tested formulations ranged from solid and liquid to semisolid. Only those that showed liquid formulations of suitable viscosity were considered for further investigations. A eutectic mixture made from MA: CC: PEG400 1:1:6 (MCP 116) showed the best characteristics in terms of viscosity, contact angle, spreadability, partition coefficient, and in vitro diffusion. Moreover, the MCP116 showed close rheological properties to the commercially available market lead acne treatment product (Skinorin®). In addition, the formula showed synergistic antibacterial activity between the MA moiety of the DES and the AzA. In vitro diffusion studies using polyamide membranes demonstrated superior diffusion of MCP116 over the pure drug and the commercial product. No signs of skin irritation and edema were observed when MCP116 was applied to rabbit skin. Additionally, the MCP116 was found to be, physically and chemically, highly stable at 4, 25, and 40 °C for a one-month stability study.
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Acne Vulgar , Fármacos Dermatológicos , Animais , Coelhos , Ácidos Dicarboxílicos/química , Fármacos Dermatológicos/uso terapêutico , Pele , Preparações Farmacêuticas , Colina/química , Acne Vulgar/tratamento farmacológico , Solventes/químicaRESUMO
Fatty acids, including medium-chain saturated and polyunsaturated fatty acids, are known for their broad health benefits, including antimicrobial activity. Through their green properties, deep eutectic systems have been heralded as having the potential to be at the forefront of pharmaceutical applications. In this work, capric acid and geranic acid, two examples of medium-chain saturated and polyunsaturated fatty acids, were employed to enhance the pharmaceutical properties and the antibacterial activity of levofloxacin. To this end, levofloxacin formulations with either capric or geranic acid were prepared and characterized using appropriate techniques. Levofloxacin was utilized to create innovative deep eutectic systems in conjunction with capric acid at three different molar ratios: 1:9, 2:8 and 3:7. This was confirmed through a rigorous analysis involving nuclear magnetic resonance, infrared spectroscopy and differential scanning calorimetry. Furthermore, it is noteworthy that geranic acid demonstrated an impressive threefold improvement in levofloxacin's solubility compared to its solubility in aqueous solutions. The antibacterial activity of the novel combinations of levofloxacin with either fatty acid was evaluated using a checkerboard titration assay. Gratifyingly, both formulations exhibited synergistic effects against a panel of levofloxacin-sensitive and resistant Gram-negative bacteria. In conclusion, the observed superior antibacterial activity of levofloxacin illuminates the potential use of fatty acid-based formulations and deep eutectic systems as green and innovative strategies to combat the global antimicrobial resistance problem.
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Ácidos Graxos , Levofloxacino , Levofloxacino/farmacologia , Ácidos Graxos/farmacologia , Ácidos Graxos/química , Antibacterianos/farmacologia , Ácidos Decanoicos , Ácidos Graxos Insaturados , Preparações Farmacêuticas , Solventes/químicaRESUMO
Chitosan is an abundant organic polysaccharide, which can be relatively easily obtained by chemical modification of animal or fungal source materials. Chitosan and its derivatives have been shown to exhibit direct antiviral activity, to be useful vaccine adjuvants and to have potential anti-SARS-CoV-2 activity. This thorough and timely review looks at the recent history of investigations into the role of chitosan and its derivatives as an antiviral agent and proposes a future application in the treatment of endemic SARS-CoV-2.
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COVID-19 , Quitosana , Adjuvantes de Vacinas , Animais , Antivirais/farmacologia , Quitosana/farmacologia , Humanos , SARS-CoV-2RESUMO
A new composite film from chitosan (CS) and biotin (BIO) was developed to enhance burn wound healing. The film was prepared by electrostatic interaction between CS and BIO. Four different ratios of CS to BIO v/v (4:1, 3:2, 2:3, and 1:4) were prepared. The films were comprehensively characterized using FTIR, DSC, and AFM. The in-vitro release studies showed that the most promising formula with the highest release behavior was CS to BIO 1: 4. The ex vivo adhesion times were reported as 0.50 ± 0.30 min for CS film compared to 6.2 ± 0.30, 8.4 ± 0.40, 11.2 ± 0.50, and 13.83 ± 1.04 min for CS to BIO films v/v (1:4, 2:3, 3:2 and 4:1), respectively. Most importantly, the skin healing activities of CS/BIO film in the excision wound model in mice and skin burn model in rats showed faster rates of healing compared to CS and placebo. Furthermore, skin stretching and burn wound contraction behavior treated with CS/BIO were higher than that of CS treated skin. In conclusion, the results obtained revealed that CS/BIO films possessed superior burn wound healing activity compared to CS.
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Queimaduras , Quitosana , Animais , Biotina/uso terapêutico , Queimaduras/tratamento farmacológico , Camundongos , Ratos , Pele , CicatrizaçãoRESUMO
Telmisartan (TLM) is a potent antihypertensive drug with pH-dependent aqueous solubility. This work aimed to enhance the solubility and dissolution rate of TLM by the co-amorphous drug amino acid (AA) approach by combining TLM, with different types and ratios of AAs. The co-amorphous TLM-AA blends were prepared by freeze-drying and investigated for solid-state characteristics like the dissolution rate enhancement of TLM. Among the prepared co-amorphous formulations, TLM-arginine (ARG) exhibited the greatest enhancement in solubility with increasing the molar ratio of ARG. The TLM-ARG at 1:2 ratio showed about a 57-fold increase in solubility of TLM and the highest dissolution percentage in phosphate buffer (pH7.5) (100% in 20 minutes) compared to both crystalline TLM (20% in 60 min) and physical mixture. Powder XRD, DSC, FTIR analysis and SEM demonstrated the formation of amorphous form within the co-amorphous formulations. Only TLM:ARG (1:0.5) were stable at (40°C, 75% RH) for a minimum of 90 days. In conclusion, ARG was able to stabilize the amorphous form of TLM and enhances its aqueous solubility and dissolution. The 1:2 w/w ratio of TLM-ARG co-amorphous showed the best solubility and dissolution rate while the 1:0.5 w/w ratio showed the best stability.
Assuntos
Aminoácidos/química , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Telmisartan/administração & dosagem , Bloqueadores do Receptor Tipo 1 de Angiotensina II/química , Soluções Tampão , Varredura Diferencial de Calorimetria , Composição de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Solubilidade , Telmisartan/química , Difração de Raios XRESUMO
This paper reports for the first time the possible formation of a novel room temperature therapeutic deep eutectic solvent (THEDES) of risperidone (RIS) with some fatty acids, namely capric acid (C10; CA), lauric acid (C12; LA), and myristic acid (C14; MA). All mixtures of RIS and MA yielded a solid or pasty-like solid and were readily discarded. Some of the prepared THEDESs from RIS and CA or LA have spontaneously transformed into a transparent liquid, without any precipitate at room temperature by simple physical mixing of the components. From the DSC thermograms, phase diagrams of the eutectic systems were constructed and the lowest obtained melting point for a RIS:CA mixture was 17°C at 40:60% w/w ratio. While 22°C was recorded as the lowest melting point for RIS:LA at a ratio of 30:70% w/w, solubility improvement of RIS was up to 70,000-fold compared with water. Freeze-drying microscopy provided valuable information regarding the phase change and transitions the drug undergoes as a function of temperature and it clarifies the interpretation of the DSC results and provides valuable evidence of drug crystals co-melting within the fatty acid base. The presence of natural fatty acid as one component of THEDES and the depression in the melting point significantly (P < 0.05) enhanced RIS skin permeation. Rheological studies showed a viscosity temperature dependency of the DES and well fitted to the Arrhenius equation. Application of the obtained THEDES on the shaved skin of rats revealed the absence of any irritation or edema effects.
Assuntos
Antipsicóticos/administração & dosagem , Risperidona/administração & dosagem , Administração Cutânea , Animais , Antipsicóticos/farmacocinética , Disponibilidade Biológica , Ratos , Risperidona/farmacocinética , Solubilidade , Solventes/química , Temperatura , Adesivo Transdérmico , ViscosidadeRESUMO
The combined properties of SepineoP 600 (S600), a self-gelling dispersion and SepineoSE 68 (M68), a natural liquid crystal forming surfactant, were utilized in the development of emulgel base for topical application. The emulgels were prepared in water alone or combined with propylene glycol (PG), polyethylene glycol 400 (PEG400) and glycerol (G) as cosolvents. Emulgels were characterized for their optical and flow behavior. Two model drugs: caffeine (CF) and methylparaben (MP) were used in the evaluation of drug permeation across the stratum corneum (SC). The results showed that emulgel prepared using 70% PG:water (1:1) and 30% S600 has the best flow behavior compared to other cosolvents. Also the permeability coefficient of CF was found to be higher than that of MP and the addition of 3% M68 improved the physical stability of the emulgel, but it did not affect the drug diffusion profile.
Assuntos
Absorção Cutânea/fisiologia , Solventes/química , Solventes/metabolismo , Tensoativos/química , Tensoativos/metabolismo , Fenômenos Químicos/efeitos dos fármacos , Química Farmacêutica , Feminino , Géis , Humanos , Técnicas de Cultura de Órgãos , Absorção Cutânea/efeitos dos fármacos , Solventes/farmacologia , Tensoativos/farmacologiaRESUMO
A dual stimuli-responsive nanocarrier was developed from smart biocompatible chitosan and soluplus graft copolymers. The copolymerization was investigated by differential scanning calorimetry (DSC), thermo-gravimetric analysis (TGA), and Fourier transform infrared (FTIR). The optimized chitosan-soluplus nanoparticles (CS-SP NPs) were further used for the encapsulation of a poorly water-soluble anticancer drug. Tamoxifen citrate (TC) was used as the model drug and it was loaded in CS-SP NPs. TC CS-SP NPs were characterized in terms of particle size, zeta potential, polydispersity, morphology, encapsulation efficiency, and physical stability. The nanoparticles showed homogenous spherical features with a size around 94 nm, a slightly positive zeta potential, and an encapsulation efficiency around 96.66%. Dynamic light scattering (DLS), in vitro drug release, and cytotoxicity confirmed that the created nano-system is smart and exhibits pH and temperature-responsive behavior. In vitro cellular uptake was evaluated by flow cytometry and confocal microscopy. The nanoparticles revealed a triggered increase in size upon reaching the lower critical solution temperature of SP, with 70% of drug release at acidic pH and 40 °C within the first hour and a 3.5-fold increase in cytotoxicity against MCF7 cells incubated at 40 °C. The cellular uptake study manifested that the prepared nanoparticles succeeded in delivering drug molecules to MCF7 and MDA-MB-231 cells. In summary, the distinctive characteristics provided by these novel CS-SP NPs result in a promising nano-platform for effective drug delivery in cancer treatment.
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Therapeutic deep eutectic solvents (THEDSs) are the best exemplification of green alternative formulations of active pharmaceutical ingredients (APIs) that offer superlative properties of APIs. Previously, THEDESs of risperidone, fentanyl and levofloxacin with capric acid (CA) were developed by our group. These APIs share cyclic tertiary amine nuclei. Herein, DESs of two drugs bearing cyclic tertiary amine nucleus, namely, droperidol and aripiprazole, in the presence of CA, were investigated as model drugs. Comprehensive analyses were conducted using liquid-state 1D and 2D NMR and differential scanning calorimetry (DSC) to elucidate the regiochemistry and thermodynamic mechanisms bringing about those THEDESs. Everted gut sac technique was used to study the flux of the developed THEDESs. 1D and 2D NMR techniques analyses revealed the importance of cyclic tertiary amine nuclei in forming interactions with CA. This was confirmed by the downfield shift of the protons proximal to the tertiary amine groups compared to the individual drugs. Diffusion NMR analysis (DOSY) showed a significant reduction in the diffusion coefficient of CA in the mixed system compared with CA in isolation. Thermal analysis of the two drugs revealed that the drugs have a low tendency to recrystallise upon melting but rather vitrify from a melt to form an amorphous solid. Interestingly, the superior absorption and flux of the THEDES formulation of droperidol was demonstrated using the ERIS. Collectively, this work provides a green method to attain liquid formulations of APIs with enhanced pharmacokinetic features.
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Aim: The aim was to evaluate drug-plasma binding (DPB).by employing Hollow Fiber-in-Syringe Equilibrium Sampling Through Supported Liquid Membrane (HFiS ESTSLM) and RP-HPLC analysis. Materials & methods: HFiS ESTSLM and RP-HPLC were used to evaluate DPB of three weak basic drugs (Metoprolol, Diphenhydramine, and Sildenafil) with differing hydrophilicity and binding ability to blood plasma. Results: The results exhibited an increasing drug-dependent magnitude of DPB for the three model drugs. This trend of DPB confirmed that HFiS ESTSLM has the required sensitivity for determining DPB of the drugs. The DPB was drug concentration-dependent within the tested drug concentration range, especially at high concentration. Conclusion: HFiS ESTSLM and RP-HPLC offered a simple, easy and cost-effective procedure to evaluate DPB of these basic drugs.
[Box: see text].
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Monoclonal antibodies (mAbs) have revolutionised the biopharmaceutical market. Being proteinaceous, mAbs are prone to chemical and physical instabilities. Various approaches were attempted to stabilise proteins against degradation factors. Ionic liquids (ILs) and deep eutectic solvents (DESs) have been established as green solvents for ever-increasing pharmaceutical and biopharmaceutical applications. Hence, amino acid (AA)-based ILs, were used for the first time, for mAb stabilisation. Choline (Ch)-based DESs were also utilised for comparison purposes. The prepared ILs and DESs were utilised to stabilise Atezolizumab (Amab, anti-PDL-1 mAb). The formulations of Amab in ILs and DESs were incubated at room temperature, 45 or 55 °C. Following this, the structural stability of Amab was appraised. Interestingly, Ch-Valine retained favourable structural stability of Amab with minimal detected aggregation or degradation as confirmed by UV-visible spectroscopy and protein Mass Spectroscopy. The measured hydrodynamic diameter of Amab in Ch-Valine ranged from 10.40 to 11.65 nm. More interestingly, the anticancer activity of Amab was evaluated, and Ch-Valine was found to be optimum in retaining the activity of Amab when compared to other formulations, including the control Amab sample. Collectively, this study has spotlighted the advantages of adopting the Ch-AA ILs for the structural and functional stabilising of mAbs.
Assuntos
Aminoácidos , Anticorpos Monoclonais Humanizados , Antineoplásicos , Líquidos Iônicos , Líquidos Iônicos/química , Anticorpos Monoclonais Humanizados/química , Anticorpos Monoclonais Humanizados/farmacologia , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia , Aminoácidos/química , Coloides/química , Estabilidade de Medicamentos , Anticorpos Monoclonais/química , Anticorpos Monoclonais/farmacologia , Estabilidade Proteica , Temperatura , Linhagem Celular Tumoral , Solventes/químicaRESUMO
The complex relationship between probiotics and human health goes beyond their traditional function in gut health, generating considerable interest for their broad potential in disease treatment. This review explores the various functions of probiotics, highlighting their impact on the immune system, their benefits for gut and oral health, their effects on metabolic and neurological disorders, and their emerging potential in cancer therapy. We give significant importance to studying the effects of probiotics on the gut-brain axis, revealing new and non-invasive therapeutic approaches for complex neurological disorders. In addition, we expand the discussion to encompass the impact of probiotics on the gut-liver and gut-lung axes, recognizing their systemic effects and potential in treating respiratory and hepatic conditions. The use of probiotic "cocktails" to improve cancer immunotherapy outcomes indicates a revolutionary approach to oncological treatments. The review explores the specific benefits associated with various strains and the genetic mechanisms that underlie them. This study sets the stage for precision medicine, where probiotic treatments can be tailored to meet the unique needs of each patient. Recent developments in delivery technologies, including microencapsulation and nanotechnology, hold great potential for enhancing the effectiveness and accuracy of probiotic applications in therapeutic settings. This study provides a strong basis for future scientific research and clinical use, promoting the incorporation of probiotics into treatment plans for a wide range of diseases. This expands our understanding of the potential benefits of probiotics in modern medicine.
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In the present systematic study, a sustained release of terbutaline sulfate tablet (TBS) was developed and optimized by employing the hydrophilic polymers; chitosan and xanthan gum mixed with sodium bicarbonate as a release modifying agent. This formulation was developed using direct compression technology. In vitro release studies indicated rapid swelling and drug release in the initial period of the acid stage from a matrix composed of chitosan and xanthan gum solely. Addition of sodium bicarbonate to the matrix resulted in sustained drug release. Various formulation factors such as polymer to polymer ratio, polymer viscosity and particle size were altered and their effect on dissolution pattern was illustrated. Manufacturing variables such as compression force and lubricant percentage were investigated and found not to influence the drug release profile of the resulted tablets. The release mechanism follows Korsmeyer-Peppas equation with n value indicating non-Fickian diffusion. The release profiles were analyzed using statistical method (one-way ANOVA) and f2 metric values and found to be similar to the commercial product Bricanyl(®). Reproducible data were obtained when scale-up of the formulation was performed.
Assuntos
Polímeros/química , Bicarbonato de Sódio/química , Terbutalina/química , Química Farmacêutica/métodos , Quitosana/química , Preparações de Ação Retardada , Difusão , Composição de Medicamentos/métodos , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Polissacarídeos Bacterianos/química , Solubilidade , Comprimidos/químicaRESUMO
In this work, the swelling and disintegration of drug-free sodium alginate (SA) compacts and the release of metformin HCl from SA matrix tablets were investigated in acidic media of different ethanol concentrations (0, 10, 20, and 40 % v/v), pH (1.2 and 4.5) and HPMC K4M concentrations (0-1 % w/v). The investigated dissolution media represented the consumption of different alcoholic beverages, the pH of fasted and fed states, and a range of viscosity resembling diluted homogenized FDA meal. The dissolution efficiency and the time to 50 % release (t50%) were selected as release parameters. It was found that both ethanol concentration and medium pH affected drug release from SA matrix tablets and the swelling of SA compacts. Dose dumping occurred at high ethanol concentration (40 %) at both media pH with almost complete drug release within 15-30 min associated with rapid matrix disintegration. HPMC at 0.5-1 % concentrations increased the medium's viscosity, preventing dose dumping at high ethanol concentrations. Erosion and disintegration of SA compacts were decelerated by increasing HPMC concentration in hydroethanolic media in consonance with decreased release rate from matrix tablets. ANOVA tests showed significant effects of pH and concentrations of ethanol and HPMC in the dissolution medium on the release parameters.
Assuntos
Alginatos , Etanol , Solubilidade , Viscosidade , Comprimidos , Concentração de Íons de Hidrogênio , Preparações de Ação Retardada , Derivados da HipromeloseRESUMO
The choice of optimum composition of a mixture of binary and ternary excipients for optimum compressional properties was investigated in this work. Excipients were chosen based on three types of excipients: plastic, elastic, and brittle fracture. Mixture compositions were selected based on a one-factor experimental design using the response surface methodology technique. Compressive properties comprising Heckel and Kawakita parameters, work of compression, and tablet hardness were measured as the main responses of this design. The one-factor RSM analysis revealed that there exist specific mass fractions that are associated with optimum responses for binary mixtures. Furthermore, the RSM analysis of the 'mixture' design type for the three components revealed a region of optimal responses around a specific composition. The foregoing had a mass ratio of 80:15:5 for microcrystalline cellulose: starch: magnesium silicate, respectively. Upon comparison using all RSM data, ternary mixtures were found to perform better in compression and tableting properties than binary mixtures. Finally, the finding of an optimal mixture composition has proven effective in its applicability in the context of the dissolution of model drugs (metronidazole and paracetamol).
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Olive farming is one of the key agricultural activities in Jordan, where nearly 70% of the cultivated land in Jordan is covered with olive trees. Olive harvesting generates massive quantities of agricultural waste which will be an environmental burden if not managed properly. The present study introduces the use of novel co-processed biomass extracted from the olive tree leaves for the adsorption of lead from contaminated water. Several biomass co-processing techniques using different concentrations of sodium hydroxide, phosphoric acid, and the Dead Sea water were investigated and their effect on the removal efficiency was demonstrated. Moreover, the effect of several parameters on the adsorption efficiency including biomass particle size, solution pH, contact time, adsorbent amount, and lead ion concentration was explored. It was inferred that biomass co-processing enhanced the adsorption capacity of lead. It was also found that the adsorption efficiency increased with decreasing biomass particle size due to the increase in surface area. The highest lead removal was attained at an efficiency value of 70% for the 0.1 mm particle size and at a maximum adsorption capacity recorded at pH 5. The foregoing had a negatively charged biomass surface which, as such, favored the cationic adsorption (pHPZC values around 2.8-4.5). For lead biosorption, the process was a rapid process whereby most adsorption was observed within the first 20 min. Concurrently, there were no considerable changes in lead removal thereafter. Theoretically, this was attributed to the decrease in the available adsorption sites on the biomass surface. On the other hand, a continuous increase in the removal efficiency was recorded upon increasing the adsorbent amount. However, there was a continuous decline in the removal efficiency upon an increase in the initial lead concentration. The experimental data were fitted well with Langmuir isotherm (indicating a monolayer adsorption isotherm), while kinetic data showed the best fit with a pseudo-second-order kinetic model.