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Aim: Insulin therapy require self-administration of subcutaneous injection leading to painful and inconvenient drug therapy. The aim is to fabricate nanoemulsion (NE) based insulin loaded microneedles with improved bioavailability and patient compliance. Materials & methods: Different ratios of polyvinyl alcohol and polyvinylpyrrolidone as polymers were prepared through micro-molding technique for microneedles. Characterization of were performed using scanning electron microscope, differential scanning calorimetry, Fourier-transform infrared spectroscopy and circular dichroism. Mechanical strength, hygroscopicity and pain perception of these microneedles were also evaluated. In vitro release, permeation and in vivo PK/PD study of NE-based microneedles were conducted. Results: NE-based microneedles of insulin have improved bioavailability and quick response. Conclusion: Microneedles loaded with insulin can be effectively delivered insulin transdermally to treat diabetes with increased convenience and patient compliance.
[Box: see text].
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This study aims to design and optimize ondansetron (OND) gastro-retentive floating minitablets for better and prolonged control of postoperative nausea and vomiting (PONV) with improved patient compliance. Minitablets were directly compressed and encapsulated in a size 2 capsule shell with an overall dose of 24 mg. Central composite design (CCD) was applied keeping one cellulose ether derivative HPMC K15M and Carbopol 971 as variable and used as swelling and rate retarding agents. The other cellulose derivative i.e. sodium carboxymethyl cellulose, along with mannitol, sodium bicarbonate, and talc, were used in fixed quantities. The floating lag time, total floating time, swelling index, in-vitro drug release, and zero-order (RSQ value), were critical quality parameters. The optimized formulation (Fpred) was evaluated for all critical parameters, along with surface morphology, thermal stability, chemical interaction, and accelerated stability. The in silico PBPK modeling was applied to compare the bioavailability of Fpred with reference OND immediate-release tablets. The numerical optimization model predicted >90 % drug release with zero-order at 12 h. In silico PBPK modeling revealed comparable relative bioavailability of Fpred with the reference formulation. The gastroretentive floating minitablets of OND were successfully designed for prolonged emesis control in patients receiving chemotherapeutic agents.
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BACKGROUND: Stroke is a neurological disease and a leading cause of mortality worldwide. Strokes mainly consist of two types: hemorrhage and ischemia. Stroke patients are being administered multiple drug therapy and are at risk of drug-related problems. AIM: To estimate drug-related problems (DRPs) and clinical end outcomes in hospitalized stroke patients. METHODS: Current study was a multicenter, cross-sectional prospective observational study including 250 stroke patients admitted to tertiary care hospitals in Karachi, Pakistan. The study included all clinical subtypes of stroke patients i.e. Stroke, Ischemic stroke, Hemorrhagic stroke, CVA, and TIA. Associations among patient-clinical end outcomes and drug therapy-related variables like DRPs, mortality, and morbidity rates were estimated using Pearson's chi-squared test. Statistical analysis was done by using SPSS software, version 25. RESULTS: A total of 250 patients participated in this study suffering from different clinical subtypes of stroke i.e. Ischemic stroke, hemorrhagic stroke, TIA, and CVA, including 46% male and 54% female patients. The majority of patients' stay at the hospital was between 1-10 days. The overall mortality rate in stroke patients was 51%. HAIs were observed in 70% of patients, HAIs faced by patients were SAP, CAP, UTI, sepsis, and VAP. Drugs were assessed according to NEML i.e. access group antibiotics, watch group antibiotics, reserve group antibiotics, statins, antiepileptics, and proton pump inhibitors. Majorly ceftriaxone was administered to 79% of patients, piperacillin-tazobactam to 52%, and cefixime to 48%, whereas meropenem was administered to 42% of patients along with vancomycin to 39% of total patients. A high mortality rate was observed in the case of Klebsiella pneumoniae and Staphylococcus aureus i.e. 78% and in the case of streptococcus pneumoniae 61% mortality rate was observed. Due to the presence of DRPs and various other clinical factors like comorbidities, DDIs, HAIs, administration of potentially nephrotoxic drugs, and administration of antibiotics without having CST, hospitalized stroke patients faced many problems. CONCLUSION: This study helped determine DRPs along with various clinical factors affecting the clinical end outcomes of patients suffering from any clinical subtype of stroke. Due to the enhancement in the evidence of the incidence of DRPs in tertiary care hospitals, pharmacist-led drug therapy review by interfering with doctors and other medical professionals at the patient bed site is needed and should be done to avoid any negative end outcomes and serious issues related to DRPs.
Subject(s)
Cross Infection , Drug-Related Side Effects and Adverse Reactions , Hemorrhagic Stroke , Ischemic Attack, Transient , Ischemic Stroke , Stroke , Humans , Male , Female , Drug-Related Side Effects and Adverse Reactions/drug therapy , Ischemic Attack, Transient/drug therapy , Cross-Sectional Studies , Anti-Bacterial Agents/adverse effects , Stroke/drug therapy , Stroke/epidemiology , Pharmaceutical Preparations , Cross Infection/drug therapy , Ischemic Stroke/drug therapyABSTRACT
Meningitis is an important cause of morbidity and mortality in children and adults. Its treatment strategy varies with age and gender. To assess potential drug-related problems (PDRP) and clinical outcomes in bacterial meningitis patients, a multicenter, clinical, descriptive, cross-sectional prospective observational study in 120 patients admitted to different tertiary care hospitals in Karachi was conducted. It includes both males 48% and females 52% belonging from all age groups i.e. peadiatrics (01 to 12 years), adults (18 to 65 years), and geriatrics (66 to 75 years). Out of these 72 patients were admitted in the public sector and 48 patients were admitted in private sector hospitals. Nosocomial infections were developed in 41% of patients during their stay at the hospital. Potentially nephrotoxic drugs were administered to all BM patients, these drugs should be administered carefully. Majorly Ceftriaxone was administered to 86% of patients, Vancomycin 71%, and meropenem 73% whereas 68% of patients were administered piperacillin-tazobactam. Organisms involved as causative agents in the majority of patients are Neisseria meningitides, Pseudomonas aeruginosa and, Streptococcus pneumoniae. DRPs impacted patient clinical outcomes in presence of many other factors like comorbidities, DDIs, Nis, administration of potentially nephrotoxic drugs, and administration of watch group and reserve group antibiotics without having culture sensitivity test, even after having CST no principles of de-escalation for antibiotics were done, which is a very important factor for hospitalized patients having IV antibiotics. The mortality rate among BM patients was 66%. The majority of patients (87%) stay at the hospital was 1-10 days. The present study helped in the identification of DRPs along with some other factors affecting the clinical outcomes in patients suffering from bacterial meningitis. Healthcare professionals should receive awareness and education on the importance of CST before initiating antibiotic therapy. Pharmacist-led medication review is necessary and should be followed to avoid negative outcomes and serious consequences related to DRPs.
Subject(s)
Anti-Bacterial Agents , Meningitis, Bacterial , Adult , Child , Female , Humans , Male , Anti-Bacterial Agents/adverse effects , Cross-Sectional Studies , Meningitis, Bacterial/drug therapy , Tertiary Care Centers , Vancomycin/adverse effects , Infant, Newborn , Infant , Child, Preschool , Adolescent , Young Adult , Middle Aged , AgedABSTRACT
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has transformed the global view of education, including graduate and postgraduate education making the development of an alternative approach in times of social isolation an academic imperative. The present review aims to investigate the challenges experienced among undergraduate and postgraduate education and the strategies adopted to address these challenges during the pandemic. METHOD: The preferred reporting items for the systematic review and meta-analyses extension for Scoping Reviews (PRISMA-ScR) were followed. The aim was to include journal articles published in the English language that discussed the influence of the pandemic on educational processes and applied innovative approaches as a solution to educational challenges. From January to August 2020, PubMed, EMBASE, and Google Scholar were searched for articles, yielding 10,019 articles. Two groups of authors examined the retrieved articles separately to avoid any risk of bias. The title and abstract of the articles were used for scrutiny, followed by full-text screening based on the established inclusion and exclusion criteria. The facts and findings of the studies were also discussed based on per capita income, literacy rate, and Internet accessibility. RESULTS: Thirty of the obtained articles were included in the study. The selected articles were from North and South/Latin America, Asia & Pacific, South Africa, and Europe regions. Nineteen of the selected articles dealt with undergraduate education, ten with postgraduate, and one with both groups. The affordability of digital devices and the availability of Internet services were the major challenges for low- and middle-income economies. The ZOOM platform has been adopted by more than 90% of the education systems. CONCLUSION: Means of communication, including visual media, digitized content, and other web-based platforms, have been recognized as efficient learning and training tools, but have not been fully accessible for mass application and use due to the lack of availability of resources, their cost, and insufficient training among the users. In light of this review, it is suggested that harmonized and collaborative efforts should be made to develop cost-effective and user-friendly tools to overcome the current challenges and prevent future educational crises. SYSTEMIC REVIEW REGISTRATION: The review was not registered.
Subject(s)
COVID-19 , Humans , Communication , COVID-19/epidemiology , Learning , Pandemics , StudentsABSTRACT
A taste-masked chewable tablet of ciprofloxacin using ion exchange resin Kyron T-134 for enhancing compliance for the paediatric population was developed. The drug-to-resin ratio was optimized for maximum taste masking by studying the effects of soaking time (X1) and mixing time (X2) on complexation (%) using Central Composite Rotatable Design (CCRD). The resin complexes were characterized by bitterness score, DSC, FTIR, and PXRD. The complex was further formulated and optimized into chewable tablets through full factorial design, The optimized formulation was subjected to a bioequivalence study, and a virtual approach of PBPK modelling was adapted to predict the pharmacokinetics of the drug in the paediatric group. The drug resin ratio of 1:1.5 yielded an optimum drug loading of 99.05%. The optimized formulation shows minimum disintegration time with more than 99% drug release within 30 min. The formulation F-9 was found to be bioequivalent with a geometric mean ratio of Cmax, Tmax, AUC0-t, and AUC0-∞ within 90% CI. It was concluded that quality by design approach can successfully be applied to optimize the drug resin ratio and PBPK modeling is a successful predictive tool for estimating the pharmacokinetics of ciprofloxacin HCl in the paediatric population.
Subject(s)
Ciprofloxacin , Taste , Humans , Child , Therapeutic Equivalency , Drug Liberation , Resins, Plant , TabletsABSTRACT
This study investigated the ability of natural nanotubular clay mineral (Halloysite) and cellulose ether based biocomposite matrix as a controlled release agent for Verapamil HCl (BCS Class-I). Drug-loaded halloysite was prepared and tablet formulations were designed by varying amount of hydroxy propyl methyl cellulose (HPMC K4M). Physical characterization was carried out using SEM, FTIR, and DSC. Tabletability profiles were evaluated using USP1062 guidelines. Drug release kinetics were studied, and physiologically based pharmacokinetic (PBPK) modeling was performed. Compressed tablets possess satisfactory yield pressure of 625 MPa with adequate hardness and disintegration within 30 min. The initial release of the drug was due to surface drug on tablets, while the prolonged release at later time points (around 80 % drug release at 12 h) were due to halloysite loading. The FTIR spectra exhibited electrostatic attraction between the positively charged drug and the negatively charged Si-O-Si functional group of halloysite, while the thermogram showed Verapamil HCl melting point at ~146 °C with enthalpy change of -126.82 J/g. PBPK modeling exhibited PK parameters of optimized matrix formulation (VER-HNT3%) comparable to in vivo data. The study effectively demonstrated the potential of prepared biocomposite matrix as a commercially viable oral release modifying agent for highly soluble drugs.
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Carcinogenic colorectal hemorrhage can cause severe blood loss and longitudinal ulcer, which ultimately become fatal if left untreated. The present study was aimed to formulate targeted release gemcitabine (GC)-containing magnetic microspheres (MM) of halloysite nanotubes (MHMG), chitosan (MCMG), and their combination (MHCMG). The preparation of MM by magnetism was confirmed by vibrating sample magnetometry (VSM), the molecular arrangement of NH2, alumina, and silica groups was studied by X-ray diffraction (XRD) and energy-dispersive spectroscopy (EDS), the hollow spherical nature of the proposed MM was observed by scanning electron microscopy (SEM), functional groups were characterized by Fourier transform infrared (FTIR) spectroscopy and thermochemical modification was studied by thermogravimetric analysis (TGA). In vitro thrombus formation showed a decreasing trend of hemostatic time for MMs in the order of MHMG3 < MCMG3 < MHCMG7, which was confirmed by whole blood clotting kinetics. Interestingly, rat tail amputation and liver laceration showed 3 folds increased clotting efficiency of optimized MHCMG7 compared to that of control. In vivo histopathological studies and cell viability assays confirmed the regeneration of epithelial cells. The negligible systemic toxicity of MHCMG7, more than 90% entrapment of GC and high % release in alkaline medium made the proposed MM an excellent candidate for the control of hemorrhage in colorectal cancer. Conclusively, the healing of muscularis and improved recovery of the colon from granulomas ultimately improved the therapeutic effects of GC-containing MMs. The combination of both HNT and CTS microspheres made them more targeted.
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Introduction: A SeDeM expert tool-driven I-optimal mixture design has been used to develop a directly compressible multiparticulate based extended release minitablets for gastro-retentive drug delivery systems using loxoprofen sodium as a model drug. Methods: Powder blends were subjected to stress drug-excipient compatibility studies using FTIR, thermogravimetric analysis, and DSC. SeDeM diagram expert tool was utilized to assess the suitability of the drug and excipients for direct compression. The formulations were designed using an I-optimal mixture design with proportions of methocel K100M, ethocel 10P and NaHCO3 as variables. Powder was compressed into minitablets and encapsulated. After physicochemical evaluation lag-time, floating time, and drug release were studied. Heckel analysis for yield pressure and accelerated stability studies were performed as per ICH guidelines. The in silico PBPK Advanced Compartmental and Transit model of GastroPlus™ was used for predicting in vivo pharmacokinetic parameters. Results: Drug release follows first-order kinetics with fickian diffusion as the main mechanism for most of the formulations; however, a few formulations followed anomalous transport as the mechanism of drug release. The in-silico-based pharmacokinetic revealed relative bioavailability of 97.0%. Discussion: SeDeM expert system effectively used in QbD based development of encapsulated multiparticulates for once daily administration of loxoprofen sodium having predictable in-vivo bioavailability.
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The study is based on using SeDeM expert system in developing controlled-release tramadol HCl osmotic tablets and its in-silico physiologically based pharmacokinetic (PBPK) modeling for in-vivo pharmacokinetic evaluation. A Quality by Design (QbD) based approach in developing SeDEM-driven full factorial osmotic drug delivery was applied. A 24 Full-factorial design was used to make the trial formulations of tramadol HCl osmotic tablets using NaCl as osmogen, Methocel K4M as rate controlling polymer, and avicel pH 101 as diluent. The preformulation characteristics of formulations (F1-F16) were determined by applying SeDeM Expert Tool. The formulation was optimized followed by in-vivo predictive pharmacokinetic assessment using PBPK "ACAT" model of GastroPlus™. The FTIR results showed no interaction among the ingredients. The index of good compressibility (ICG) values of all trial formulation blends were ≥5, suggesting direct compression is the best-suited method. Formulation F3 and F4 were optimized based on drug release at 2, 10, and 16 h with a zero-order kinetic release (r 2 = 0.992 and 0.994). The SEM images confirmed micropores formation on the surface of the osmotic tablet after complete drug release. F3 and F4 were also stable (shelf life 29.41 and 23.46 months). The in vivo simulation of the pharmacokinetics of the PBPK in-silico model revealed excellent relative bioavailability of F3 and F4 with reference to tramadol HCl 50 mg IR formulations. The SeDeM expert tool was best utilized to evaluate the compression characteristics of selected formulation excipients and their blends for direct compression method in designing once-daily osmotically controlled-release tramadol HCl tablets. The in-silico GastroPlus™ PBPK modeling provided a thorough pharmacokinetic assessment of the optimized formulation as an alternative to tramadol HCl in vivo studies.
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Purpose: Halloysite nanotubes (HNTs) are a versatile and highly investigated clay mineral due to their natural availability, low cost, strong mechanical strength, biocompatibility, and binding properties. The present work explores its role for retarding and controlling the drug release from the composite polymer matrix material. Methods: For this purpose, nanocomposite films comprising propranolol HCl and different concentrations of HNTs were formulated using the "solution casting method". The menthol in a concentration of 1% w/v was used as a permeation enhancer, and its effect on release and permeation was also determined. Quality characteristics of the nanocomposite were determined, and in vitro release and permeation studies were performed using the Franz diffusion system. The data was analyzed using various mathematical models and permeation parameters. Optimized formulation was also subjected to skin irritation test, FTIR, DSC, and SEM study. Systemic absorption and disposition of propranolol HCl from the nanocomposites were predicted using the GastroPlus TCAT® model. Results: The control in drug release rate was associated with the higher concentration of HNTs. F8 released 50% of propranolol within 8 hours (drug, HNTs ratio, 1:2). The optimized formulation (F6) with drug: HNTs (2:1), exhibited drug release 80% in 4 hours, with maximum flux of 145.812 µg/cm2hr. The optimized formulation was found to be a non-irritant for skin with a shelf life of 35.46 months (28-30 â). The in silico model predicted Cmax, Tmax, AUCt , and AUCinf as 32.113 ng/mL, 16.58 h, 942.34 ng/mL×h, and 1102.9 ng/mL×h, respectively. Conclusion: The study demonstrated that HNTs could be effectively used as rate controlling agent in matrix type transdermal formulations.
Subject(s)
Drug Delivery Systems , Propranolol , Administration, Cutaneous , Clay , Computer Simulation , Drug LiberationABSTRACT
This study was conducted to determine the various socio-demographic, economic, and clinical variables (SDECVs) which influence the health-related quality of life (HRQoL) of hypertensive patients. Three hundred and fifty hypertensive patients participated in this study through a structured questionnaire and EQ 5D 5L. 211(60.28%) participants had stage 1, and 139 (39.7%) had stage 2 hypertension. No participants reported severe problems in any domain on EQ 5D 5L. Generalize Linear Model (GLM) was used to assess the association between HRQoL and SDECVs. The mean utility and VAS score was 0.64 (±0.15) and 63.17 (±11.01) respectively. The participants of the stage 1 hypertension group had a significantly better score on each domain of EQ 5D 5L as compared to stage 1 (0.027, 0.010, 0.00, 0.00, 0.048). No participant in either group reported extreme problems in any domain. Among socio-demographic factors, the males, non-smokers, income sharing, and healthy normal hypertensive patients had better HRQoL (0.009, 0.016, 0.019, and 0.003). A lower cost of treatment was also associated with better HRQoL (0.017). Among clinical variables, stage 1 hypertension had better HRQoL than stage 2(0.035). The number of prescribed antihypertensive drugs had no effect on the quality of life (0.253), however, the non-pharmacologic interventions such as reduction in salt and oil consumption (0.035), reduction in beverages consumption (0.0014) and increased water intake (0.010) had resulted in better QoL. The patients who reported dizziness had poor HRQoL while patients who had cardiac problems and diabetes reported a significantly lower EQ-VAS score. The effect of gender on the HRQoL of hypertensive patients who had comorbid conditions was significant in the case of renal, respiratory, visual problems, and dizziness where females had a lesser utility score than males. The study reports on significant determinants which should be taken into account in an attempt to improve the health-related quality of life of hypertensive patients.
Subject(s)
Hypertension , Quality of Life , Algorithms , Cross-Sectional Studies , Dizziness , Female , Health Status , Humans , Hypertension/epidemiology , Male , Surveys and QuestionnairesABSTRACT
Clotting time of lower gastro intestinal bleeding (LGIB) can be reduced by using simple, cost-effective, and naturally occurring halloysite nanotubes (HNTs). The present study aimed to decrease the clotting time by the application of chitosan (CHT) and its microcomposites (MCs) prepared by suspension emulsification technique with HNTs (CHT/HNTs MC). Physicochemical properties, X-Ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and percentage release of ciprofloxacin from CHT/HNTs MCs was evaluated. In-vitro procoagulant activity of CHT, HNTs and their complexes CHT/HNTs MCs was performed on rabbit blood which was confirmed by a rat tail amputation. Direct relation of HNTs was observed for the whole-blood clotting kinetics i.e., 2% HNTs showed a maximum 66.0% increase in the clotting ability as compared with pure CHT. Interestingly, rat-tail amputation studies showed comparative results of CHT, HNTs, and CHT/HNTs MCs. A total of 75% permeation of ciprofloxacin of CHT/HNTs MCs on rat intestinal membrane was observed within 3 h, confirming their SR behavior. Furthermore, improved hemostatic and clotting properties were CHT/HNTs MC1 > CHT/HNTs MC2 > CHT/HNTs MC3 > CHT > HNTs, respectively. Thus, it provided the control of bleeding disorders in LGIB with any antibacterial agents, particularly ciprofloxacin.
Subject(s)
Chitosan , Hemostatics , Nanotubes , Animals , Chitosan/chemistry , Ciprofloxacin/pharmacology , Clay/chemistry , Delayed-Action Preparations/pharmacology , Nanotubes/chemistry , Rabbits , RatsABSTRACT
PURPOSE: The current study proposed the simple, eco-friendly and cost-effective synthesis of carboxymethyl cellulose (CMC) structured silver-based nanocomposite (CMC-AgNPs) using Syzygium aromaticum buds extract. METHODS: The CMC-AgNPs were characterized by ultraviolet (UV) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transmission infra-red (FTIR), energy-dispersive X-ray (EDX), and dynamic light scattering (DLS) techniques. The synthesized nanocomposites were evaluated for their bactericidal kinetics, in-vivo anti-inflammatory, anti-leishmaniasis, antioxidant and cytotoxic activities using different in-vitro and in-vivo models. RESULTS: The spherical shape nanocomposite of CMC-AgNPs was synthesized with the mean size range of 20-30 nm, and the average pore diameter is 18.2 nm while the mean zeta potential of -31.6 ± 3.64 mV. The highly significant (P < 0.005) antibacterial activity was found against six bacterial strains with the ZIs of 24.6 to 27.9 mm. More drop counts were observed in Gram-negative strains after 10 min exposure with CMC-AgNPs. Significant damage in bacterial cell membrane was also observed in atomic force microscopy (AFM) after treated with CMC-AgNPs. Nanocomposite showed highly significant anti-inflammatory activity in cotton pellet induced granuloma model (Phase I) in rats with the mean inhibitions of 43.13% and 48.68% at the doses of 0.025 and 0.05 mg/kg, respectively, when compared to control. Reduction in rat paw edema (Phase II) was also highly significant (0.025 mg/kg; 42.39%; 0.05 mg/kg, 47.82%). At dose of 0.05 mg/kg, CMC-AgNPs caused highly significant decrease in leukocyte counts (922 ± 83), levels of CRP (8.4 ± 0.73 mg/mL), IL-1 (177.4 ± 21.3 pg/mL), IL-2 (83.7 ± 11.5 pg/mL), IL-6 (83.7 ± 11.5 pg/mL) and TNF-α (18.3 ± 5.3 pg/mL) as compared to control group. CMC-AgNPs produced highly effective anti-leishmaniasis activity with the viable Leishmania major counts decreased up to 36.7% within 24 h, and the IC50 was found to be 28.41 µg/mL. The potent DPPH radical scavenging potential was also observed for CMC-AgNPs with the IC50 value of 112 µg/mL. Furthermore, the cytotoxicity was assessed using HeLa cell lines with the LC50 of 108.2 µg/mL. CONCLUSION: The current findings demonstrate positive attributes of CMC fabricated AgNPs as a promising antibacterial, anti-inflammatory, anti-leishmaniasis, and antioxidant agent with low cytotoxic potential.
Subject(s)
Metal Nanoparticles , Nanocomposites , Animals , Anti-Bacterial Agents/pharmacology , Carboxymethylcellulose Sodium , HeLa Cells , Humans , Microbial Sensitivity Tests , Plant Extracts , Rats , Silver/pharmacology , X-Ray DiffractionABSTRACT
A new simple, accurate, precise and sensitive liquid chromatographic method for the analysis of Ciprofloxacin in human plasma, suitable for quantification of drug was developed and validated using HPLC-UV method. The analyte was chromatographically separated from endogenous plasma components on a C-18 reversed phase column (5µm, 25cm × 0.46cm) and detected at 278nm. The sample pretreatment was carried out with acetonitrile on 200µl of plasma. The Lower limit of quantification (LLOQ) was 0.04 µg/ml with linearity in the range 0.04-4 µg/ml and coefficient of correlation value (R2)>0.995. The method was successfully validated as per current FDA guidance for necessary parameters and applied to a pilot bioavailability study conducted on six healthy volunteers with marketed Ciprofloxacin 250mg immediate release tablets. The plasma concentrations were subjected to non-compartmental analysis for calculation of pharmacokinetic parameters like Cmax, Tmax, AUCo-t, AUC 0-∞ and t½ etc. The mean values of Cmax and Tmax were found to be 1.35±0.09µg/ml and 1.25±0.27h respectively while for other pharmacokinetic parameters including AUCo-t, AUC0-∞ were found to be 5.98±0.96 µg/ml×h and 6.34±1.07µg/ml×h. The drug exhibited half-life (t½) of 3.94±0.33h. The obtained results proved the suitability of the method for routine pharmacokinetic studies of Ciprofloxacin.
Subject(s)
Anti-Bacterial Agents/blood , Chromatography, Liquid/methods , Ciprofloxacin/blood , Adult , Anti-Bacterial Agents/pharmacokinetics , Biological Availability , Ciprofloxacin/pharmacokinetics , Humans , Limit of Detection , Male , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
The objective was to develop eperisone HCl sustained-release pellets through extrusion spheronization technique and to determine the influence of different hydrophobic (polymeric based and wax-based) and hydrophilic (polymeric based) matrix former on the release of eperisone HCl (BCS class I drug) and on pellet sphericity. The pellet formulations consisted of different hydrophobic and hydrophilic matrix formers like HPMC K4M (10-20%) HPMC K15M (10%), EC (7cps) (10-20%), Carnauba wax (10-20%), Compritol ATO 888 (10-20%), Glyceryl monostearate (10%), lactose and microcrystalline cellulose. The initial burst release of the drug from matrix pellet formulations was effectively controlled by coating with 5% EC (ethylcellulose) dispersion. The dissolution profile and drug release kinetics of coated pellet formulations were determined at both acidic and basic pH medium. SEM (Scanning electron microscope) technique was used to determine the surface morphology and cross-section of F5 and F7 pellet formulation. The mechanism of drug release of coated formulation followed non-Fickian diffusion. FTIR spectroscopy was conducted and no drug and excipients interaction was observed. The results had shown that optimized coated formulation was F5 and F7 which effectively extend the drug release for 12 hours.
Subject(s)
Delayed-Action Preparations/pharmacokinetics , Muscle Relaxants, Central/pharmacokinetics , Propiophenones/pharmacokinetics , Cellulose/analogs & derivatives , Chemistry, Pharmaceutical , Delayed-Action Preparations/chemistry , Drug Development , Drug Liberation , Excipients/chemistry , Fatty Acids , Glycerides , Lactose/analogs & derivatives , Methylcellulose/analogs & derivatives , Microscopy, Electron, Scanning , Muscle Relaxants, Central/administration & dosage , Muscle Relaxants, Central/chemistry , Polymers , Propiophenones/administration & dosage , Propiophenones/chemistry , Spectroscopy, Fourier Transform Infrared , WaxesABSTRACT
PURPOSE: This study systematically investigated the potential of four model drugs (verapamil HCl, flurbiprofen, atenolol, and furosemide), each belonging to a different class of Biopharmaceutics Classification Systems (BCS) to be developed into oral modified release dosage forms after loading with halloysite nanotubes (HNTs). METHODS: The drugs were studied for their loading (mass gain %) by varying solvent system, method, pH, and ratios of loading into the nanotubes using D-optimal split-plot design with the help of Design Expert software. Drug-loaded halloysites were characterized by XRD, DTA, FTIR, SEM, and HPLC-UV-based assay procedures. Dissolution studies were also performed in dissolution media with pH 1.2, 4.5, and 6.8. Moreover, the optimized samples were evaluated under stress stability conditions for determining prospects for the development of oral dosage forms. RESULTS: As confirmed with the results of XRD and DTA, the drugs were found to be converted into amorphous form after loading with halloysite (HNTs). The drugs were loaded in the range of ~7-9% for the four drugs, with agitation providing satisfactory and equivalent loading as compared to vacuum plus agitation based reported methods. FTIR results revealed either only weak electrostatic (verapamil HCl and flurbiprofen) or no interaction with the surface structure of the HNTs. The dissolution profiling depicted significantly retarded release of drugs with Fickian diffusion from a polydisperse system as a model that suits well for the development of oral dosage forms. HPLC-UV-based assay indicated that except furosemide (BCS class IV), the other three drugs are quite suitable for development for oral dosage forms. CONCLUSION: The four drugs investigated undergo phase transformation with HNTs. While agitation is an optimum method for loading drugs with various physicochemical attributes into HNTs; solvent system, loading ratios and pH play an important role in the loading efficiency respective to the drug properties. The study supports the capability of developing HNT-based modified release oral dosage forms for drugs with high solubility.
Subject(s)
Biopharmaceutics/classification , Clay/chemistry , Drug Delivery Systems , Drug Liberation , Nanotubes/chemistry , Pharmaceutical Preparations/administration & dosage , Administration, Oral , Aluminum Silicates/chemistry , Kinetics , Spectroscopy, Fourier Transform Infrared , X-Ray DiffractionABSTRACT
The 2019 novel coronavirus (2019-nCoV), commonly known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), was first revealed in late 2019 in Wuhan city, Hubei province, China. It was subsequently spread globally and thereby declared as a pandemic by WHO in March 2020. The disease causes severe acute respiratory illness and is highly contagious due to the fast-onward transmission. As of the mid of November 2020, the disease has affected 220 countries with more than 16 million active cases and 1.3 million deaths worldwide. Males, pregnant women, the elderly, immunosuppressed patients, and those with underlying medical conditions are more vulnerable to the disease than the general healthy population. Unfortunately, no definite treatment is available. Although remdesivir as an antiviral had been approved for use in those above 12 years of age and 40 kg weight group, it has been observed to be ineffective in large-scale SOLIDARITY trials by WHO. Moreover, dexamethasone has been found to increase the recovery rate of ventilated patients; oxygen and inhaled nitric oxide as a vasodilator have been given emergency expanded access. In addition, more than 57 clinical trials are being conducted for the development of the vaccines on various platforms. Two vaccines were found to be significantly promising in phase III results. It is concluded that till the approval of a specific treatment or development of a vaccine against this deadly disease, the preventive measures should be followed strictly to reduce the spread of the disease.
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PURPOSE: To develop the osmotically controlled-release gastroprokinetic metoclopramide HCl tablets, using quality by design (QbD)-numerical and graphical optimization technique for the treatment of gastroparesis and prophylaxis of delayed nausea and vomiting induced by low-high emetogenic chemotherapy. METHODS: Formulations were designed by central composite design using Design Expert version 11.0.0, with osmogen concentration (X1), orifice size (X2), and tablet weight gain after coating (X3) as input and in-vitro drug release at 1hr. (Y1), 6 hrs. (Y2), and 12 hrs. (Y3), and the regression coefficient of drug release data fitted to zero-order, RSQ zero (Y4) as output variables. Core tablets prepared by direct compression were coated with Opadry® CA. The experimental design was validated by the polynomial equation. A correlation between predicted and observed values was evaluated by random checkpoint analysis. The optimized formulations were characterized for drug release, pH effect, osmolarity, agitation intensity, surface morphology, and stability study, and were subjected to accelerated studies according to ICH guidelines. RESULTS: The interaction charts and response surface plots deduced a significant simultaneous effect of X variables on in vitro drug release and RSQ zero. The numerical optimization model predicted >90% drug release with X1 (13.30%), X2 (0.6 mm), and X3 (7.96%). Random checkpoint analysis showed a good correlation between predicted and observed values. The optimized formulation followed zero-order kinetics (r2=0.9703) drug release. Shelf life calculated was 2.8 years as per ICH guidelines. CONCLUSION: The QbD-based approach was found successful in developing controlled release osmotic tablets of metoclopramide HCl, for reducing the dosage frequency, better emetic control, and improve patient compliance.
Subject(s)
Drug Development , Infusion Pumps, Implantable , Metoclopramide/chemistry , Drug Liberation , Humans , Kinetics , Metoclopramide/chemical synthesis , TabletsABSTRACT
PURPOSE: The present study reports chitosan functionalized green synthesized CS-AgNPs, conjugated with amoxicillin (AMX), cefixime (CEF), and levofloxacin (LVX) for safe and enhanced antibacterial activity. METHODS: The CS-AgNPs and conjugates CS-AgNPs+AMX CS-AgNPs+CEF, and CS-AgNPs+LVX were characterized by UV-Vis, FTIR, SEM, TEM, EDX spectroscopy. The size distribution and zeta potential were measured using the dynamic light scattering (DLS) technique. The interaction between CS-AgNPs and antibiotic molecules was also investigated using UV-Vis spectroscopy at the concentrations of 5, 50, 500, and 5000 µM for each antibiotic. Antibacterial activity and synergism were assessed by the Fractional Inhibitory Concentration (FIC) index. The mechanism for synergistic activity was investigated by the detection of hydroxyl species based on the chemiluminescence of luminol. The biocompatibility index (BI) was calculated from IC50 using the HeLa cell line. In vivo toxicity and tissue distribution of silver ions were evaluated on Sprague Dawley rats. Physical interactions of antibiotics and significant (P<0.05) antibacterial activity were observed after loading on CS-AgNPs surfaces. RESULTS: The spherical shape nanocomposites of CS-AgNPs with different antibiotics were prepared with mean size ranges of 80-120 nm. IC50 of antibiotics-conjugated CS-AgNPs decreased compared to CS-AgNPs. The biocompatibility (BI) index showed that antibiotics-conjugated CS-AgNPs have high antibacterial potential and low toxicity. Highly significant (P<0.005) increase in the generation of hydroxyl species indicated the radical scavenging mechanism for synergistic activity of CS-AgNPs after combined with different antibiotics. Biochemical analysis and histopathological examinations confirmed low toxicity with minor hepatotoxicity at higher doses. After oral administration, extensive distribution of Ag ion was observed in spleen and liver. CONCLUSION: The study demonstrates positive attributes of antibiotics-conjugated CS-AgNPs, as a promising antibacterial agent with low toxicity.