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As a common pyrethroid insecticide, allethrin is widely used for various purposes in agriculture and home applications. At present, allethrin residues have been frequently detected worldwide, yet little is known about the kinetics and degradation mechanisms of this insecticide. In this study, a highly efficient allethrin-degrading bacterium, Bacillus megaterium strain HLJ7, was obtained through enrichment culture technology. Strain HLJ7 can remove 96.5% of 50 mg L-1 allethrin in minimal medium within 11 days. The first-order kinetic analysis of degradation demonstrated that the half-life of allethrin degradation by strain HLJ7 was 3.56 days, which was significantly shorter than the 55.89 days of the control. The Box-Behnken design of the response surface method optimized the degradation conditions for strain HLJ7: temperature 32.18 °C, pH value 7.52, and inoculation amount 1.31 × 107 CFU mL-1. Using Andrews equation, the optimal concentration of strain HLJ7 to metabolize allethrin was determined to be 21.15 mg L-1, and the maximum specific degradation rate (qmax), half-rate constant (Ks) and inhibition coefficient (Ki) were calculated to be 1.80 d-1, 1.85 mg L-1 and 68.13 mg L-1, respectively. Gas chromatography-mass spectrometry identified five intermediate metabolites, suggesting that allethrin could be degraded firstly by cleavage of its carboxylester bond, followed by degradation of the five-carbon ring and subsequent metabolism. The results of soil remediation experiments showed that strain HLJ7 has excellent bioremediation potential in the soils. After 15 days of treatment, about 70.8% of the initial allethrin (50 mg kg-1) was removed and converted into nontoxic intermediate metabolites, and its half-life was significantly reduced in the soils. Taken together, these findings shed light on the degradation mechanisms of allethrin and also highlight the promising potentials of B. megaterium HLJ7 in bioremediation of allethrin-comtaminated environment.
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Bacillus megaterium , Inseticidas , Poluentes do Solo , Aletrinas , Bacillus megaterium/metabolismo , Biodegradação Ambiental , Inseticidas/metabolismo , Cinética , Solo/química , Microbiologia do Solo , Poluentes do Solo/metabolismo , ÁguaRESUMO
PURPOSE: three dimensional (3-D) virtual planning is an example of computer assisted surgery that improved management of composite tissue defects. However, converting the 3-D construct into two dimensional format is challenging. The purpose of this study was to assess 3-D virtual planning of complex heel defects for better optimized reconstruction. PATIENTS AND METHODS: a prospective analysis of 10 patients [9 male and 1 female; mean age = 27.9 years] with post-traumatic heel defects was performed. Heel defects comprised types II (three patients) or III (seven patients) according to Hidalgo and Shaw and were managed using anterolateral thigh (ALT) free flap adopting 3-D virtual planning of the actual defect which was converted into a silicone two dimensional mold. The mean definitive size of the defects was 63.4 cm3 . Functional, aesthetic, and sensory evaluations of both donor and recipient sites were performed 1 year after surgery. RESULTS: Six patients received thinned ALT (mean size = 139 cm3 ) while four patients received musculofasciocutaneous ALT flap (mean size = 199 cm3 ). One flap exhibited partial skin flap necrosis. Another flap was salvaged after re-exploration secondary to venous congestion. The mean follow-up was 20.2 months. The Maryland foot score showed 4 excellent, 5 good, and 1 fair cases. The mean American Orthopedic Foot and Ankle hind foot scoring was 76.3 (range: 69-86). All patients regained their walking capability. CONCLUSIONS: 3-D virtual planning of complex heel defects facilitates covering non-elliptical defects while harvesting a conventional elliptical flap with providing satisfactory functional outcomes and near-normal contour, volume, and sensibility.
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Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Adulto , Feminino , Retalhos de Tecido Biológico/cirurgia , Calcanhar/cirurgia , Humanos , Masculino , Procedimentos de Cirurgia Plástica/métodos , Lesões dos Tecidos Moles/cirurgia , Coxa da Perna/cirurgiaRESUMO
PURPOSE: Polysorbate excipients are commonly used as surfactants to stabilize therapeutic proteins in formulations. Degradation of polysorbates could lead to particle formation and instability of the drug formulation. We investigated how the fatty acid composition of polysorbate 80 impacts the degradation profile, particle formation, and product stability under stress conditions. METHODS: Two polysorbate 80-containing therapeutic protein formulations were reformulated with either Polysorbate 80 NF synthesized from a fatty acid mixture that contains mainly oleic acid (≥58%) or a version of polysorbate 80 synthesized with high oleic acid (>98%). Stress conditions, including high temperature and esterase spiking, were applied and changes to both the polysorbate and the therapeutic protein product were investigated for stability, purity, innate immune response and biological activity. RESULTS: The addition of esterase and storage at 37°C led to significant hydrolysis of the polysorbate and increases in sub-visible particle formation for both polysorbates tested. The fatty acid composition of polysorbate 80 did not directly alter the stability profile of either therapeutic protein as measured by size exclusion chromatography, or significantly impact innate immune response or biological activity. However, formulations with Polysorbate 80 NF showed greater propensity for sub-visible particle formation under stress conditions. CONCLUSIONS: These results suggest that composition of fatty acids in polysorbate 80 may be a promoter for sub-visible particulate formation under the stress conditions tested but may not impact protein aggregation or biological activity.
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Excipientes/química , Ácidos Graxos/química , Polissorbatos/química , Rituximab/química , Linhagem Celular Tumoral , Química Farmacêutica , Composição de Medicamentos/métodos , Humanos , Imunidade Inata/efeitos dos fármacos , Leucócitos Mononucleares , Estabilidade Proteica , Rituximab/farmacologia , Rituximab/uso terapêuticoRESUMO
Macrolides are bacteriostatic antibiotics with a broad spectrum of activity against Gram-positive bacteria. The aim of this study was to systematically review and meta-analyze the association between infantile hypertrophic pyloric stenosis (IHPS) and macrolides. Nine databases were searched systematically for studies with information on the association between macrolides and IHPS. We combined findings using random effects models. Our study revealed 18 articles investigating the association between macrolides and IHPS. There was a significant association between the development of IHPS and erythromycin (2.38, 1.06-5.39). The association was strong when erythromycin was used during the first 2 weeks of life (8.14, 4.29-15.45). During breastfeeding, use of macrolides showed no significant association with IHPS in infants (0.96, 0.61-1.53). IHPS was not associated with erythromycin (1.11, 0.9-1.36) or macrolides use during pregnancy (1.15, 0.98-1.36).Conclusions: There is an association between erythromycin use during infancy and developing IHPS in infants. However, no significant association was found between macrolides use during pregnancy or breastfeeding. Additional large studies are needed to further evaluate potential association with macrolide use. What is known? ⢠Erythromycin intake in the first 2 weeks of life is associated with an increased risk of pyloric stenosis. What is New? ⢠There is currently no evidence of significant association between macrolides use during pregnancy or breastfeeding and pyloric stenosis.
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Antibacterianos/efeitos adversos , Macrolídeos/efeitos adversos , Estenose Pilórica Hipertrófica/induzido quimicamente , Aleitamento Materno , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Fatores de RiscoRESUMO
Amorphous and crystalline solids are commonly found together in a variety of pharmaceutical and food products. In this study, the influence of co-formulation of amorphous maltodextrins (MDs) and crystalline sucrose (S) on moisture sorption, deliquescence, and glass transition (Tg) properties of powder blends was investigated. Individual components and binary mixtures of four different molecular weight MDs with sucrose in 1:1 w/w ratios were exposed to various relative humidity (RH) environments and their equilibrium and dynamic moisture contents were monitored. The deliquescence point (RH0) and dissolution behavior of sucrose alone and in blends was also monitored by polarized light microscopy and second harmonic generation imaging. In S:MD blends, the deliquescence RH of sucrose was lower than the RH0 of sucrose alone, and synergistic moisture sorption also occurred at RHs lower than the RH0. Intimate contact of sucrose crystals with the amorphous MDs resulted in complete dissolution of sucrose at RH < RH0. When blends were stored at conditions exceeding the Tg of the individual MDs (25 °C and 60%, 49% and 34%RH for MD21, MD29 and MD40, respectively), the Tg of the blends was lower than that of individual MDs. Thus, co-formulation of amorphous MDs with crystalline sucrose sensitizes the blend to moisture, potentially leading to deleterious changes in the formulation if storage conditions are not adequately controlled.
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Polissacarídeos/química , Sacarose/química , Água/química , Cristalização , Umidade , Temperatura de TransiçãoRESUMO
The COVID-19 pandemic is the largest global public health outbreak in the 21st century so far. It has contributed to a significant increase in the generation of waste, particularly personal protective equipment and hazardous medical, as it can contribute to environmental pollution and expose individuals to various hazards. To minimize the risk of infection, the entire surrounding environment should be disinfected or neutralized regularly. Effective medical waste management can add value by reducing the spread of COVID-19 and increasing the recyclability of materials instead of sending them to landfill. Developing an antiviral coating for the surface of objects frequently used by the public could be a practical solution to prevent the spread of virus particles and the inactivation of virus transmission. Relying on an abundance of engineered materials identifiable by their useful physicochemical properties through versatile chemical functionalization, nanotechnology offers a number of approaches to address this emergency. Here, through a multidisciplinary perspective encompassing various fields such as virology, biology, medicine, engineering, chemistry, materials science, and computer science, we describe how nanotechnology-based strategies can support the fight against COVID-19 well as infectious diseases in general, including future pandemics. In this review, the design of the antiviral coating to combat the spread of COVID-19 was discussed, and technological attempts to minimize the coronavirus outbreak were highlighted.
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COVID-19 vaccines are crucial to control the pandemic and avoid COVID-19 severe infections. The rapid evolution of COVID-19 variants such as B.1.1.529 is alarming, especially with the gradual decrease in serum antibody levels in vaccinated individuals. Middle Eastern countries were less likely to accept the initial doses of vaccines. This study was directed to determine COVID-19 vaccine booster acceptance and its associated factors in the general population in the MENA region to attain public herd immunity. We conducted an online survey in five countries (Egypt, Iraq, Palestine, Saudi Arabia, and Sudan) in November and December 2021. The questionnaire included self-reported information about the vaccine type, side effects, fear level, and several demographic factors. Kruskal−Wallis ANOVA was used to associate the fear level with the type of COVID-19 vaccine. Logistic regression was performed to confirm the results and reported as odds ratios (ORs) and 95% confidence intervals. The final analysis included 3041 fully vaccinated participants. Overall, 60.2% of the respondents reported willingness to receive the COVID-19 booster dose, while 20.4% were hesitant. Safety uncertainties and opinions that the booster dose is not necessary were the primary reasons for refusing the booster dose. The willingness to receive the booster dose was in a triangular relationship with the side effects of first and second doses and the fear (p < 0.0001). Females, individuals with normal body mass index, history of COVID-19 infection, and influenza-unvaccinated individuals were significantly associated with declining the booster dose. Higher fear levels were observed in females, rural citizens, and chronic and immunosuppressed patients. Our results suggest that vaccine hesitancy and fear in several highlighted groups continue to be challenges for healthcare providers, necessitating public health intervention, prioritizing the need for targeted awareness campaigns, and facilitating the spread of evidence-based scientific communication.
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The objective of the present study was to formulate and evaluate microemulsion systems for topical delivery of clotrimazole (CTM). The solubility of CTM in various oils was determined to select the oil phase of the microemulsion systems. Pseudoternary phase diagrams were constructed to identify the area of microemulsion existence. Five CTM microemulsion formulations (M1-M5) were prepared and evaluated for their thermodynamic stability, pH, refractive index, droplet size, viscosity, and in vitro release across cellulose membrane. Among the prepared microemulsion formulations, M3 (lemon oil/Tween 80/n-butanol/water) and M4 (isopropyl myristate/Tween 80/n-butanol/water) microemulsion systems were found to be promising according to their physical properties and CTM cumulative percentage release. Gel form of M3 and M4 were prepared using 1% Carbopol 940 as the hydrogel matrix. Both formulations were evaluated in the liquid and gel forms for drug retention in the skin in comparison to the marketed CTM topical cream and their stability examined after storage at 40°C for 6 months. Microemulsion formulations achieved significantly higher skin retention for CTM over the CTM cream. Stability studies showed that M4 preparations were more stable than M3. The in vitro anti-fungal activity of M4 against Candida albicans was higher than that of the conventional cream. Moreover, clinical evaluation proved the efficacy and tolerability of this preparation in the treatment of various topical fungal infections.
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Administração Tópica , Antifúngicos , Clotrimazol , Dermatomicoses/tratamento farmacológico , Emulsões/química , Adolescente , Adulto , Animais , Antifúngicos/administração & dosagem , Antifúngicos/química , Álcool Benzílico/química , Clotrimazol/administração & dosagem , Clotrimazol/química , Clotrimazol/uso terapêutico , Composição de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Estabilidade de Medicamentos , Emulsões/administração & dosagem , Feminino , Glicerol/análogos & derivados , Glicerol/química , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Miristatos/química , Óleos/química , Ácido Oleico/química , Tamanho da Partícula , Óleos de Plantas/química , Polissorbatos/química , Absorção Cutânea , Solubilidade , Tensoativos/químicaRESUMO
Objective: To validate an Arabic version of the Danish Prostatic Symptom Score (DAN-PSS), a self-administered quality-of-life questionnaire. Patients and methods: The reliability of the Arabic DAN-PSS was assessed by determining the internal consistency (Cronbach's α coefficient) and by assessing the test-retest reliability (Kappa [κ] test). Inter-domain associations were examined using Spearman's correlation coefficient (r). The discrimination validity was evaluated using receiver operating characteristic (ROC) curves. The sensitivity to change of the questionnaire and its individual items was assessed before and after intervention using a paired t-test. Results: In all, 106 men (55 patients with BPH and 51 without BPH symptoms) were included. A high level of internal consistency amongst the three domains of the answered Arabic DAN-PSS questionnaire was observed (Cronbach's α > 0.70). Also, there was a good correlation between storage and voiding (r = 0.75; P < 0.001) and post-micturition symptoms domains (r = 0.51; P < 0.001). Voiding and post-micturition symptoms domains also had a good correlation (r = 0.51; P < 0.001). The agreement between the test and retest scores had a κ value of 0.83 (P < 0.001). The ROC curve had an area under the curve of 0.98. The sensitivity to change comparing patients with BPH who received medical or surgical intervention revealed Arabic DAN-PSS mean (SD) scores of 34.7 (17.7) and 17 (8.7) before and after the intervention, respectively (P < 0.001). Conclusion: The Arabic DAN-PSS is a clear questionnaire, valid, reliable, and responsive that can be used for BPH associated with lower urinary tract symptoms assessment and follow-up in clinical practice and research in Arabic-speaking patients. Abbreviations: AUC: area under the curve; BPH: benign prostatic hyperplasia; CI: confidence interval; DAN-PSS: Danish Prostatic Symptom Score; DRE: digital rectal examination; ICIQ-MLUTS: International Consultation on Incontinence Male LUTS Questionnaire; ICS: international continence society; IPSS: international Prostatic Symptom Score; IPSS-Arb: Arabic version of the IPSS; LUTS: lower urinary tract symptoms; PSA: prostatic specific antigen; PSS: prostatic symptom score; QoL: quality of life; ROC: receiver operating characteristic; UTI: urinary tract infection.
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The use of various veterinary antibiotics (VAs) in animal husbandry raises serious concerns about the development of antibiotic resistance. Antibiotics such as tetracycline, oxytetracycline, sulfadiazine, norfloxacin, and enrofloxacin are the most frequently used antimicrobial compounds in animal husbandry and generate large eco-toxicological effects; however, they are still difficult to determine in a complex matrix such as swine manure. This study has developed an effective method for detecting five VAs in swine manure using Ultra-High-Performance Liquid Chromatography-Diode Array Detector (UHPLC-DAD) coupled with on-line solid-phase extraction (SPE). The results show that the mobile phase of ACN/0.01 M oxalic acid was the optimum at pH 3.0. VAs in a swine manure matrix were extracted using solid extraction buffer solution (T3) with 97.36% recovery. Sensitivity, accuracy, and precision were also evaluated. The validity study showed good linearity (R2 > 0.99). Limit of detection (LOD) was found to be from 0.1 to 0.42 µg mL-1 in the liquid fraction and from 0.032 to 0.58 µg g-1 dw in the solid fraction. The corresponding values of the limit of quantification (LOQ) ranged from 0.32 to 1.27 µg mL-1 for the liquid fraction and from 0.096 to 1.77 µg g-1 dw for the solid fraction. Therefore, the proposed method showed the potential applicability for detecting different antibiotic compounds from swine manure samples.
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Considering the advantageous for the rectal administration of non-steroidal anti-inflammatory drugs, the objective of this study was to formulate and evaluate rectal mucoadhesive hydrogels loaded with diclofenac-sodium chitosan (DFS-CS) microspheres. Hydroxypropyl methylcellulose (HPMC; 5%, 6%, and 7% w/w) and Carbopol 934 (1% w/w) hydrogels containing DFS-CS microspheres equivalent to 1% w/w active drug were prepared. The physicochemical characterization revealed that all hydrogels had a suitable pH for rectal application (6.5-7.4). The consistency of HPMC hydrogels showed direct proportionality to the concentration of the gelling agent, while carbopol 934 gel showed its difficulty for rectal administration. Farrow's constant for all hydrogels were greater than one indicating pseudoplastic flow. In vitro drug release from the mucoadhesive hydrogel formulations showed a controlled drug release pattern, reaching 34.6-39.7% after 6 h. The kinetic analysis of the release data revealed that zero-order was the prominent release mechanism. The mucoadhesion time of 7% w/w HPMC hydrogel was 330 min, allowing the loaded microspheres to be attached to the surface of rectal mucosa. Histopathological examination demonstrated the lowest irritant response to the hydrogel loaded with DFS-CS microspheres in response to other forms of the drug.
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Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Diclofenaco/administração & dosagem , Diclofenaco/química , Sistemas de Liberação de Medicamentos , Hidrogéis/química , Adesivos , Administração Retal , Quitosana/química , Composição de Medicamentos , Concentração de Íons de Hidrogênio , Microesferas , ReologiaRESUMO
OBJECTIVES:: To assess the influence of selective serotonin reuptake inhibitor (SSRI) use on jawbone and bone mineral density by retrospective analysis of panoramic radiographs. METHODS:: Radiographic and clinical records were sourced from the Division of Orthodontics and TMJD, Eastman Institute for Oral Health, University of Rochester. Randomly selected adults (20-65 years) were categorized into: "Active" (with history of SSRI use of >6 months) and a "Control" group. Panoramic indices: Klemetti index (KI), panoramic mandibular index, antegonial notching index, condylar pathology, mandibular cortical width (MCW)â and mean ramus height were recorded. Frequency-weighted Χ2 tests and multinomial regression controlling for age and gender were applied to categorical indices (KI, condylar pathology, antegonial notching index). Multivariate generalized linear modeling was applied to mean ramus height, MCW and panoramic mandibular index. Multiple regression analyses determined: (a) panoramic indices that best predicted SSRI use, and (b) independent predictors of KI category. RESULTS:: 64 SSRI users and 48 Controls were assessed. SSRI users had significantly higher odds of having worse KI status than normal [mildly to moderately eroded cortex: odds ratio (OR) = 2.926, 95% CI (1.07-8.04) and severely eroded cortex: OR = 19.86, 95% CI (3.91-100.69)], more frequent flat condylar anatomy (right side: p = 0.009, left side: p < 0.001) but greater ramus height (p = 0.001) and mandibular cortical width (p = 0.032). Age, gender, SSRI use each significantly impacted KI. Only SSRI use significantly impacted condylar pathology, ramus height and MCW. KI category (OR = 1.3) was the best panoramic predictor of SSRI use. Conversely, KI category C3 was significantly predicted by SSRI use (OR = 31.2, p = 0.002), female gender (17.5, p = 0.006), and severe antegonial notching (OR = 1289, p < 0.001). CONCLUSIONS:: SRRI use was significantly associated with worse panoramic morphometric indices: KI, condylar pathology, ramus height, and MCW, where KI was its strongest predictor. Worse KI was independently predicted by SSRI use.
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Densidade Óssea , Radiografia Panorâmica , Inibidores Seletivos de Recaptação de Serotonina , Adulto , Idoso , Densidade Óssea/efeitos dos fármacos , Feminino , Humanos , Masculino , Mandíbula , Pessoa de Meia-Idade , Estudos Retrospectivos , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversosRESUMO
As diagnostic and therapeutic modalities for Hodgkin's Lymphoma (HL) continue to improve, patient-related factors affecting survival become more difficult to identify. Very little is known about the relationship between the primary site of lymph node (LN) involvement and survival of HL patients. We retrospectively analyzed the United States Surveillance, Epidemiology and End Results (SEER) database for 12,658 HL patients reported between 1973 and 2010 using survival analysis and time-interval multiple logistic regression (MLR) to disclose that relationship. The effect of all primary LN sites on the survival of HL patients was supported. The intra-abdominal (IAB) primary LN site was significantly associated with the worst survival. The pelvic (P) LN sites were significantly and independently associated with nearly 2 times and 2.5 times the probability of having 1-year overall mortality (OM) and 1-year cancer-specific mortality (CSM), respectively. Head, face and neck (HFN) primary LN sites were significant and independent predictors of better overall and HL-specific survival. A worse survival with the intra-abdominal primary LN site was probably related to their association with higher age, or advanced stages of HL. The biological basis behind the aggressiveness of intra-abdominal and pelvic LN sites is yet to be investigated.
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Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Linfonodos/patologia , Feminino , História do Século XX , História do Século XXI , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/história , Humanos , Estimativa de Kaplan-Meier , Masculino , Razão de Chances , Vigilância da População , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Programa de SEER , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
The aims of the study were to evaluate the effect of high shear mixer (HSM) granulation process parameters and scale-up on wet mass consistency and granulation characteristics. A mixer torque rheometer (MTR) was employed to evaluate the granulating solvents used (water, isopropanol, and 1:1 vol/vol mixture of both) based on the wet mass consistency. Gral 25 and mini-HSM were used for the granulation. The MTR study showed that the water significantly enhanced the beta-cyclodextrin (beta CD) binding tendency and the strength of liquid bridges formed between the particles, whereas the isopropanol/water mixture yielded more suitable agglomerates. Mini-HSM granulation with the isopropanol/water mixture (1:1 vol/vol) showed a reduction in the extent of torque value rise by increasing the impeller speed as a result of more breakdown of agglomerates than coalescence. In contrast, increasing the impeller speed of the Gral 25 resulted in higher torque readings, larger granule size, and consequently, slower dissolution. This was due to a remarkable rise in temperature during Gral granulation that reduced the isopropanol/water ratio in the granulating solvent as a result of evaporation and consequently increased the beta CD binding strength. In general, the HSM granulation retarded ibuprofen dissolution compared with the physical mixture because of densification and agglomeration. However, a successful HSM granulation scale-up was not achieved due to the difference in the solvent mixture's effect from 1 scale to the other.
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Anti-Inflamatórios não Esteroides/química , Excipientes/química , Ibuprofeno/química , Tecnologia Farmacêutica/métodos , beta-Ciclodextrinas/química , 2-Propanol/química , Química Farmacêutica , Força Compressiva , Composição de Medicamentos , Pós , Reologia , Solubilidade , Solventes/química , Estresse Mecânico , Temperatura , Fatores de Tempo , Torque , Volatilização , Água/químicaRESUMO
The aim of this study was to examine the relationship between physical characteristics of compacted ribbons and their thermal effusivity in an attempt to evaluate the feasibility of using effusivity for in-process monitoring of roller compaction. In this study, thermal effusivity, solid fraction, tensile strength, and Young's modulus of ribbons of microcrystalline cellulose (MCC), anhydrous lactose, and placebo (PBO) formulations containing various ratios of MCC to anhydrous lactose (75:20, 55:40, 40:55, and 20:75) were determined at various compaction pressures (25-150 bars). The effusivity-square root of solid fraction relationship was linear for MCC and all the PBO formulations but was a second-order polynomial function for lactose. This could be due to the predominant deformation of lactose by brittle fracture, which might have significantly increased the number and size of contact points between particles, causing a change in thermal conductivity along with a density change. The effusivity-tensile strength and effusivity-Young's modulus relationships were best described by logarithmic functions for MCC but were linear for lactose up to a compaction pressure of 65 bars. There were similar relationships for effusivity with tensile strength and Young's modulus for all PBO formulations except PBO IV, which might have been due to the deformation of lactose, the largest component in this formulation. Strong correlations between effusivity and physical properties of ribbons were established. Although these correlations were formulation-dependent, they demonstrate the possibility of using effusivity as a tool in monitoring roller compaction.
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Celulose/química , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Excipientes/química , Teste de Materiais/métodos , Tecnologia Farmacêutica/métodos , Termografia/métodos , Algoritmos , Difusão , Avaliação Pré-Clínica de Medicamentos/métodos , PressãoRESUMO
The effects of coformulating amorphous maltodextrins (MDs) and crystalline fructose, a deliquescent solid, on the moisture sorption, deliquescence point (RH0 ), and glass transition temperature (Tg ) behaviors were determined. Moisture sorption profiles of binary fructose:MD mixtures and individual ingredients were generated using controlled relative humidity (RH) desiccators and by dynamic vapor sorption techniques. Blends exhibited synergistic moisture uptake at RHs below the RH0 of fructose, attributed to partial dissolution of fructose in plasticized MD matrices without a significant reduction in the RH0 of the undissolved fructose. Increasing storage temperature decreased the onset RH for moisture sorption synergy. At all storage RHs, the measured Tg (2nd scan) was significantly reduced in fructose:MD mixtures compared to individual MDs, and was related to both the synergistic moisture uptake in the blends and heat-induced ternary fructose-MD-water interactions in the differential scanning calorimeter. Differences were found between the behavior of fructose:MD blends and previous reports of sucrose:MD and NaCl:MD blends, caused in part by the lower RH0 of fructose. The enhanced moisture sorption in blends of deliquescent and amorphous ingredients could lead to problematic moisture-induced changes if storage conditions are not controlled.
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Análise de Alimentos , Frutose/química , Polissacarídeos/química , Água/química , Cristalização , Cloreto de Sódio , Sacarose/química , TemperaturaRESUMO
The objective of this study was to prepare cubosomal nanoparticles containing a hydrophilic anticancer drug 5-fluorouracil (5-FU) for liver targeting. Cubosomal dispersions were prepared by disrupting a cubic gel phase of monoolein and water in the presence of Poloxamer 407 as a stabilizer. Cubosomes loaded with 5-FU were characterized in vitro and in vivo. In vitro, 5-FU-loaded cubosomes entrapped 31.21% drug and revealed nanometer-sized particles with a narrow particle size distribution. In vitro 5-FU release from cubosomes exhibited a phase of rapid release of about half of the entrapped drug during the first hour, followed by a relatively slower drug release as compared to 5-FU solution. In vivo biodistribution experiments indicated that the cubosomal formulation significantly (P<0.05) increased 5-FU liver concentration, a value approximately 5-fold greater than that observed with a 5-FU solution. However, serum serological results and histopathological findings revealed greater hepatocellular damage in rats treated with cubosomal formulation. These results demonstrate the successful development of cubosomal nanoparticles containing 5-FU for liver targeting. However, further studies are required to evaluate hepatotoxicity and in vivo antitumor activity of lower doses of 5-FU cubosomal formulation in treatment of liver cancer.
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The objectives of this study were to evaluate the bioavailability of cogranulated and oven-dried ibuprofen (IBU) and beta-cyclodextrin (betaCD), in comparison to a physical mixture, and to examine the effect of endogenous bile on the bioavailability of the drug. In vitro dissolution studies were performed using USP type 2 apparatus. The granules and physical mixture were administered perorally in a crossover fashion, to male Wistar bile duct-nonligated rats. The granules were also perorally administered to bile duct-ligated rats. Blood samples were taken at different time intervals and the plasma analyzed for IBU. Dissolution of granules was faster than the physical mixture due to faster IBU-betaCD complex formation in solution from the former than the latter. The in vivo study showed that C(max), AUC(0-8), and the absolute bioavailability for the granules (49.0 microg/mL, 57.0 h x microg/mL and 80.6%, respectively) were almost one and half times that of the physical mixture (32.2 microg/mL, 38.4 h x microg/mL and 53.1%, respectively). However, in bile duct-ligated rats, lower C(max) and AUC(0-8) (15.9 microg/mL and 14.4 h x microg/mL, respectively) were obtained for the granules. Phase solubility study of IBU in an aqueous betaCD solution in the presence of the bile salt (sodium cholate), showed an increase in the solubility of IBU. Moreover, the stability constant value for the IBU-betaCD complex was also found to decrease as the sodium cholate concentration increased. These results indicated that the enhancement in the bioavailability of IBU was due to faster in-solution complex formation, and micelllar solubilization by the bile salt.
Assuntos
Ciclodextrinas/farmacocinética , Ibuprofeno/farmacocinética , beta-Ciclodextrinas , Animais , Ductos Biliares/metabolismo , Disponibilidade Biológica , Química Farmacêutica , Ciclodextrinas/química , Combinação de Medicamentos , Ibuprofeno/química , Ligadura , Masculino , Ratos , Ratos Wistar , Solubilidade/efeitos dos fármacosRESUMO
The purpose of this study was to examine the viscoelastic properties of topical creams containing various concentrations of microcrystalline cellulose and sodium carboxymethyl cellulose (Avicel(R) CL-611) as a stabilizer. Avicel CL-611 was used at 4 different levels (1%, 2%, 4%, and 6% dispersion) to prepare topical creams, and hydrocortisone acetate was used as a model drug. The viscoelastic properties such as loss modulus (G"), storage modulus (G'), and loss tangent (tan delta) of these creams were measured using a TA Instruments AR 1000 Rheometer and compared to a commercially available formulation. Continuous flow test to determine the yield stress and thixotropic behavior, and dynamic mechanical tests for determining the linear viscosity time sweep data, were performed. Drug release from the various formulations was studied using an Enhancer TM Cell assembly. Formulations containing 1% and 2% Avicel CL-611 had relative viscosity, yield stress, and thixotropic values that were similar to those of the commercial formulation. The elastic modulus (G') of the 1% and 2% formulation was relatively high and did not cross the loss modulus (G"), indicating that the gels were strong. In the commercial formulation, G' increased after preshearing and broke down after 600 seconds. The strain sweep tests showed that for all formulations containing Avicel CL-611, the G' was above G" with a good distance between them. The gel strength and the predominance of G' can be ranked 6% > 4% > 2%. The strain profiles for the 1% and 2% formulations were similar to those of the commercial formulation. The delta values for the 1% and 2% formulations were similar, and the formulations containing 4% Avicel CL-611 had lower delta values, indicating greater elasticity. Drug release from the commercial preparation was fastest compared to the formulations prepared using Avicel CL-611, a correlation with the viscoelastic properties. It was found that viscoelastic data, especially the strain sweep profiles of products containing Avicel CL-611 1% and 2%, correlated with the commercial formulation. Rheological tests that measure the viscosity, yield stress, thixotropic behavior, other oscillatory parameters such as G' and G" are necessary tools in predicting performance of semisolids.
Assuntos
Carboximetilcelulose Sódica/química , Celulose/química , Hidrocortisona/análogos & derivados , Hidrocortisona/química , Bases para Pomadas/química , Administração Tópica , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/efeitos da radiação , Carboximetilcelulose Sódica/metabolismo , Carboximetilcelulose Sódica/efeitos da radiação , Celulose/metabolismo , Celulose/efeitos da radiação , Cromatografia Líquida de Alta Pressão/métodos , Armazenamento de Medicamentos/métodos , Elasticidade/efeitos da radiação , Hidrocortisona/metabolismo , Hidrocortisona/efeitos da radiação , Bases para Pomadas/metabolismo , Bases para Pomadas/efeitos da radiação , Reologia/métodos , Estresse Mecânico , Tecnologia Farmacêutica/instrumentação , Tecnologia Farmacêutica/métodos , Viscosidade/efeitos da radiaçãoRESUMO
The effects of co-formulating amorphous maltodextrins (MDs) and sodium chloride (NaCl), a deliquescent crystalline solid, on moisture sorption, deliquescence point (RH0), and glass transition temperature (Tg) behaviours were investigated. Moisture sorption profiles of binary NaCl:MD mixtures and individual ingredients were generated using controlled relative humidity (RH) desiccators at temperatures from 22 to 50°C and by dynamic vapour sorption (DVS) and dynamic dewpoint sorption (DDS) techniques. Close proximity of MD and NaCl induced synergistic moisture uptake in binary mixtures above a threshold RH, resulting in significantly lower Tgs in binary mixtures compared to individual MDs. The RH0 of NaCl was also lower in the blends. Mixing amorphous MD with crystalline NaCl resulted in synergistic moisture sorption and reduced both Tg and RH0, thus blends were more sensitive to environmental moisture than the individual solids. This has implications for quality control of many formulated powder products.