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1.
Int J Clin Oncol ; 29(6): 706-715, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38679628

ABSTRACT

BACKGROUND AND AIM: The incidence of cancer colon has increased dramatically. In addition, the database lacks a review to analyze the outcomes of surgeries for mid-transverse colon cancer with several recent controversial studies. We aimed to compare the outcomes of extended hemicolectomy versus transverse colectomy for mid-transverse colon cancer. METHOD: PubMed, Scopes, Web of Science and Cochrane Library were searched for eligible studies from inception to 1 December 2022 and a systematic review and meta-analysis were done to detect. RESULTS: According to eligibility criteria, 8 studies (2237 patients) were included in our study. The pooled results of the included studies showed no difference in the 5-year OS, 3-year DFS and 5-year DFS between the two types of surgery (5-year OS, RR = 1.15, 95% CI 0.94-1.39, P = 0.17), (3-year OS, RR = 0.96, 95% CI 0.88-1.06, P = 0.42) and (5-year DFS, RR = 1.21, 95% CI 0.91-1.62, P = 0.20). In addition to that, the recurrence rate and the incidence of complications were similar in the two groups (Recurrence rate, RR = 1.08, 95% CI 0.62-1.89, P = 0.79) and (Complications, RR = 1.07, 95% CI 0.74-1.54, P = 0.72). However, the number of LN harvest and the time of the operation were more in case of extended hemicolectomy. CONCLUSION: Despite harvesting less LN, transverse colectomy has similar oncological outcomes to extended hemicolectomy for mid-transverse colon cancer. In addition to that, there was no significant difference in the incidence of complications between the two surgeries.


Subject(s)
Colectomy , Colonic Neoplasms , Humans , Colectomy/methods , Colectomy/adverse effects , Colon, Transverse/surgery , Colon, Transverse/pathology , Colonic Neoplasms/surgery , Colonic Neoplasms/pathology , Neoplasm Recurrence, Local , Postoperative Complications/epidemiology , Treatment Outcome
2.
J Anaesthesiol Clin Pharmacol ; 40(1): 82-89, 2024.
Article in English | MEDLINE | ID: mdl-38666154

ABSTRACT

Background and Aims: Many strategies are available to prevent spinal-induced hypotension in cesarean section, especially the use of a low dose of spinal anesthesia combined with adjuvants. This study investigated the effect of adding either dexmedetomidine or dexamethasone to the intrathecal bupivacaine-fentanyl mixture on the postoperative analgesia duration, after elective cesarean section. Material and Methods: This prospective, randomized, double-blind study was conducted on 90 full-term parturients undergoing elective cesarean section, who were randomly distributed into three groups. They all received spinal anesthesia with the bupivacaine-fentanyl mixture (2.5 ml), in addition to 0.5 ml normal saline (control group), 5 µg dexmedetomidine dissolved in 0.5 ml normal saline (dexmedetomidine group), or 2 mg dexamethasone (dexamethasone group). The time to the first request of morphine rescue analgesia was recorded, in addition to the total dose of morphine consumed in the first 24 h after surgery, the postoperative numerical rating score (NRS), and maternal and fetal outcomes. Results: As compared to the control group and the dexamethasone group, the use of dexmedetomidine as an additive to the bupivacaine-fentanyl mixture significantly prolonged the time to the first request of rescue analgesia, decreased postoperative morphine consumption, and decreased the pain score 4 and 6 h after surgery. There was an insignificant difference between the control and dexamethasone groups. Conclusion: The use of dexmedetomidine as an additive to bupivacaine-fentanyl mixture in spinal anesthesia for cesarean section prolonged the postoperative analgesia and decreased the postoperative opioid consumption in comparison to the addition of dexamethasone or normal saline.

3.
Afr J Reprod Health ; 28(1): 94-109, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38308556

ABSTRACT

The global disruption created by the Coronavirus Disease 2019 (COVID-19) pandemic in medical education and healthcare institutions is unparalleled. Consequently, it is essential to evaluate the usability of forms of educational technology and to identify their viability and suitability for medical education. The objective of the investigation was to present an assessment of the state of medical education during the COVID-19 epidemic and to identify the obstacles faced by educators while introducing online learning systems for medical students. Two cross-sectional surveys were conducted with 200 medical students and 75 staff members from Saudi Arabia's University of Health. A descriptive method was used to focus on the mechanisms of analysis, foresight, and comprehension of reality. The most significant findings were the obstacles posed by instructors' most urgent requirements for educational technology training and its applications in order to activate distance education in medical education. In addition to a detailed description of the academic and technological concerns and obstacles encountered by students and faculty of health colleges during the pandemic, this report includes a discussion of the pandemic itself. Several prospective recommendations for the use of online and blended learning in health colleges post-pandemic were also made. Additionally, the requirement to activate learning via virtual professional learning groups.


La perturbation mondiale créée par la pandémie de maladie à coronavirus 2019 (COVID-19) dans les établissements d'enseignement médical et de soins de santé est sans précédent. Par conséquent, il est essentiel d'évaluer l'utilisabilité des formes de technologie éducative et d'identifier leur viabilité et leur adéquation à l'enseignement médical. L'objectif de l'enquête était de présenter une évaluation de l'état de l'enseignement médical pendant l'épidémie de COVID-19 et d'identifier les obstacles rencontrés par les éducateurs lors de l'introduction de systèmes d'apprentissage en ligne pour les étudiants en médecine. Deux enquêtes transversales ont été menées auprès de 200 étudiants en médecine et de 75 membres du personnel de l'Université de la Santé d'Arabie Saoudite. Une méthode descriptive a été utilisée pour se concentrer sur les mécanismes d'analyse, de prospective et de compréhension de la réalité. Les résultats les plus significatifs ont été les obstacles posés par les besoins les plus urgents des instructeurs en matière de formation en technologie éducative et ses applications afin d'activer l'enseignement à distance en médecine. éducation. En plus d'une description détaillée des préoccupations et des obstacles académiques et technologiques rencontrés par les étudiants et les professeurs des collèges de santé pendant la pandémie, ce rapport comprend une discussion sur la pandémie elle-même. Plusieurs recommandations prospectives concernant l'utilisation de l'apprentissage en ligne et mixte dans les établissements de santé après la pandémie ont également été formulées. À cela s'ajoute l'obligation d'activer l'apprentissage via des groupes d'apprentissage professionnel virtuels.


Subject(s)
COVID-19 , Education, Medical , Students, Medical , Humans , Cross-Sectional Studies , Prospective Studies , COVID-19/epidemiology , Educational Technology
4.
Int J Nanomedicine ; 19: 209-230, 2024.
Article in English | MEDLINE | ID: mdl-38223883

ABSTRACT

Background: Repaglinide (REP) is an antidiabetic drug with limited oral bioavailability attributable to its low solubility and considerable first-pass hepatic breakdown. This study aimed to develop a biodegradable chitosan-based system loaded with REP-solid lipid nanoparticles (REP-SLNs) for controlled release and bioavailability enhancement via transdermal delivery. Methods: REP-SLNs were fabricated by ultrasonic hot-melt emulsification. A Box-Behnken design (BBD) was employed to explore and optimize the impacts of processing variables (lipid content, surfactant concentration, and sonication amplitude) on particle size (PS), and entrapment efficiency (EE). The optimized REP-SLN formulation was then incorporated within a chitosan solution to develop a transdermal delivery system (REP-SLN-TDDS) and evaluated for physicochemical properties, drug release, and ex vivo permeation profiles. Pharmacokinetic and pharmacodynamic characteristics were assessed using experimental rats. Results: The optimized REP-SLNs had a PS of 249±9.8 nm and EE of 78%±2.3%. The developed REP-SLN-TDDS demonstrated acceptable characteristics without significant aggregation of REP-SLNs throughout the casting and drying processes. The REP-SLN-TDDS exhibited a biphasic release pattern, where around 36% of the drug load was released during the first 2 h, then the drug release was sustained at around 80% at 24 h. The computed flux across rat skin for the REP-SLN-TDDS was 2.481±0.22 µg/cm2/h in comparison to 0.696±0.07 µg/cm2/h for the unprocessed REP, with an enhancement ratio of 3.56. The REP-SLN-TDDS was capable of sustaining greater REP plasma levels over a 24 h period (p<0.05). The REP-SLN-TDDS also reduced blood glucose levels compared to unprocessed REP and commercial tablets (p<0.05) in experimental rats. Conclusion: Our REP-SLN-TDDS can be considered an efficient therapeutic option for REP administration.


Subject(s)
Carbamates , Chitosan , Liposomes , Nanoparticles , Piperidines , Rats , Animals , Rats, Wistar , Lipids/chemistry , Nanoparticles/chemistry , Particle Size , Drug Carriers/chemistry
5.
Oral Maxillofac Surg ; 28(2): 967-974, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38253979

ABSTRACT

PURPOSE: The aim of this study was to evaluate the effect of combining a bone-borne palatal expander (distractor) with a maxillary osteotomy in the treatment of narrowed maxillae in treated cleft palate patients. Few articles in the literature isolated the effects of transpalatal distraction in cleft patients and most either excluded cleft patients or grouped them with non-cleft patients. The hypothesis is that the use of a bone-borne palatal expander in conjunction with a maxillary osteotomy would improve the amount of maxillary expansion at the anterior segment with less tipping of the segments and provide a harmonious arch form. METHODS: We studied four patients above 14 years of age with repaired cleft palate and progressive anterior constriction of the arch. All patients received a bone-borne distractor (UNI-Smile Distractor, Titamed, Belgium) combined with a LeFort I level osteotomy without pterygomaxillary disjunction. Dental models and CBCT measurements were used to analyze the skeletal and dental effects of the intervention. RESULT: All the patients who completed the trial had satisfactory expansion and normalization of the maxillary arch form. The average increase in the intercanine distance was 12.9 mm while the average increase in the intermolar distance was 7.2 mm. No significant change in molar inclination or buccal bone thickness was observed. CONCLUSION: The use of bone-borne palatal expanders aided by a maxillary osteotomy (transpalatal distraction) in treated cleft palate patients can provide a harmonious arch form in adolescent and adult patients. This trial was registered in the clinical trials registry with the ID NCT03837652 on February 12, 2019.


Subject(s)
Cleft Palate , Osteogenesis, Distraction , Palatal Expansion Technique , Adolescent , Female , Humans , Male , Cleft Palate/surgery , Cleft Palate/diagnostic imaging , Cone-Beam Computed Tomography , Maxilla/surgery , Maxilla/abnormalities , Osteogenesis, Distraction/methods , Osteogenesis, Distraction/instrumentation , Osteotomy, Le Fort/methods , Palatal Expansion Technique/instrumentation
6.
Talanta ; 269: 125498, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38056419

ABSTRACT

A high-throughput therapeutic monitoring method was developed for repaglinide (RPG) in diabetic patients, combining parallel artificial liquid membrane extraction (PALME) with ultraperformance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). PALME was performed using a 96-well donor plate comprising a donor solution containing a plasma sample, 50 mM phosphate buffer (pH = 8.0), and cetirizine (CTZ) as internal standard. A polypropylene (PP) porous membrane served as a selective support for the liquid membrane (SLM), preventing nonspecific binding produced by other membranes. The extraction was accomplished across SLM made of PP membrane with dodecyl acetate and 1 % trioctylamine (w/w), and the acceptor solution comprised DMSO and 200 mM formic acid (50:50, v/v). The simple workflow for PALME provided analyte enrichment, highly efficient sample cleanup, high throughput analysis, and excellent reproducibility. Method validation met FDA criteria, with a linear plasma calibration range (0.1-100 ng mL-1, r = 0.9995) and a lower limit of quantitation (LLOQ) of 0.1 ng mL-1. Recovery results at 98.9 % affirmed method reliability. The ability to analyze 198 samples per hour, coupled with a reduced amount of solvents, underscores the method's high throughput and eco-friendly profile. The PALME-UPLC-ESI-MS/MS method was successfully applied to therapeutic drug monitoring of RPG in diabetic patients following 2 mg RPG tablet administration, establishing its effectiveness.


Subject(s)
Diabetes Mellitus , Tandem Mass Spectrometry , Humans , Tandem Mass Spectrometry/methods , Reproducibility of Results , Chromatography, High Pressure Liquid/methods , Membranes, Artificial
7.
Polymers (Basel) ; 15(19)2023 Oct 04.
Article in English | MEDLINE | ID: mdl-37836040

ABSTRACT

Current fundamental electrochemical research shows the potential of utilizing polymeric nanostructured materials as ion-to-electron transducers. In this paper, aniline was polymerized in the presence of TiO2 and CuO nanoparticles to yield a bimetallic/PANI nanocomposite. It was applied as a transducer in a carbon paste electrode for the potentiometric determination of vildagliptin in the presence of 18-crown-6-ether as a recognition element. The electrode's potentiometric performance was studied according to the IUPAC guidelines. It exhibited a wide linearity range of 1 × 10-2 M to 1 × 10-8 M, remarkable sensitivity (LOD of 4.5 × 10-9 M), and a fast response time of 10 s ± 1.3. The sensor did not show any potential drift due to the absence of the water layer between the carbon paste and the metallic conductor. This endowed the sensor with high stability and a long lifetime, as 137 days passed without the need to change the carbon paste surface. The electrode was utilized for the determination of the concentration of vildagliptin in bulk, pharmaceutical tablets, and human plasma, with average recovery ranging from 97.65% to 100.03%.

8.
BMC Pregnancy Childbirth ; 23(1): 486, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37393228

ABSTRACT

BACKGROUND: Cervical pregnancy is a rare type of ectopic pregnancy. The management of cervical pregnancy is challenging because of the rarity of the condition, late presentation, which is associated with increased risk of failed medical treatment, and excessive post-evacuation bleeding that may require hysterectomy. There is no good evidence in the literature regarding the pharmacological management of living cervical ectopic pregnancy of more than 9 + 0 weeks of gestation, and there is no standard protocol on methotrexate doses in these cases. CASE PRESENTATION: We present this case to describe a concomitant medical and surgical management of a living 11 + 5 weeks cervical pregnancy. The initial beta-human chorionic gonadotropins (ß-hCG) serum level was 108,730 IU/L. The patient received 60 mg of methotrexate intra-amniotically followed by another dose of 60 mg of methotrexate intramuscularly 24 h later. Fetal heartbeats stopped on day 03. On day 07, the ß-hCG was 37,397 IU/L. On day 13, the patient had evacuation of the remaining products of conception with the insertion of an intracervical Foley catheter to minimize the bleeding. On day 34, the ß-hCG was negative. CONCLUSION: The concomitant use of methotrexate to induce fetal demise along with surgical evacuation may be considered in the management of advanced cervical pregnancy to avoid excessive blood loss, and ultimately hysterectomy.


Subject(s)
Methotrexate , Pregnancy, Ectopic , Female , Pregnancy , Humans , Methotrexate/therapeutic use , Chorionic Gonadotropin, beta Subunit, Human , Pregnancy, Ectopic/drug therapy , Pregnancy, Ectopic/surgery , Fetus , Fertilization
9.
Int J Mol Sci ; 24(10)2023 May 18.
Article in English | MEDLINE | ID: mdl-37240319

ABSTRACT

Elucidation of the redox pathways in severe coronavirus disease 2019 (COVID-19) might aid in the treatment and management of the disease. However, the roles of individual reactive oxygen species (ROS) and individual reactive nitrogen species (RNS) in COVID-19 severity have not been studied to date. The main objective of this research was to assess the levels of individual ROS and RNS in the sera of COVID-19 patients. The roles of individual ROS and RNS in COVID-19 severity and their usefulness as potential disease severity biomarkers were also clarified for the first time. The current case-control study enrolled 110 COVID-19-positive patients and 50 healthy controls of both genders. The serum levels of three individual RNS (nitric oxide (NO•), nitrogen dioxide (ONO-), and peroxynitrite (ONOO-)) and four ROS (superoxide anion (O2•-), hydroxyl radical (•OH), singlet oxygen (1O2), and hydrogen peroxide (H2O2)) were measured. All subjects underwent thorough clinical and routine laboratory evaluations. The main biochemical markers for disease severity were measured and correlated with the ROS and RNS levels, and they included tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), the neutrophil-to-lymphocyte ratio (NLR), and angiotensin-converting enzyme 2 (ACE2). The results indicated that the serum levels of individual ROS and RNS were significantly higher in COVID-19 patients than in healthy subjects. The correlations between the serum levels of ROS and RNS and the biochemical markers ranged from moderate to very strongly positive. Moreover, significantly elevated serum levels of ROS and RNS were observed in intensive care unit (ICU) patients compared with non-ICU patients. Thus, ROS and RNS concentrations in serum can be used as biomarkers to track the prognosis of COVID-19. This investigation demonstrated that oxidative and nitrative stress play a role in the etiology of COVID-19 and contribute to disease severity; thus, ROS and RNS are probable innovative targets in COVID-19 therapeutics.


Subject(s)
COVID-19 , Oxygen , Humans , Female , Male , Reactive Oxygen Species/metabolism , Hydrogen Peroxide/metabolism , Case-Control Studies , Reactive Nitrogen Species/metabolism , Nitric Oxide , Biomarkers , Patient Acuity
10.
Indian J Anaesth ; 67(2): 186-193, 2023 Feb.
Article in English | MEDLINE | ID: mdl-37091455

ABSTRACT

Background and Aims: Ketamine and dexmedet omidine have neuroprotective effects that may reduce the occurrence of postoperative cognitive dysfunction (POCD) when they are used by intravenous infusion in geriatric patients scheduled for cataract extraction. Methods: Ninety patients aged 65-85 years old, ASA physical status II and III, and scheduled for cataract extraction under peribulbar block were randomly distributed equally among three groups: control group, in which patients received normal saline; ketamine group, in which patients received 0.3 mg/kg/h of ketamine; and dexmedetomidine group, in which patients received 0.5 µg/kg/h of dexmedetomidine. Medications were administrated by intravenous infusion and started 10 min before the surgery and continued throughout the duration of surgery. The analysed parameters included the incidence of POCD (primary outcome) through composite score of neuropsychological testing at one week and 3 months after surgery, postoperative pain score, postoperative sedation score, changes in haemodynamic parameters, changes in intraocular pressure, and incidence of complications. Results: In comparison with control group, ketamine and dexmedetomidine groups exhibited a significant decline in number of patients who developed POCD (P < 0.0001), a decrease in the postoperative pain score 4 h after surgery (P = 0.038), and an increase in the postoperative Ramsay sedation Score (P = 0.0002, 0.0003, and 0.011), without significant changes in the vital parameters, intraocular tension, or incidence of complications. Ketamine and dexmedetomidine groups were comparable. Conclusion: Intravenous administration of ketamine or dexmedetomidine in elderly patients undergoing cataract surgery under peribulbar anesthesia significantly decreases the incidence of POCD.

11.
Micromachines (Basel) ; 14(3)2023 Feb 27.
Article in English | MEDLINE | ID: mdl-36984971

ABSTRACT

This study aims to investigate the magnetohydrodynamic flow induced by a moving surface in a nanofluid and the occurrence of suction and solar radiation effects using the Buongiorno model. The numerical findings are obtained using MATLAB software. The effects of various governing parameters on the rates of heat and mass transfer along with the nanoparticles concentration and temperature profiles are elucidated graphically. Non-unique solutions are discovered for a specific variation of the shrinking strength. The temporal stability analysis shows that only one of them is stable as time passes. Furthermore, raising the Brownian motion parameter reduces both the local Sherwood number and the local Nusselt number for both solutions. It is also observed that increasing the thermophoresis parameter reduces the rate of heat transfer, whereas the opposite trend is observed for the rate of mass transfer.

13.
J Am Med Inform Assoc ; 30(4): 656-667, 2023 03 16.
Article in English | MEDLINE | ID: mdl-36575995

ABSTRACT

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) resource allocation tools are currently lacking. We developed machine learning (ML) models for predicting COVID-19 patients at risk of receiving ECMO to guide patient triage and resource allocation. MATERIAL AND METHODS: We included COVID-19 patients admitted to intensive care units for >24 h from March 2020 to October 2021, divided into training and testing development and testing-only holdout cohorts. We developed ECMO deployment timely prediction model ForecastECMO using Gradient Boosting Tree (GBT), with pre-ECMO prediction horizons from 0 to 48 h, compared to PaO2/FiO2 ratio, Sequential Organ Failure Assessment score, PREdiction of Survival on ECMO Therapy score, logistic regression, and 30 pre-selected clinical variables GBT Clinical GBT models, with area under the receiver operator curve (AUROC) and precision recall curve (AUPRC) metrics. RESULTS: ECMO prevalence was 2.89% and 1.73% in development and holdout cohorts. ForecastECMO had the best performance in both cohorts. At the 18-h prediction horizon, a potentially clinically actionable pre-ECMO window, ForecastECMO, had the highest AUROC (0.94 and 0.95) and AUPRC (0.54 and 0.37) in development and holdout cohorts in identifying ECMO patients without data 18 h prior to ECMO. DISCUSSION AND CONCLUSIONS: We developed a multi-horizon model, ForecastECMO, with high performance in identifying patients receiving ECMO at various prediction horizons. This model has potential to be used as early alert tool to guide ECMO resource allocation for COVID-19 patients. Future prospective multicenter validation would provide evidence for generalizability and real-world application of such models to improve patient outcomes.


Subject(s)
COVID-19 , Critical Illness , Humans , Critical Illness/therapy , Retrospective Studies , COVID-19/therapy , Organ Dysfunction Scores , Intensive Care Units
14.
Nutrients ; 14(24)2022 Dec 15.
Article in English | MEDLINE | ID: mdl-36558489

ABSTRACT

Vitamin D is among the increasingly consumed dietary supplements during the COVID-19 pandemic. It plays a regulatory role in the immune system and moderates the renin-angiotensin system, which is implicated in infection pathogenesis. However, the investigation of serum levels of vitamin D3 forms and their relative ratios in COVID-19 patients is worth investigation to understand the impacts of disease severity. Hence, we investigated the serum levels of vitamin D3 (cholecalciferol) and its metabolites (calcifediol and calcitriol), in addition to their relative ratios and correlations with angiotensin-converting enzyme 2 (ACE2), interleukin-6 (Il-6), and neutrophil-lymphocyte ratio (NLR) in COVID-19 patients compared with healthy controls. Oropharyngeal specimens were collected from the study subjects for polymerase chain reaction testing for COVID-19. Whole blood samples were obtained for blood count and NLR testing, and sera were used for the analysis of the levels of the vitamin and its metabolites, ACE2, and IL-6. We enrolled 103 patients and 50 controls. ACE2, Il-6, and NLR were significantly higher in the patients group (72.37 ± 18.67 vs. 32.36 ± 11.27 U/L, 95.84 ± 25.23 vs. 2.76 ± 0.62 pg/mL, and 1.61 ± 0.30 vs. 1.07 ± 0.16, respectively). Cholecalciferol, calcifediol, and calcitriol were significantly lower in patients (18.50 ± 5.36 vs. 29.13 ± 4.94 ng/mL, 14.60 ± 3.30 vs. 23.10 ± 3.02 ng/mL, and 42.90 ± 8.44 vs. 65.15 ± 7.11 pg/mL, respectively). However, their relative ratios were normal in both groups. Levels of the vitamin and metabolites were strongly positively, strongly negatively, and moderately negatively correlated with ACE2, Il-6, and NLR, respectively. COVID-19 infection severity is associated with a significant decrease in vitamin D3 and its metabolites in a parallel pattern, and with a significant increase in ACE2, Il-6, and NLR. Higher levels of vitamin D and its metabolites are potentially protective against severe infection.


Subject(s)
COVID-19 , Cholecalciferol , Humans , Angiotensin-Converting Enzyme 2 , Calcifediol , Calcitriol , Cholecalciferol/blood , COVID-19/diagnosis , COVID-19 Testing , Interleukin-6 , Pandemics , Patient Acuity , Prognosis , Vitamin D , Vitamins
15.
Pharmaceutics ; 14(12)2022 Nov 24.
Article in English | MEDLINE | ID: mdl-36559086

ABSTRACT

Tadalafil (TAD) is a poorly soluble, phosphodiesterase inhibitor used to treat erectile dysfunction. The primary goal of this project was to prepare nano-emulsions using ultrasonic technology to address TAD bioavailability concerns. The Box−Behnken design was employed to find prominent correlations between factors impacting the sono-emulsification process. The emulsifier concentration, amplitude level, and ultrasonication time were the independent factors, whereas the average droplet size (ADS) and polydispersity index (PDI) were designated as the response variables. TAD-loaded nano-emulsions (93−289 nm) were generated and the emulsifier concentration showed a crucial role in directing emulsion droplet size. The model desirability function was utilized to optimize a nano-emulsion with a small ADS (99.67 ± 7.55 nm) and PDI (0.45 ± 0.04) by adjusting the emulsifiers concentration, amplitude level, and ultrasonication time at 9.85%, 33%, 49 s, respectively. The optimized nano-emulsions did not demonstrate any precipitation or phase separation after stability stress tests. TAD jellies were formulated based on the optimized nano-emulsion and subjected to in vitro evaluation for physical characteristics; TAD content, pH, spreadability, viscosity, syneresis, and taste-masking ability. An optimized nano-emulsion-based jelly (NEJ) formulation showed more than 96% drug dissolution in 30 min relative to 14% for the unprocessed TAD. In vivo assessment of NEJ in experimental rats demonstrated a significant enhancement (p < 0.05) of TAD bioavailability with an AUC0−24h of 2045 ± 70.2 vs. 259.9 ± 17.7 ng·h·mL−1 for the unprocessed TAD. Storage stability results revealed that NEJ remained stable with unremarkable changes in properties for 3 months. Overall, NEJ can be regarded as a successful therapeutic option for TAD administration with immediate-release properties and improved bioavailability.

17.
Saudi Pharm J ; 30(8): 1143-1152, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36164574

ABSTRACT

The current study coupled fabric phase sorptive extraction (FPSE) with ultraperformance liquid chromatography method with electrospray ionization and tandem mass detection (UPLC-ESI-MS/MS) for fast and sensitive determination of tadalafil (TAD) in a bioequivalence study. Fabric phase sorptive extraction allowed direct extraction of TAD from the sample matrix with improved selectivity, repeatability, and recoveries. A sol-gel Carbowax 20 M (CX-20 M) coated FPSE membrane revealed the best extraction efficiency for TAD because of its strong affinity for analytes via intermolecular interactions, high mass transfer rate to FPSE membrane, and high permeability. An automated multiple reaction monitoring (MRM) optimizer was employed for the best selection of the precursor and product ions, ion breakdown profile, the fine adjustment of the fragmentor voltages for each precursor ions, and the collision energies for the product ions. The chromatographic separation was conducted using a mobile phase A: 5.0 mM ammonium acetate with 0.1 % formic acid in water and mobile phase B: formic acid (0.1%) in acetonitrile in ratio (55:45, v/v) through isocratic elution mode on an Agilent EclipsePlus C18 (50 × 2.1 mm, 1.8 µm) column and the flow rate was adjusted at 0.4 mL min-1. The total run time per sample was 1.0 min. The method was validated by FDA standards for bioanalytical method validation over a concentration range of 0.1-100 ng mL-1 with a correlation coefficient of 0.9993 and the lower limit of quantitation (LLOQ) was 0.1 ng mL-1 in rat plasma. Intra- and inter-assay precision (%RSD) were lower than 4.1% and accuracy (%RE) was within 2.4%. The developed FPSE-UPLC-ESI-MS/MS method was effectively used in a randomized, two-way, single-dose, crossover study to compare the bioequivalence of two TAD formulations from different companies in male rats and verified to be bioequivalent.

18.
Pharmaceutics ; 14(9)2022 Sep 12.
Article in English | MEDLINE | ID: mdl-36145675

ABSTRACT

This research aimed to develop innovative self-nanoemulsifying chewable tablets (SNECT) to increase oral bioavailability of tadalafil (TDL), a nearly insoluble phosphodiesterase-5 inhibitor. Cinnamon essential oil, PEG 40 hydrogenated castor oil (Cremophor® RH 40), and polyethylene glycol 400 served as the oil, surfactant, and cosurfactant in the nanoemulsifying system, respectively. Primary liquid self-nanoemulsifying delivery systems (L-SNEDDS) were designed using phase diagrams and tested for dispersibility, droplet size, self-emulsifying capability, and thermodynamic stability. Adsorption on a carrier mix of silicon dioxide and microcrystalline cellulose was exploited to solidify the optimum L-SNEDDS formulation as self-nanoemulsifying granules (SNEG). Lack of crystalline TDL within the granules was verified by DSC and XRPD. SNEG were able to create a nanoemulsion instantaneously (165 nm), a little larger than the original nanoemulsion (159 nm). SNECT were fabricated by compressing SNEG with appropriate excipients. The obtained SNECT retained their quick dispersibility dissolving 84% of TDL within 30 min compared to only 18% dissolution from tablets of unprocessed TDL. A pharmacokinetic study in Sprague−Dawley rats showed a significant increase in Cmax (2.3-fold) and AUC0−24 h (5.33-fold) of SNECT relative to the unprocessed TDL-tablet (p < 0.05). The stability of TDL-SNECT was checked against dilutions with simulated GI fluids. In addition, accelerated stability tests were performed for three months at 40 ± 2 °C and 75% relative humidity. Results revealed the absence of obvious changes in size, PDI, or other tablet parameters before and after testing. In conclusion, current findings illustrated effectiveness of SNECT to enhance TDL dissolution and bioavailability in addition to facilitating dose administration.

19.
Micromachines (Basel) ; 13(7)2022 Jun 30.
Article in English | MEDLINE | ID: mdl-35888878

ABSTRACT

Thermophoresis represents one of the most common methods of directing micromachines. Enhancement of heat transfer rates are of economic interest for micromachine operation. This study aims to examine the heat transfer enhancement within the shell and tube latent heat thermal storage system (LHTSS) using PCMs (Phase Change Materials). The enthalpy-porosity approach is applied to formulate the melting situation and various shapes of inner heated fins are considered. The solution methodology is based on the Galerkin finite element analyses and wide ranges of the nanoparticle volume fraction are assumed, i.e., (0% ≤ φ ≤ 6%). The system entropy and the optimization of irreversibility are analyzed using the second law of the thermodynamics. The key outcomes revealed that the flow features, hexagonal entropy, and melting rate might be adjusted by varying the number of heated fins. Additionally, in case 4 where eight heated fins are considered, the highest results for the average liquid percentage are obtained.

20.
Sci Rep ; 12(1): 11521, 2022 Jul 07.
Article in English | MEDLINE | ID: mdl-35798795

ABSTRACT

The current paper discusses the numerical simulation results of the NePCM melting process inside an annulus thermal storage system. The TES system consists of a wavy shell wall and a cylindrical tube equipped with three fins. The enthalpy-porosity method was utilized to address the transient behavior of the melting process, while the Galerkin FE technique was used to solve the system governing equations. The results were displayed for different inner tube positions (right-left-up and down), inner cylinder rotation angle (0 ≤ α ≤ 3π/2), and the nano-additives concentration (0 ≤ ϕ ≤ 0.04). The findings indicated that high values of nano-additives concentration (0.4), bigger values of tube rotation angle (3π/2), and location of the tube at the lower position accelerated the NePCM melting process.

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