Oral Route Of Administration Research Articles

Towards more translatable research: Exploring alternatives to gavage as the oral administration route of vaccines in rodents for improved animal welfare and human relevance.

Towards more translatable research: Exploring alternatives to gavage as the oral administration route of vaccines in rodents for improved animal welfare and human relevance.

Efficacy and Safety of S1P1 Receptor Modulator Drugs for Patients with Moderate-to-Severe Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that negatively impacts patients' quality of life. In the last decades, the therapeutic options available for the management of patients with moderate to severe UC have increased significantly, including not only biological drugs but also small molecules. However, there is a persistent need to develop new drugs that act on new targets while minimizing the risk of adverse events. Sphingosine-1-phosphate (S1P) is a membrane-derived lysophospholipid. The S1P gradient between tissues and the circulatory system has a key role in regulating the trafficking of immune cells as autoreactive B and T lymphocytes. S1P receptor modulators could be a safe and efficacious alternative mechanism for reducing inflammation in immune-mediated disorders, including UC, by reducing lymphocyte egress from the lymph nodes to the bloodstream. Several S1P receptor modulators have been developed and tested in UC. Ozanimod is already approved by Food and Drug Administration (FDA) and European Medical Agency (EMA), while etrasimod and VTX002 are still under approval. Oral administration route, rapidity and reliable safety profile are the main advantages of this class of drugs. The aim of this review is to summarize the available evidence for the efficacy, safety, and pharmacokinetics of ozanimod, etrasimod, and VTX002 in UC.

Dose- and application route-dependent effects of betahistine on behavioral recovery and neuroplasticity after acute unilateral labyrinthectomy in rats.

Betahistine is widely used for the treatment of various vestibular disorders. However, the approved oral administration route and maximum daily dose are evidently not effective in clinical trials, possibly due to a major first-pass metabolism by monoamine oxidases (MAOs). The current study aimed to test different application routes (i.v./s.c./p.o.), doses, and concurrent medication (with the MAO-B inhibitor selegiline) for their effects on behavioral recovery and cerebral target engagement following unilateral labyrinthectomy (UL) in rats. Sixty rats were subjected to UL by transtympanic injection of bupivacaine/arsanilic acid and assigned to five treatment groups: i.v. low-dose betahistine (1 mg/kg bid), i.v. high-dose betahistine (10 mg/kg bid), p.o. betahistine (1 mg/kg bid)/selegiline (1 mg/kg once daily), s.c. betahistine (continuous release of 4.8 mg/day), and i.v. normal saline bid (sham treatment; days 1-3 post-UL), respectively. Behavioral testing of postural asymmetry, nystagmus, and mobility in an open field was performed seven times until day 30 post-UL and paralleled by sequential cerebral [18F]-FDG-μPET measurements. The therapeutic effects of betahistine after UL differed in extent and time course and were dependent on the dose, application route, and selegiline co-medication: Postural asymmetry was significantly reduced on 2-3 days post-UL by i.v. high-dose and s.c. betahistine only. No changes were observed in the intensity of nystagmus across groups. When compared to sham treatment, movement distance in the open field increased up to 5-fold from 2 to 30 days post-UL in the s.c., i.v. high-dose, and p.o. betahistine/selegiline groups. [18F]-FDG-μPET showed a dose-dependent rCGM increase in the ipsilesional vestibular nucleus until day 3 post-UL for i.v. high- vs. low-dose betahistine and sham treatment, as well as for p.o. betahistine/selegiline and s.c. betahistine vs. sham treatment. From 1 to 30 days post-UL, rCGM increased in the thalamus bilaterally for i.v. high-dose betahistine, s.c. betahistine, and p.o. betahistine/selegiline vs. saline treatment. Betahistine has the potential to augment the recovery of dynamic deficits after UL if the administration protocol is optimized toward higher effective plasma levels. This may be achieved by higher doses, inhibition of MAO-based metabolism, or a parenteral route. In vivo imaging suggests a drug-target engagement in central vestibular networks.

Formulation Development of Tolperisone Hydrochloride Film Coated Tablet

Among all the different routes of administration, oral route of administration continues to be the most preferred route due to various advantages including ease of ingestion, avoidance of pain, versatility and most importantly patient compliance. Likewise, among all dosage forms tablet is the most popular dosage form existing today because of its convenience of self-administration, compactness and easy manufacturing. Sometimes immediate onset of action is considered obligatory immediate release tablets are the final option. Recently immediate release tablets have started gaining popularity and acceptance as a drug delivery system, mainly because they are easy to administer and lead to better patient compliance. In the present work, we engage in discussion about formulation, development, and evaluation of immediate release tablets. An immediate release dosage form allows a manufacturer to extend market exclusivity. They are also a tool for expanding markets, extending product life cycles and generating opportunities. pharmaceutical products designed for oral delivery and currently available on the prescription and over-the-counter markets are mostly the immediate release type, which are designed for immediate release of drug for rapid absorption. Tolperisone Hydrochloride Film Coated Tablets 50 mg was prepared using various excipients listed as in formula. The tablets were prepared by wet granulation method using concave plane punch on multi-station compression machine. The formulations were evaluated for their physical characteristics like thickness, hardness and friability, weight variation, content uniformity study was carried out. Evaluated for chemical analysis like Assay, disintegration and dissolution. In-vitro comparative dissolution study was performed with the help of U.S.P dissolution test apparatus-II with 900 ml of 0.1 N HCL, Acetate buffer pH 4.5 & 0.1 M HCL Acid at the 75 rpm for 45min.

Anti‑inflammatory effect of metformin against an experimental model of LPS‑induced cytokine storm.

Cytokine storm is one of the leading causes of death in patients with COVID-19. Metformin has been shown to inhibit the action of a wide range of proinflammatory cytokines such as IL-6, and TNF-α which may ultimately affect cytokine storm due to Covid-19. The present study analyzed the anti-inflammatory effect of oral and intraperitoneal (IP) metformin administration routes in a mouse model of lipopolysaccharide (LPS)-induced cytokine storm. A total of 60 female BALB/c mice were randomly assigned to one of six groups: i) Control; ii) LPS model; iii) oral saline + LPS; iv) oral metformin + LPS; v) IP saline + LPS; and vi) IP metformin + LPS. Metformin or saline were administered to the mice for 30 days, after which an IP injection of 0.5 mg/kg LPS induced a cytokine storm in the five treatment groups. Mice were sacrificed and serum cytokine levels were measured. Pretreatment of mice with either oral or IP metformin significantly reduced the increase in IL-1, IL-6 and TNF-α following LPS injection. Both metformin administration routes significantly reduced IL-1 and TNF-α levels, although IP metformin appeared to be significantly more effective at reducing IL-6 levels compared with oral metformin. Neither the oral or IP route of administration of metformin demonstrated a significant effect on IL-17 levels. Based on its ability to suppress the proinflammatory LPS-induced cytokine storm, metformin may have future potential benefits in ameliorating human diseases caused by elevated cytokine levels.

Prescription Patterns of Analgesic Drugs in the Management of Pain Among Palliative Care Patients at a Tertiary Hospital in Oman: A Retrospective Observational Study.

Objectives Analgesic drugs are commonly used to alleviate the pain experienced by palliative care (PC) patients. Thus, we sought to determine the prescription patterns of analgesic drugs in the management of pain among haematology and oncology palliative care patients at Sultan Qaboos University Hospital (SQUH) and then see if they were following the World Health Organization (WHO) guidelines. Methods A retrospective observational cross-sectional study was conducted, and adult PC patients prescribed analgesics for pain relief between January 2018 and January 2021 at SQUH constituted the sample. Data were collected from patients' electronic medical records using the SQUH TrakCare system. The data was then presented descriptively using graphs and tables. Results Data from 200 PC patients were analyzed. Breast cancer was the most common malignancy, with 73 (36.5%) patients diagnosed with it. Severe pain was the most reported degree of pain, with exactly 100 (50.0%) patients experiencing it. More patients experienced mild pain than moderate pain. Opioids were the most prescribed analgesics, followed by analgesics and antipyretics, anticonvulsants, and finally non-steroidal anti-inflammatory drugs (NSAIDs). Paracetamol was the most prescribed analgesic for pain overall, with 127 (63.5%) patients utilizing it. For severe pain, morphine was the most prescribed analgesic, with 65.0% of patients using it. Fentanyl and pregabalin, the strongest two analgesics, increased in prescription for severe pain compared to mild and moderate pain, with both being prescribed to 23.0% of patients suffering from severe pain. The oral route of administration was the most prescribed, with 128 (64.0%) utilizing it. Conclusion This study showed the prescription patterns of analgesic drugs for palliative care patients at SQUH. The findings were similar to those of other studies, though there were some differences. The prescription patterns of analgesic drugs prescribed for the various pain levels among PC patients were found to be in accordance with the WHO guidelines.

Formulation of Dispersible Ayurvedic Kadha Tablet for the Management of Cold and Cough

The term “Ayurveda” combines the Sanskrit words ayur (life) and veda (science or knowledge). It is one of the traditional medicinal systems, with an established history of many centuries. Indian herbs, which are widely used in the preparation of Ayurvedic medicines in the form of Kadha to control various respiratory disorders such as, cough, cold and flu. In a traditional Kadha (decoction) preparation, the entire process is done manually Such as boiling, filtering and mixing of medicinal herbs and the aim of this research work was to skip all such manually process. The oral route of drug administration is most extensively used due to the obvious ease of administration. Dispersible tablets are a vital tool in keeping our children and elderly population healthy. Their ease of use and accurate dosing allow higher patient compliance and more reliable therapeutic effects. Medicinal plants and parts as like Tulsi (Rama-Tulsi) (Ocimum Sanctum Linn, family Lamiaceae), Ginger (Zingiber officinale, family Zingiberaceae), Clove (Syzygium aromaticum, family myrtaceae) and Turmeric (Curcuma longa, family Zingiberaceae) were used as a model drug. Phytochemicals present in these herbs, which have significant potential to heal cold and cough. The phytochemicals present in these herbs possess significant anti-inflammatory property. In order to determine the most effective type and optimal amount of superdisintegrants for dispersible tablets different formulation were evaluated. Wet granulation and direct compression methods were tried to develop dispersible tablet. Due to higher moisture in the granules the wet granulation method was not carried out further in the study and direct compress method was selected. Prepared tablets were tested for Appearance, Weight variation, Thickness, Friability (%), Hardness (kg/cm2 ), Disintegration time and IR spectroscopic analysis and finally for six months of stability studies at room temperature, 30ºC/60% RH and at 45ºC/75% RH. Sodium Starch Glycolate was superior to the other disintegrants and the non-fractionated granulation gave adequate dispersion. The ideal concentration was 1.33 % Sodium Starch Glycolate was used for the dispersible tablets

Hypoxia Associated With Dihydropyridine Calcium Channel Inhibitors: A Pharmacovigilance Study in VigiBase.

Due to their negative effects on hypoxic pulmonary vasoconstriction, dihydropyridine calcium channel inhibitors (DCCIs) can lead to hypoxia in patients with a pulmonary shunt. To date, only preclinical studies and case reports have focused on this potential adverse drug reaction. We aimed to assess the reporting association between DCCIs and hypoxia using the World Health Organization pharmacovigilance database (VigiBase). We performed a disproportionality analysis to evaluate the strength of the reporting association between i.v. clevidipine and nicardipine, thought to be a surrogate of patients in the intensive care unit, and hypoxia. The information component and the lower end of its 95% credibility interval were used to evaluate disproportionality. A description of the cases was made. Secondary outcomes included the association between all DCCIs and hypoxia compared with other treatments with similar indications, urapidil and labetalol, regardless of the route of administration. Association between oral nicardipine and hypoxia was also searched. A statistically significant signal of hypoxia was found for intravenous clevidipine and nicardipine. The time to onset was reported with a median of 2 days (interquartile range 1.5-4.5). Four dechallenges were performed with intravenous nicardipine, leading to the resolution of the symptoms. Regardless of the route of administration, a signal of hypoxia was also found for nimodipine but not for other drugs, including comparators. For nicardipine no signal of hypoxia was found with the oral route of administration. Our pharmacovigilance database analysis showed a significant association between the use of intravenous DCCIs and hypoxia.

Optimization of Potential Nanoemulgels for Boosting Transdermal Glimepiride Delivery and Upgrading Its Anti-Diabetic Activity.

Transdermal drug delivery has been widely adopted as a plausible alternative to the oral route of administration, especially for drugs with poor systemic bioavailability. The objective of this study was to design and validate a nanoemulsion (NE) system for transdermal administration of the oral hypoglycemic drug glimepiride (GM). The NEs were prepared using peppermint/bergamot oils as the oil phase and tween 80/transcutol P as the surfactant/co-surfactant mixture (Smix). The formulations were characterized using various parameters such as globule size, zeta potential, surface morphology, in vitro drug release, drug-excipient compatibility studies, and thermodynamic stability. The optimized NE formulation was then incorporated into different gel bases and examined for gel strength, pH, viscosity, and spreadability. The selected drug-loaded nanoemulgel formulation was then screened for ex vivo permeation, skin irritation, and in vivo pharmacokinetics. Characterization studies revealed the spherical shape of NE droplets with an average size of ~80 nm and a zeta potential of -11.8 mV, which indicated good electrokinetic stability of NE. In vitro release studies revealed enhanced drug release from the NE formulation compared to the plain drug. GM-loaded nanoemulgel showed a 7-fold increment in drug transdermal flux compared to plain drug gel. In addition, the GM-loaded nanoemulgel formulation did not elicit any signs of inflammation and/or irritation on the applied skin, suggesting its safety. Most importantly, the in vivo pharmacokinetic study emphasized the potential of nanoemulgel formulation to potentiate the systemic bioavailability of GM, as manifested by a 10-fold rise in the relative bioavailability compared to control gel. Collectively, transdermal NE-based GM gel might represent a promising alternative to oral therapy in the management of diabetes.

Cissampelos pareira ethanolic extract modulates hormonal indices, lipid profile, and oxidative parameters in transient infertility-induced female albino rats

Cissampelos pareira is a medicinal plant with conflicting local claims regarding its usage in the management of fertility disorder. This study investigates the effect of the ethanolic extract of C. pareira on fertility indices in female albino rats. Ethanolic extract of C. pareira was administered orally for 14 days to female rats placed in different groups. Levonorgestrel (0.14mg/g) was orally administered to certain rat groups for 7 days to induce transient infertility before other treatments. The rats were sacrificed at the completion of their respective oral administration route. Blood samples were collected through cardiac puncture for hormonal and lipid profiling, which were analysed using commercial standard enzyme-linked immunosorbent assay (ELISA) kit. Organs were harvested for the assessment of oxidative parameters. Phytochemical screening reveals the presence of alkaloid, saponin, glycoside, tannin, steroid and flavonoid in the extract. The extract has no significant effect on progesterone, significantly reduced testosterone (p<0.05), but increased prolactin and estradiol concentrations (p<0.05). No significant hormonal difference in groups pre-administered levonorgestrel. The extract significantly elevated serum triglyceride, but reduced cholesterol level (p<0.05), even in groups pre-administered with levonorgestrel. The extract significantly reduced H2O2 and SOD activities (p<0.05) in the ovary and kidney respectively. Following levonorgestrel pre- administration, the extract significantly reduced H2O2 and GSH in the liver and kidney, elevated SOD activities in the liver, ovary and brain (p<0.05). This study demonstrated the antifertility properties of the ethanolic extract of Cissampelos pareira, shown by its effects of the hormonal and lipid profile, with moderate antioxidant effect.

Critical Strategies for Drug Precipitation Inhibition: A Review with the Focus on Poorly Soluble Drugs.

An oral route for drug administration is a more suitable route because of its ease of administration, pain avoidance, patient compliance, accommodation of various types of drug molecules, etc. But there are many factors affecting the oral absorption of the drugs. The main factor associated with oral absorption is drug solubility. Many new chemical molecules are poorly soluble in nature and can be included in BCS classes II and IV. For the administration of these drugs through the oral route, it was found that solubility is the rate limiting step. The low solubility of these drugs tends to cause precipitation in the gastrointestinaltract (GIT), affecting their bioavailability. Drug precipitation may be triggered by many factors such as insolubility of the drug in co-solvent, drug-excipient interactions, physiochemical properties of the drug, sudden change in the pH of the environment, incompatibility with the surfactant, etc. Precipitation of a drug may occur in two stages, formation of nucleation and crystal growth. To overcome precipitation, there are many strategies such as the use of polymers, the addition of surfactants, modulating drug loading and solubilizing capacity, change in the pH of the environment, etc. In this review, the causes of precipitation and diverse strategies of precipitation inhibition are critically reviewed.

Formulation and Characterization of Oral Dispersible Tablet of Aprepitant

The oral route of drug administration is more common and convenient where tablets and capsules emerged as popular dosage form but many patients have dysphasia or difficulty in swallowing which is currently affecting 35% general population. Aprepitant is anti-emetic drug and used in the treatment of chemotherapy in cancer. Fast onset of action is required in this indication there for it was thought to prepare Oral Dispersible Tablet of Aprepitant which would help to avoid first pass metabolism and improve bioavailability also Aprepitant is insoluble in water so, to increase the solubility solid dispersion method (kneading method) was used. Here, Aprepitant ODT is prepared by direct compression method using Polyplasdone XL10 as superdisitegrant and optimized by 32 Full factorial design. Here, Polyplasdone XL10 (x1) and Mannitol(x2) is use as independent variable. while dependent variable are disintegration time and wetting time. Optimized formulation F8 batch showed drug content (98.41±0.91); disintegration time is (18.02±1.20) Wetting time (22.53±0.43). The formulation is stable at 40ºc/75% RH for 30days.

Abrocitinib: A panacea for atopic dermatitis

Atopic Dermatitis [AD] is a chronic relapsing inflammatory dermatological disease characterized by itch, dry skin, localized or disseminated eczematous lesions and hyperpigmentation of skin. There are several exogeneous and endogenous risk factors for development of AD. The endogenous factors include genetic factors, atopy, skin hyperreactivity and exogeneous factors such as food, dust, pollen, epidermal, fungal, bacterial, and vaccine-associated factors. The management of AD includes topical treatments such as topical corticosteroids, topical capsaicin, topical calcineurin inhibitors and phosphodiesterase inhibitors. Systemic therapies such as corticosteroids, immunosuppressants, biologicals, gabapentinoids and antidepressants are provided to patients with inadequate systemic therapies have wide range of side effects limiting their use in many patients. Therefore, there is a need for innovative treatment options. This led to development of Janus kinase inhibitors. First generation JAK inhibitors includes Tofacitinib, Baricitinib, Ruxolitinib, Oclacitinib. Second generation drugs such as Upadacitinib and Abrocitinib are more specific towards the JAK isoforms. This review addresses the importance of Abrocitinb for the treatment of Atopic Dermatitis. Abrocitinib an oral once daily treatment for moderate to severe atopic dermatitis developed by Pfizer. Studies shows that Abrocitinib is better alternative in non- responders to Dupilumab therapy or patients with contraindications to the Dupilumab. The patient’s adherence to medication will also be better with oral route rather than injections. Abrocitinib will be widely accepted because of its clinical benefits such as reduction in itching and more convenient oral route of administration.

Impact of polyphenols on heart failure and cardiac hypertrophy: clinical effects and molecular mechanisms.

Polyphenols are abundant in regular diets and possess antioxidant, anti-inflammatory, anti-cancer, neuroprotective, and cardioprotective effects. Regarding the inadequacy of the current treatments in preventing cardiac remodeling following cardiovascular diseases, attention has been focused on improving cardiac function with potential alternatives such as polyphenols. The following online databases were searched for relevant orginial published from 2000 to 2023: EMBASE, MEDLINE, and Web of Science databases. The search strategy aimed to assess the effects of polyphenols on heart failure and keywords were "heart failure" and "polyphenols" and "cardiac hypertrophy" and "molecular mechanisms". Our results indicated polyphenols are repeatedly indicated to regulate various heart failure-related vital molecules and signaling pathways, such as inactivating fibrotic and hypertrophic factors, preventing mitochondrial dysfunction and free radical production, the underlying causes of apoptosis, and also improving lipid profile and cellular metabolism. In the current study, we aimed to review the most recent literature and investigations on the underlying mechanism of actions of different polyphenols subclasses in cardiac hypertrophy and heart failure to provide deep insight into novel mechanistic treatments and direct future studies in this context. Moreover, due to polyphenols' low bioavailability from conventional oral and intravenous administration routes, in this study, we have also investigated the currently accessible nano-drug delivery methods to optimize the treatment outcomes by providing sufficient drug delivery, targeted therapy, and less off-target effects, as desired by precision medicine standards.

Efficacy and feasibility of Apatinib and S-1 as a novel oral induction therapy in locally advanced head and neck squamous cell carcinoma: an exploratory phase 2 open-label, single-arm trial.

The current standard nonsurgical treatment for locally advanced head and neck squamous cell cancer (LA-HNSCC) is concomitant chemoradiotherapy (CRT). Neoadjuvant chemotherapy combined with CRT has been explored in HNSCC patients and is an acceptable strategy. However, the occurrence of adverse events (AEs) restricts its application. We conducted a clinical study to explore the efficacy and feasibility of a novel induction therapy with orally administered apatinib and S-1 in LA-HNSCC. This nonrandomized, single-arm, prospective clinical trial included patients with LA-HNSCCs. The eligibility criteria included histologically or cytologically confirmed HNSCC, with at least one radiographically measurable lesion detected by magnetic resonance imaging (MRI) or computerized tomography (CT) scan, age 18-75 years, and a diagnosis of stage III to IVb according to the 7th edition of the American Joint Committee of Cancer (AJCC). Patients received induction therapy with apatinib and S-1 for three cycles (3 weeks/cycle). The primary endpoint of this study was the objective response rate (ORR) to induction therapy. The secondary endpoints included progression-free survival (PFS), overall survival (OS), and AEs during induction treatment. From October 2017 to September 2020, 49 patients with LA-HNSCC were screened consecutively and 38 were enrolled. The median age of the patients was 60 years (range, 39-75). Thirty-three patients (86.8%) had stage IV disease according to the AJCC staging system. The ORR after induction therapy was 97.4% (95% confidence interval [CI]: 86.2%-99.9%). the 3-year OS rate was 64.2% (95% CI: 46.0%-78.2%) and 3-year PFS was 57.1% (95% CI: 40.8%-73.6%). The most common AEs during induction therapy were hypertension and hand-foot syndrome, which were manageable. Apatinib combined with S-1 as novel induction therapy for LA-HNSCC patients resulted in a higher-than-anticipated ORR and manageable adverse effects. With the associated safety profile and preferable oral administration route, apatinib combined with S-1 is an attractive exploratory induction regimen in outpatient settings. However, this regimen failed to show a survival benefit. https://clinicaltrials.gov/show/NCT03267121, identifier NCT03267121.

A pharmacological overview of aprepitant for the prevention of postoperative nausea and vomiting

ABSTRACT Introduction Post-operative nausea and vomiting (PONV) affects 30% of all patients undergoing surgery and up to 80% of high-risk patients. Antiemetics for PONV prophylaxis target a variety of receptor systems, with varying degrees of efficacy and side effect profile. Neurokinin −1 receptor antagonists are the most recent class of compounds investigated for PONV prophylaxis, with aprepitant being the only one currently approved for this indication. Areas covered This review covers the pathophysiology of PONV, current recommendations for PONV prophylaxis, pharmacokinetics, and pharmacodynamics of aprepitant, and the evidence for its efficacy in the management of PONV as a single agent and in combination therapy. Expert opinion Aprepitant is effective for PONV prophylaxis. It has superior antivomiting efficacy, long half-life, and favorable side effect profile. Data on antiemetic combinations involving aprepitant are limited, and it is not clear if the addition of other antiemetics to aprepitant results in improved PONV prophylaxis. The oral route of administration of aprepitant is a potential limitation in a busy clinical practice. However, the recent approval of an intravenous formulation could provide a more convenient route of administration. Aprepitant remains more expensive than other antiemetics, and there are no studies assessing the cost effectiveness of its use.

The Importance of Patient-Focused Drug Development in Pemphigus and Pemphigoid

The Importance of Patient-Focused Drug Development in Pemphigus and Pemphigoid

β-Secretase-1: In Silico Drug Reposition for Alzheimer's Disease.

The β-secretase-1 enzyme (BACE-1) performs a key role in the production of beta-Amyloid protein (Aβ), which is associated with the development of Alzheimer's disease (AD). The inhibition of BACE-1 has been an important pharmacological strategy in the treatment of this neurodegenerative disease. This study aims to identify new potential candidates for the treatment of Alzheimer's with the help of in silico studies, such as molecular docking and ADME prediction, from a broad list of candidates provided by the DrugBank database. From this analysis, 1145 drugs capable of interacting with the enzyme with a higher coupling energy than Verubecestat were obtained, subsequently only 83 presented higher coupling energy than EJ7. Applying the oral route of administration as inclusion criteria, only 41 candidates met this requirement; however, 6 of them are associated with diagnostic tests and not treatment, so 33 candidates were obtained. Finally, five candidates were identified as possible BACE-1 inhibitors drugs: Fluphenazine, Naratriptan, Bazedoxifene, Frovatriptan, and Raloxifene. These candidates exhibit pharmacophore-specific features, including the indole or thioindole group, and interactions with key amino acids in BACE-1. Overall, this study provides insights into the potential use of in silico methods for drug repurposing and identification of new candidates for the treatment of Alzheimer's disease, especially those targeting BACE-1.

Transdermal delivery of doxorubicin and methotrexate from polyelectrolyte three layer nanoparticle of graphene oxide/polyethyleneimine/dextran sulphate for chemotherapy: In vitro and in vivo studies

In the present work, novel dual drug loaded - anionic graphene oxide/cationic polyethyleneimine/poly anionic dextran sulfate (GO/PEI/DS) was synthesized by a layer-by-layer self-assembly technique for transdermal anti-cancer drug delivery. Doxorubicin (DOX) was loaded onto folic acid conjugated graphene oxide (GO) and methotrexate (MTX) was loaded onto dextran sulfate (DS). The drug carrier was characterized by fourier transform infrared spectroscopy, x-ray diffraction spectroscopy, dynamic light scattering analysis, scanning electron microscopy, atomic force microscopy, transmission electron microscopy, zeta-potential analysis, drug loading and encapsulation efficiency, equilibrium swelling studies, in vitro drug release studies, hemocompatibility assays, in vitro cytotoxicity assay, skin irritation studies, ex vivo skin permeation studies and in vivo pharmacokinetic studies.The cytotoxicity of synthesized materials was evaluated against MCF-7 breast cancer cells using an MTT assay and apoptosis assay. The synergistic effect of DOX and MTX to inhibit the growth of cancer cells was also confirmed. The final dual drug-loaded carrier showed a cell viability of 36.38 % towards MCF-7 cancer cells while it showed a cell viability of >87.65 % towards normal L929 cell lines. The in vivo pharmacokinetic studies in Wistar rats through oral and transdermal routes of administration, the transdermal route of administration of dual drug-loaded material provided a sustained and prolonged drug existence in the blood circulation system. The mean residence time of drugs in the bloodstream via oral administration was 83.98 ± 3.71 h, while that of the transdermal route of administration was 149.62 ± 6.11 h. The results revealed that the synthesized dual drug-loaded material showed a good pH-dependent controlled and sustained release profile for both DOX and MTX via the transdermal route of administration in comparison with oral delivery.

Efficacy of oral Tranexamic Acid in reducing blood loss during primary total hip arthroplasty: A comparative study

Background: Perioperative blood loss is a major concern for patients undergoing total hip arthroplasty. Intravenous Tranexamic acid is commonly used to reduce blood loss and need for blood transfusion following total hip replacement. Recent studies have shown the efficacy of oral tranexamic acid in reducing perioperative blood loss in total hip replacement.
 Method: A total of 69 patients undergoing primary total hip replacement in National Orthopaedic Hospital, Igbobi, Lagos, were recruited. Patients were randomized to receive 2gram oral tranexamic acid 2hours before incision or 1-gram intravenous tranexamic acid 10minutes before incision. Primary outcome measure was reduction in haemoglobin concentration.
 Results: There was no significant difference in mean reduction in haemoglobin concentration in the oral tranexamic acid group compared to intravenous tranexamic acid group (3.78g/dl ±1.27 and 3.61g/dl ±0.54 respectively, P- 0.49). There was no significant difference between total blood loss and requirement for blood transfusion in the two groups.
 Conclusion: Oral and intravenous routes of tranexamic acid administration have comparable efficacy in reducing blood loss and requirement for blood transfusion. Oral tranexamic acid is cheaper, easier to administer and should be considered as a safe and effective alternative to intravenous tranexamic acid.