Self-assembling Organogels Loaded with Tenoxicam for Local Intensive Pain and Inflammation Cure: In Vitro and In Vivo Correlation.

Due to tenoxicam (TX)'s poor aqueous solubility (0.072 mg/ml), it is poorly absorbable in the GIT, and the long-term oral administration of TX may cause severe GIT disturbances. Topical administration of TX can help in bypassing the GIT adverse effects. Therefore, in the present work, we constructed different pluronic/lecithin organogels (PLOs) for topical delivery of TX. PLO was constructed simply via direct mixing of an aqueous pluronic solution with lecithin solution. The prepared PLO formulations were characterized for their physicochemical properties including pH, drug content, visual inspection, viscosity, and spreadability. Also, the in vitro release and kinetic studies were carried out to investigate the mechanism of drug release. Moreover, the in vivo studies were carried out by investigating the anti-inflammatory and analgesic activities using albino male rats. The results showed that the modified PLOs have good physicochemical properties. The viscosity of the modified gels is a direct proportionality with both lecithin and pluronic concentrations. Also, subsequently, the drug release rate is directly proportional to gel viscosity. Moreover, the in vivo studies showed that the modified PLOs (F19) showed a significant ( < 0.05%) paw edema inhibition and pain analgesia compared with other investigated groups. Also, the results indicated that the increase in dose is accompanied by higher activity and a longer duration of action which extended to 12 h. Hence, the modified PLOs are promising safe candidates or vehicles for effective TX loading with sustained delivery behavior.

Enhancing early functional independence following cardiac surgery: a quality improvement programme.

Early mobility and activity programmes following cardiac surgery are vital for improved patient outcomes, as they accelerate the recovery of functional capacity and walking distance. We observed that only 5.3% of our patients achieved a Functional Independence Measurement (FIM) score of 80% or more by the third postoperative day (POD). Additionally, the average 6-minute walk distance achieved by the fourth POD was only 188 m. Therefore, a quality improvement (QI) project was implemented with the aim of attaining a FIM score of 80% by the third POD for more than 80% of patient underwent/undergoing cardiac surgery without complications.A model-for-improvement framework was used to drive continuous improvement. This project was implemented in February 2021. Baseline data were prospectively collected between November 2020 and January 2021 (preintervention). Outcomes were analysed using standard control chart rules to detect changes over time. Unpaired Student t-tests assessed significant differences in mean levels between two groups, (preintervention vs postintervention).χ2 tests were conducted between the two groups according to gender and patient satisfaction scores.The percentage of patients who achieved a FIM score of 80% or more by the third POD gradually increased to 91.4% 5 months following programme implementation and was sustained thereafter. The mean patient FIM score significantly improved to 81.20±3.77 (p<0.001) by the third POD. Similarly, the mean 6-minute walk distance increased to 267.90±36.10 m (p<0.001) by the fourth POD. The percentage of patients who displayed the level of confidence needed to carry out activities of daily living (ADL) and exercises independently at home increased to 89.4% (p<0.001) by the fifth POD. No adverse events associated with the mobility and activity programme were reported.This QI project demonstrated a substantial improvement in patient functional independence, walking distance and the level of confidence needed to independently carry out ADL and exercises following cardiac surgery.

Investigation of anti-PEG antibody response to PEG-containing cosmetic products in mice.

Polyethylene glycol (PEG), a polyether compound, is available in molecular weights from ∼300 g/mol to ∼10,000,000 g/mol. In the molecular weight range of ∼750 to ∼5000, PEG is commonly used in bioconjugation technology and nano-formulations to improve the circulation half-life of the formulations and increase their stability. In cosmetics, lower molecular weight PEG compounds such as PEG 60 or PEG 100 are widely used as emulsifiers and skin penetration enhancers. PEG polymers are generally recognized as biologically inert and non-immunogenic. However, it is recently reported that the "pre-existing" anti-PEG antibodies have been detected in high percentages of healthy individuals who have never received treatment with parenteral PEGylated formulations. To the best of our knowledge, we are the first to attempt to find an explanation for the source of pre-existing anti-PEG antibodies in healthy individuals. In a murine study, we demonstrated that topically applied PEG derivatives, present in two commercially available cosmetic products, could efficiently penetrate the stratum corneum and reach the systemic circulation. The skin penetration of PEG derivatives was further enhanced in injured or otherwise compromised skin. Daily application of cosmetic PEG derivatives primed the immune system, inducing anti-PEG IgM production. Anti-PEG IgM was detected by Day 14 in mice with normal skin, while anti-PEG IgM was detected as early as day 7 in mice with compromised skin. In addition, in mice with pre-induced circulating levels of anti-PEG IgM, topically applied PEG derivatives from cosmetic products appeared to bind to the pre-induced anti-PEG IgM, lowering blood levels. Current results indicate that PEG derivatives in cosmetic products may be an important contributor to the source of the "pre-existing" anti-PEG antibodies that have been detected in healthy individuals.

A Novel Approach for the Availability and Ocular Delivery of Tenoxicam Potassium: Synthesis, Characterization, and In Vivo Application.

Tenoxicam (TX) is a non-steroidal anti-inflammatory agent that can be used to control pain in various ophthalmic lesions like cataracts, refractive surgery, and corneal abrasion. TX has a very slightly aqueous solubility of 0.072 mg/mL resulting in difficulty to be formulated in ophthalmic solutions. This study aims to improve TX solubility by converting it into its potassium salt to achieve a target of 10 mg/mL (1%w/v) concentration of TX in the desired aqueous medium for the formulation of aqueous ophthalmic solutions. The synthesized TX salt was characterized by different evaluation parameters such as solubility studies, 1H NMR, IR, and elemental analyses. Different TX potassium solutions were formulated at concentrations of 0.5% and 1% w/v using different viscosity-imparting agents. The prepared solutions were characterized for their physicochemical properties including visual inspection, pH, rheological, in vitro release, and kinetic behavior. Also, the formulations were biologically evaluated in vivo using male albino rabbits. The obtained results showed the successful synthesis of TX salt, as indicated by IR and NMR, and elemental analysis. The solubility study showed that the solubility of TX was improved hugely to 18 mg/mL (250-fold). In addition, the results showed that the prepared formulations showed acceptable physicochemical properties. The highest release rate was obtained with formula F1, which contains no viscosity-imparting agents. While as, the lowest release rate was obtained in the case of formula F9, composed of Pluronic F127 (12% w/v). The in vivo results showed that TX optimized ophthalmic solutions F8 and F9 inhibited the redness and edema in an extended or sustained manner.

Clinical study on the efficacy of hepatitis B vaccination in hepatitis C virus related chronic liver diseases in Egypt.

BACKGROUND: Chronic hepatitis B (HBV) and C virus (HCV) infections represent significant public health issues internationally. HBV vaccination has high sero-conversion rates in patients with mild to moderate chronic liver disease but has reduced efficacy in advanced stages. AIM: to evaluate the efficacy of hepatitis B vaccination in HCV-related chronic liver disease and identify possible factors that may contribute to hypo-responsiveness in those patients. METHODS: Our study was a retrospective observational clinical study carried out at the tropical medicine department. It was conducted on 500 individuals (400 chronic HCV patients and 100 healthy controls). Individuals were divided into 5 groups: A (control group), B (cirrhotic patient not receiving treatment), C (chronic hepatitis patients receiving treatment), D (cirrhotic patients receiving treatment), and E (HCC patients receiving treatment). All individuals were subjected for comprehensive history taking, clinical examination, laboratory investigations, and assessment of anti-HBs titer. RESULTS: There is an inverse relationship between the level of anti-HBs Abs and the duration of vaccine. Diabetes and presence of cirrhosis have statistically significant relationship with serum anti-HBs Abs titer (P = 0.007). Oral DAAs therapy is associated with reduced response to HBV vaccine (only 31.75% of the patients were protected). CONCLUSION: HCV infection and its complications significantly impair HBV vaccine response. Levels of anti-HBs Abs decline progressively with increasing duration from the last dose in immunization schedule of HBV vaccine. Diabetes and presence of cirrhosis being the main risk factors for vaccine hypo-responsiveness, also oral DAAs therapy is associated with reduced response to HBV vaccine.

Brain Targeting of Citicoline Sodium via Hyaluronic Acid-Decorated Novel Nano-Transbilosomes for Mitigation of Alzheimer's Disease in a Rat Model: Formulation, Optimization, in vitro and in vivo Assessment.

Background: Alzheimer's disease (AD) is one of the furthermost advanced neurodegenerative disorders resulting in cognitive and behavioral impairment. Citicoline sodium (CIT) boosts the brain's secretion of acetylcholine, which aids in membrane regeneration and repair. However, it suffers from poor blood-brain barrier (BBB) permeation, which results in lower levels of CIT in the brain. Purpose: This study targeted to encapsulate CIT into novel nano-platform transbilosomes decorated with hyaluronic acid CIT-HA*TBLs to achieve enhanced drug delivery from the nose to the brain. Methods: A method of thin-film hydration was utilized to prepare different formulae of CIT-TBLs using the Box-Behnken design. The optimized formula was then hyuloranated via integration of HA to form the CIT-HA*TBLs formula. Furthermore, AD induction was performed by aluminum chloride (Alcl3), animals were allocated, and brain hippocampus tissue was isolated for ELISA and qRT-PCR analysis of malondialdehyde (MDA), nuclear factor kappa B (NF-kB), and microRNA-137 (miR-137) coupled with immunohistochemical amyloid-beta (Aß1-42) expression and histopathological finding. Results: The hyuloranated CIT-HA*TBLs formula, which contained the following ingredients: PL (300 mg), Sp 60 (43.97 mg), and SDC (20 mg). They produced spherical droplets at the nanoscale (178.94 ±12.4 nm), had a high entrapment efficiency with 74.92± 5.54%, had a sustained release profile of CIT with 81.27 ±3.8% release, and had ex vivo permeation of CIT with 512.43±19.58 µg/cm2. In vivo tests showed that CIT-HA*TBL thermogel dramatically reduces the hippocampus expression of miR-137 and (Aß1-42) expression, boosting cholinergic neurotransmission and decreasing MDA and NF-kB production. Furthermore, CIT-HA*TBLs thermogel mitigate histopathological damage in compared to the other groups. Conclusion: Succinctly, the innovative loading of CIT-HA*TBLs thermogel is a prospectively invaluable intranasal drug delivery system that can raise the efficacy of CIT in Alzheimer's management.

Polyethylene glycol (PEG): The nature, immunogenicity, and role in the hypersensitivity of PEGylated products.

Polyethylene glycol (PEG) is a versatile polymer that is widely used as an additive in foods and cosmetics, and as a carrier in PEGylated therapeutics. Even though PEG is thought to be less immunogenic, or perhaps even non-immunogenic, with a variety of physicochemical properties, there is mounting evidence that PEG causes immunogenic responses when conjugated with other materials such as proteins and nanocarriers. Under these conditions, PEG with other materials can result in the production of anti-PEG antibodies after administration. The antibodies that are induced seem to have a deleterious impact on the therapeutic efficacy of subsequently administered PEGylated formulations. In addition, hypersensitivity to PEGylated formulations could be a significant barrier to the utility of PEGylated products. Several reports have linked the presence of anti-PEG antibodies to incidences of complement activation-related pseudoallergy (CARPA) following the administration of PEGylated formulations. The use of COVID-19 mRNA vaccines, which are composed mainly of PEGylated lipid nanoparticles (LNPs), has recently gained wide acceptance, although many cases of post-vaccination hypersensitivity have been documented. Therefore, our review focuses not only on the importance of PEGs and its great role in improving the therapeutic efficacy of various medications, but also on the hypersensitivity reactions attributed to the use of PEGylated products that include PEG-based mRNA COVID-19 vaccines.

Tolmetin Sodium Fast Dissolving Tablets for Rheumatoid Arthritis Treatment: Preparation and Optimization Using Box-Behnken Design and Response Surface Methodology.

Tolmetin sodium (TLM) is a non-steroidal anti-inflammatory drug (NSAIDs). TLM is used to treat inflammation, skeletal muscle injuries, and discomfort associated with bone disorders. Because of the delayed absorption from the gastro intestinal tract (GIT), the currently available TLM dosage forms have a rather protracted start to the effect, according to pharmacokinetic studies. The aim of this study was to create a combination for TLM fast dissolving tablets (TLM-FDT) that would boost the drug's bioavailability by increasing pre-gastric absorption. The TLM-FDTs were developed using a Box-Behnken experimental design with varied doses of crospovidone (CP), croscarmellose sodium (CCS) as super-disintegrants, and camphor as a sublimating agent. In addition, the current study used response surface approach to explore the influence of various formulation and process factors on tablet qualities in order to verify an optimized TLM-FDTs formulation. The optimized TLM-FDTs formula was subsequently evaluated for its in vivo anti-inflammatory activity. TLM-FDTs have good friability, disintegration time, drug release, and wetting time, as well as fast disintegration and dissolution behavior. Significant increase in drug bioavailability and reliable anti-inflammatory efficacy were also observed, as evidenced by considerable reductions in paw thickness in rats following carrageenan-induced rat paw edema. For optimizing and analyzing the effect of super-disintegrants and sublimating agents in the TLM-FDTs formula, the three-factor, three-level full factorial design is a suitable tool. TLM-FDTs are a possible drug delivery system for enhancing TLM bioavailability and could be used to treat rheumatoid arthritis.

A mouse model for studying the effect of blood anti-PEG IgMs levels on the in vivo fate of PEGylated liposomes.

The presence of anti-polyethylene glycol (PEG) antibodies in the systemic circulation might have potential implications for the therapeutic activity of PEGylated products in vivo in the clinic. In order to study the effect of pre-existing anti-PEG antibodies on the in vivo fate and the therapeutic efficiency of PEGylated therapeutics, we developed a BALB/c mouse model by virtue of the intraperitoneal (i.p.) inoculation of hybridoma cells (HIK-M09 and HIK-M11), secreting monoclonal anti-PEG IgM, mimicking the presence of pre-existing anti-PEG antibodies in the blood. In the model, the titers of anti-PEG IgM in the blood increased as a function of hybridoma cells numbers and time after i.p. inoculation. The in vivo levels of anti-PEG IgM decreased in a dose-dependent manner, following i.v. administration of empty PEGylated liposomes. C26 tumor-bearing mice with measurable levels of anti-PEG IgM, receiving i.v. injection of DiR-labeled empty PEGylated liposomes, showed lower levels of liposomal tumor accumulation and higher levels of liver and spleen accumulation, compared to C26 tumor-bearing mice without measurable anti-PEG IgM. This specifies that the presence of anti-PEG IgM in the murine circulation induced accelerated blood clearance of PEGylated liposomes and reduced their tumor accumulation. The biodistribution and antitumor efficacy of commercially available doxorubicin (DXR)-containing PEGylated liposomes, Doxil®, were scrutinized in the anti-PEG IgM mouse model. In C26 tumor-bearing mice having circulating anti-PEG IgM, at 24 h after injection almost no DXR was observed in blood and tumor, and increased DXR accumulation was observed in spleen and liver, compared to tumor-bearing mice with no circulating anti-PEG IgM. The antitumor efficacy of Doxil® was significantly compromised in the C26 tumor-bearing mice in the presence of anti-PEG IgM. These results demonstrate that the anti-PEG IgM mouse model could be a useful prognostic indicator for the therapeutic effectiveness of different formulations of PEGylated therapeutics in pre-clinical studies.

Using Bio-Layer Interferometry to Evaluate Anti-PEG Antibody-Mediated Complement Activation.

The purpose of this study was to develop a Bio-layer interferometry (BLI) system that could be an alternative approach for the direct evaluation of anti-polyethylene glycol (PEG) immunoglobulin M (IgM)-mediated complement activation of the accelerated blood clearance (ABC) phenomenon. Complement activation is well known to play an important role in the clearance of PEGylated and non-PEGylated nanomedicines following intravenous injection. This complement system is also thought to be responsible for the ABC phenomenon wherein repeated injections of PEGylated products are bound by anti-PEG antibodies. This study used three different sources of anti-PEG antibodies: HIK-M09 monoclonal antibodies (mAbs); HIK-M11 mAbs; and antiserum containing polyclonal anti-PEG IgMs. 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-n-[methoxy (polyethylene glycol)-2000] (mPEG2000-DSPE) was immobilized as an antigen on aminopropyl silane biosensor chips of BLI. All anti-PEG IgMs in the sources increased the signals (thickness of the layer around the sensor tip) regarding binding of anti-PEG antibodies to PEG on the chips. In all anti-PEG IgM sources, further increases in the signals were observed when incubated in naïve mouse serum, which is a complement source, but not in heat inactivated (56 °C, 30 min) mouse serum, which abolishes complement activity. These findings show that the complement activation mediated via anti-PEG IgMs, which occurred on the sensor chips, was detected via BLI analysis. The complement activation induced by all anti-PEG IgM sources was confirmed via conventional enzyme-linked immunosorbent assay (ELISA), which is the conventional mode for detection of complement activation. Our study results show that BLI is a simple alternative method for the detection of complement activation.

Robotic Coronary Revascularization is Feasible and Safe: 10-year Single-Center Experience.

Objective: The purpose of this study is to investigate the outcomes of patients undergoing robotic surgical coronary revascularization whether total endoscopic coronary artery bypass (TECAB) or robotic-assisted minimally invasive direct coronary artery bypass (RA-MIDCAB) in our center. Methods: This is a retrospective single-center study. It was conducted in the heart hospital at Hamad Medical Corporation, Qatar. We retrospectively studied all cases that had single grafts, left internal mammary artery (LIMA) to left anterior descending (LAD) coronary artery through a minimally invasive approach, either TECAB grafting or RA-MIDCAB grafting operations between February 2009 and December 2020. Both procedures were performed with the assistance of the da Vinci robotic system. In TECAB, the robotic system was used to harvest LIMA and perform the anastomosis with LAD. Whereas in RA-MIDCAB, LIMA was harvested by the robotic system but the anastomosis of LIMA to LAD was performed under direct vision through a small anterior thoracotomy incision. Seventy-one patients' files from the medical records department were reviewed. Preoperative data included age, gender, ethnicity, body mass index (BMI), cardiac risk factors, Euro score, presentation, and the results of the cardiac investigations. The intraoperative data were the type of procedure, operative time, and whether the procedure was completed as planned or converted to thoracotomy or sternotomy. The postoperative data included the length of hospital stay, postoperative complications, 3-month clinic follow-up, and the need for repeat coronary angiography or revascularization. Results: We found that our patients' ages ranged from 31 to 70 years. The majority were males, with 64 (90.14%) patients. Thirty-one (44.93%) patients were found to have a BMI of 25-29.9 Kg/m2. Forty-seven (66.2%) patients were hypertensive and 37 (52.11%) were diabetic. Dyslipidemia was reported in 35 (50%) patients. TECAB was the primary procedure in 47 (66.2%) patients and the rest underwent RA-MIDCAB. Only 7 (10.14%) patients underwent a planned hybrid procedure. The procedure was completed as planned in 52 (73.2%) patients. The mean operative time was 355.9 ± 95.79 min. Fourteen (19.72%) TECAB procedures were converted to MIDCAB, whereas 5 (7.04%) required sternotomy. Thirteen (18.3%) patients were extubated on the table, 47 (66%) patients were extubated in <24 h, and 7 (9.8%) patients were extubated after 24 h of the procedure. Forty-two (59%) patients stayed only 24 h in ICU and 24 (33.8%) spent more than 24 h. Blood transfusion was required in 8 (11.2%) patients. Only 2 (2.8%) patients experienced bleeding after the surgery. Postoperative infection was observed in 3 (4.29%) patients. No new cerebrovascular accident was detected among the patients after the procedure. Median postoperative hospital stay was 5 days, interquartile range 2, range (2-39). During the 3-month postoperative follow-up, we found that three unplanned coronary angiographies were required for repeat intervention, one of them for LIMA-LAD anastomosis. No redo surgery was performed. Thirty-day mortality was reported in two patients only. Conclusion: From our experience over more than 10 years in robotic cardiac surgery in Qatar, we believe that robotic coronary revascularization is safe and feasible in selected patients mainly with single vessel coronary artery disease but should be performed in specialized centers and by robotic-trained surgeons.

Mitral valve replacement through mini sternotomy after long ECMO course: Case report.

INTRODUCTION: Mitral regurgitation (MR) is defined as an abnormal reversal of blood flow from the left ventricle to the left atrium (LA). It is caused by disruption in any part of the mitral valve apparatus. Surgical intervention remains the mainstay of management for severe cases. CASE SUMMARY: We are reporting a case of pneumonia with severe sepsis, that had a complicated hospital course. The patient developed multi-organ failure. Echocardiography on admission showed severe mitral regurgitation. He required early mechanical ventilation and then Veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO) over 29 days. He might be the first case of Coronavirus Disease 2019 (COVID-19) in our hospital. Mitral valve replacement was done after stabilization of the patient and weaning from the ECMO. DISCUSSION: Our report demonstrates that the use of a long term VV-ECMO as a bridge for stabilization, facilitates management of the critically ill respiratory failure patient with severe MR and patient outcomes. Still the long-term results and the optimal timing of intervention need more research to define. CONCLUSION: Our report demonstrates that the use of a long term VV ECMO facilitates management of patients with respiratory failure associated with severe MR. Future studies focusing on stabilizing such patients, might help to define the optimal timing for intervention in these patients and the long-term outcome.

Association of ruptured sinus of Valsalva aneurysm and congenital ventricular septal defect: a case series.

BACKGROUND: Ruptured sinus of Valsalva aneurysm (RSOVA) is rare, and it is more common in Asians. Typically, the patient presents with acute/subacute shortness of breath (SOB) and chest pain. Echocardiography is the gold standard for diagnosis in most of these cases. Surgery has remained the first line of management. CASE SUMMARY: We present two cases of RSOVA in which the patients presented to the emergency department with SOB. Their preoperative echocardiography results showed RSOVA into the right ventricle. During surgical repair, ventricular septal defect (VSD) was also found. DISCUSSION: RSOVA is frequently associated with other congenital anomalies, and most often with VSD. In our cases, we believe that VSDs were missed preoperatively because either the large aneurysmal sacs covered the VSD or there was overlap between the two shunts. Additionally, in the first case, right ventricular pressure was high approaching systemic pressure, which probably reduced the shunt across the VSD. Early intervention is recommended to prevent endocarditis or enlargement of the ruptured aneurysm; long-term results were excellent after surgical repair. Most patients undergo surgery between 20 and 40 years of age, and the reported survival rate is 95% at 20 years. If left untreated, patients typically die of heart failure or endocarditis within 1 year after onset of symptoms.

Optimization and evaluation of propolis liposomes as a promising therapeutic approach for COVID-19.

The present work aimed to develop an optimized liposomal formulation for enhancing the anti-viral activity of propolis against COVID-19. Docking studies were performed for certain components of Egyptian Propolis using Avigan, Hydroxychloroquine and Remdesivir as standard antivirals against both COVID-19 3CL-protease and S1 spike protein. Response surface methodology and modified injection method were implemented to maximize the entrapment efficiency and release of the liposomal formulation. The optimized formulation parameters were as follow: LMC of 60 mM, CH% of 20% and DL of 5 mg/ml. At those values the E.E% and released % were 70.112% and 81.801%, respectively with nanosized particles (117 ± 11 nm). Docking studies revealed that Rutin and Caffeic acid phenethyl ester showed the highest affinity to both targets. Results showed a significant inhibitory effect of the optimized liposomal formula of Propolis against COVID-3CL protease (IC50 = 1.183 ± 0.06) compared with the Egyptian propolis extract (IC50 = 2.452 ± 0.11), P < 0.001. Interestingly, the inhibition of viral replication of COVID-19 determined by RT_PCR has been significantly enhanced via encapsulation of propolis extract within the liposomal formulation (P < 0.0001) and was comparable to the viral inhibitory effect of the potent antiviral (remdesivir). These findings identified the potential of propolis liposomes as a promising treatment approach against COVID-19.

Preformulation-Assisted Design and Characterization of Modified Release Gastroretentive Floating Extrudates Towards Improved Bioavailability and Minimized Side Effects of Baclofen.

Baclofen immediate release mode of administration exhibit sharp plasma peaking that results in the emergence of side effects like hypotension. This research employs preformulation studies to design an optimum dosage form for baclofen to enhance therapeutic outcomes. These studies include partition coefficient and ex-vivo permeation studies. Partition coefficient was found to be 1.27 at pH 7.4. Permeation studies confirmed the presence of specialized transport mechanism through the GIT. It was concluded that an ideal formulation of baclofen should provide slow-release of the drug to avoid sharp peaking. Modified-release floating extrudates of baclofen were prepared using Carbopol 934 and HPMC with different gas-forming agents. Different release-retarding materials (Eudragit L100, Eudragit RS100 and Cetyl alcohol) were used as ingredients in the binder solutions. The prepared extrudates were assessed for their drug content, floating ability, friability properties and in vitro release properties. The prepared extrudates recorded buoyance characteristics for 24 h with a floating lag time varying from 0 to 73.34 s. The optimized extrudates manifested extended baclofen release for up to 8 h compared to 0.2 h for marketed baclofen tablets. This approach was found efficient to provide greater bioavailability and minimize hypotension associated with commercial baclofen tablets.

Ruptured Sinus Of Valsalva Into The Right Ventricle A New Management Strategy.

We present 2 cases presented to the emergency department with shortness of breath (SOB). Their preoperative echocardiographies showed ruptured right sinus of Valsalva (RSOV) into the right ventricle (RV). Ventricular septal defect (VSD) was diagnosed only intraoperatively.

Effects of Levetiracetam Compared to Valproate on Cognitive Functions of Patients with Epilepsy.

OBJECTIVE: This study compared the effect of levetiracetam (LEV) as monotherapy to sodium valproate (VPA) as monotherapy on cognitive functions in patients with epilepsy. METHODS: This was a comparative prospective study on 50 patients with newly diagnosed epilepsy started on antiseizure medications. Patients were selected from the neurology-outpatient clinics at Minia University Hospital, Minia, Egypt. They were divided into two groups: group treated with LEV and group treated with VPA. All patients were subjected to cognitive function assessment using reaction-time tests, trail-making tests, and Wisconsin card-sorting test before treatment and 3 months after treatment. RESULTS: Both groups of patients showed reduction in seizure frequency. However, patients on LEV showed significant improvement in measured cognitive functions 3 months after starting treatment, while patients in the VPA group showed significant impairment in measured cognitive functions 3 months after starting treatment. CONCLUSION: Both groups of patients showed reduction in seizure frequency. However, patients on LEV showed significant improvement in measured cognitive functions 3 months after starting treatment, while patients in the VPA group showed significant impairment in measured cognitive functions 3 months after starting treatment.

Silymarin loaded floating polymer(s) microspheres: characterization, in-vitro/in-vivo evaluation.

Silymarin has a short half-life (4-6 hours) which leads to necessity of frequent administration. Besides, it suffers from intestinal degradation. Thus, our study aims to formulate encapsulated floating microspheres using different polymers as HPMC, EC and a blend of them. Emulsion solvent evaporation technique was applied for preparation of microspheres. Parameters considered during preparation are drug: polymer ratio and emulsifier concentration. Selected formulations were characterized by SEM and subjected for assessment by drug entrapment efficiency, buoyancy for 12 hr, in- vitro drug release, kinetics of release and stability. In-vivo bio-equivalence study was performed using albino rabbits. Formula F24 (treatment II) exhibited high % buoyancy (73.4), higher t90 (190.7 day), high Cmax (1021.3 ng/ml) and Tmax (6 h) with a significant difference between it and treatment I (Silymarin plus) after carrying out ANOVA study. Also formula F24 exhibited MRT (hr) equal 9.44 ± 0.03 and high relative bioavailability RB% (227%), which indicates promising microspheres that could be used for effective management of liver disease.

Applying Different Techniques to Improve the Bioavailability of Candesartan Cilexetil Antihypertensive Drug.

PURPOSE: The objective of this study was to compare different techniques to enhance the solubility and dissolution rate, and hence the bioavailability of candesartan cilexetil. METHODS: To achieve this target, various techniques were employed such as solid dispersions, inclusion complexes, and preparation of candesartan nanoparticles. Following the preparations, all samples were characterized for their physicochemical properties, and the samples of the best results were subjected to further bioavailability studies. RESULTS: Results of dissolution studies revealed an increase in the dissolution rate of all samples. The highest dissolution rate was achieved using solid dispersion of the drug with PVP K-90 (1:4). Physicochemical investigations (XR, DSC, and FT-IR) suggested formation of hydrogen bonding and changing in the crystalline structure of the drug. Regarding the inclusion complexes, more stable complex was formed between HP-ß-CD and CC compared to ß-CD, as indicated by phase solubility diagrams. Antisolvent method resulted in the preparation of stable nanoparticles, as indicated by ζ potential, with average particle size of 238.9 ± 19.25 nm using PVP K-90 as a hydrophilic polymer. The best sample that gave the highest dissolution rate (CC/PVP K-90 1:4) was allowed for further pharmacokinetic studies using UPLC MS/MS assay of rabbit plasma. Results showed a significant increase in the bioavailability of CC from ~15% to ~48%. CONCLUSION: The bioavailability of CC was significantly improved from ~15% to ~48% when formulated as SDs with PVP K-90 with 1:4 drug:polymer ratio.

Design, characterization and in vivo evaluation of modified release baclofen floating coated beads.

Baclofen is a centrally acting skeletal muscle relaxant approved by the US Food and Drug Administration (FDA) for the treatment of muscle spasticity, but the immediate release mode of administration and rapid absorption has been associated with adverse effects. The main objective of this study was to prepare modified release floating beads of baclofen in order to decrease the unwanted side effects. The beads were prepared using alginate and coated with Eudragit RS100, Eudragit L100 and cetyl alcohol. They were evaluated for their encapsulation efficiency, buoyance characteristics, morphology, and in vitro release. They have also been tested in vivo for their oral bioavailability and potential side effects. The prepared beads showed floating properties up to 12 h with different lag times ranging from 45.67 to 72.33 sec. Morphological evaluation using scanning electron microscopy (SEM) revealed that the coated beads show smooth with no pores or cracks surfaces. Real-time morphology of the beads during in vitro release testing was studied by the SEM. Optimized formulation of baclofen coated beads exhibited favorable mechanical properties, in addition, it provided extended baclofen release for up to 6 h. In addition, in vivo studies showed that the coated beads effectively decreased the hypotensive side effect associated with rapid plasma peaking from Baclofen® immediate-release tablets. In addition, there were significant differences between the values of Cmax, Tmax, and AUC0-24 of optimized modified release baclofen floating formulations when compared to Baclofen® immediate-release tablets.