Oral Suspension Research Articles

Fabrication of prostructured spanlastics gel for improving transdermal effect of dapagliflozin: In vitro characterization studies and in vivo antidiabetic activity

Dapagliflozin is a recently approved glucose-lowering agent for the management of type II diabetes mellitus. Low solubility and stability lead to its poor oral bioavailability. Prostructured spanlastic gel is very less hydrated preform of spanlastic vesicles. Therefore, the aim of this study was to explore the potential of prostructured spanlastic gel for enhancing both drug stability and transdermal delivery. The prostructured spanlastic gel formulations were fabricated by coacervation phase separation method, using Span 60 together with Tween 80 or Myrj 52 as an edge activator. Formulations were characterized for drug content, in vitro release and ex vivo skin permeability. Verification of vesicular form was assessed by hydration and the resultant formulations were characterized. Selected formulations were assessed for morphology, interaction of drug with other components, stability and antidiabetic activity. Drug content percentage of spanlastic gels was found to be in range 98.1 ± 1.9 to 94.2 ± 2.0 %. Significant (p < 0.05) increase in drug release rate was observed when edge activator concentration was greater than 30 %. Tween 80 containing formulations exhibited higher skin permeation than Myrj 52 containing ones at the same concentration of edge activator. Spanlastic vesicles were formed by hydration and had entrapment efficiency percentages ranging from 65.06 ± 0.87 % to 40.36 ± 0.95 %, mean vesicle sizes ranging from 136.1 nm to 56.52 nm and zeta potential values ranging from −29.7 mV to −6.94 mV. The morphologic examination verified formation of nanovesicular form. Thermal analysis and FT-IR confirmed encapsulation of drug inside spanlastic vesicles. Spanlastic gels showed higher stability and skin permeability when compared to vesicular form in hydroalcoholic gel. Spanlastic gels also showed prolonged hypoglycemic effect and blood glucose level reached below 135 ± 4.7 mg/dL after 24h, when compared to hydroalcoholic gel (273 ± 3 mg/dL) and oral suspension (271 ± 5 mg/dL). In conclusion, spanlastic gel could be a promising carrier for enhancing transdermal delivery of dapagliflozin, offering both sustained and enhanced antidiabetic activity.

Anti-Emetics in Children Receiving Chemotherapy for Solid Tumors and Leukemia: Pharmacology and Optimization of Therapy for Nausea and Vomiting.

The management of chemotherapy-induced nausea and vomiting (CINV) in children remains challenging due to differences in the chemotherapy regimens, their relative emetogenicity compared to that in adults and differences in drug metabolism and the available formulations. The common four classes of anti-emetics used for the treatment and prophylaxis of CINV in children include dexamethasone, neurokinin-1 receptor antagonists, 5-hydroxytryptamine-3 receptor antagonists (5HT3RAs), and olanzapine. The appropriate dose of dexamethasone for CINV prophylaxis in children is unknown, with a significant variability in dosage ranging between 6 and 32 mg/m2/day. The dose of dexamethasone is decreased by 30% when this drug is combined with (fos)aprepitant in children, in contrast to a decrease of 50% required in adults. The use of aprepitant in younger children (<12 years) is often hampered by the non-availability of oral suspension formulations in many countries; alternatively, 80 mg capsules are administered for 1-3 days in certain institutes to children weighing between 15 and 40 kg. Among the different 5HT3RAs, palonosetron is comparatively metabolized faster in children than in adults, requiring a higher dosage for similar efficacy to that achieved in adults. Olanzapine is a newer agent, used in doses between 0.1 and 0.14 mg/kg/day in children, with good anti-emetic efficacy, but has sedation and hyperglycemia as concerning adverse effects. Drug interactions between anti-emetics and between anti-emetics and chemotherapy/supportive agents (azole antifungals, cyclosporine, arsenic trioxide), especially QTc prolongation, should be considered during prescription.

Brain-targeted nasal chrysin microemulsion for reducing oxidative stress in Parkinson's disease: Pharmacodynamic, biochemical evaluation and brain distribution studies

Chrysin, a flavone reported to treat Parkinson's, has limited oral bioavailability due to poor solubility and extensive pre-systemic metabolism. Therefore, a chrysin microemulsion (Chy-ME) was developed to improve bioavailability and brain targeting for treating Parkinson's disease via the nasal route. Chy-ME was prepared using the phase titration method and characterized for physicochemical parameters, nasociliotoxicity, and anti-Parkinson activities in a rotenone-induced experimental rat model. Chy-ME showed spherical globules with a size of 365.03 nm ± 6.8, a PDI of 0.107 ± 0.0316 and a zeta potential of −24.86 mV ± 2.286. It was non-irritant to the nasal mucosa and had in vitro and ex vivo drug release of 90.52 % and 68.67 %, respectively at 24 h. The in vivo study showed significantly improved locomotor activity and catalepsy score in the Chy-ME treated group than in oral or nasal chrysin suspension groups in rats. Chy-ME treatment showed elevated dopamine levels than the other two groups. Also, enhanced oxidative stress markers, i.e., SOD, GSH, and catalase levels, indicated the antioxidant potential of Chy-ME linked with preventing neuronal damage in Parkinson's. The maximum chrysin amount was estimated in the Chy-ME group (8.3212 ± 1.8125 μg/mL) than in oral (4.1364 ± 1.1095 μg/mL) or nasal (5.0879 ± 0.0058 μg/mL) suspension groups in the brain distribution study. In vivo studies revealed the brain-targeting potential of Chy-ME, evidenced by a substantial alleviation of Parkinson's symptoms, increased dopamine levels, improved oxidative stress markers and higher chrysin content in the brain. Therefore, nasal delivery of chrysin could overcome poor oral bioavailability and be explored for treating Parkinson-related symptoms as a brain-targeted approach.

The study of marketing opportunities for the use of the raw material of feverfew (Tanacetum parthenium L.) in the pharmacotherapy of musculoskeletal system diseases

Aim. To form a modern idea of the market structure and trends in the consumption of drugs for the pharmacotherapy of rheumatoid arthritis, to determine the possible potential for use of plant raw material of feverfew (Tanacetum parthenium). Materials and methods. The study was conducted using the structural analysis, logical and graphical methods, and marketing analysis methods. Results. It was found that in the pre-war period the market for drugs affecting the musculoskeletal system developed quite vigorously – its growth rate in the period of 2020-2021 ranged from 16 to 29 % in natural units and from 20 to 30 % in monetary terms. According to the structure of producing countries, the market was significantly import-dependent. The market for synthetic drugs was quite saturated, represented by various dosage forms – tablets, powder for suspension, injection solutions (ampoules), granules, capsules, sachets, alcohol solutions, oil solutions, suppositories, oral suspensions, transdermal patches, gels, ointments. The research was conducted taking into account the study of marketing opportunities for the use of the raw material of Tanacetum parthenium in the pharmacotherapy of diseases of the musculoskeletal system since this raw material had certain advantages compared to synthetic analogs. It should be noted that the market of herbal medicines for the treatment of the musculoskeletal system diseases or the prevention of their manifestations is very limited and is represented by a minimum number of product items and one representative of the medicinal flora – Symphytum officinale. In addition, 90 % of the market for this group of drugs belongs to foreign manufacturers. Although research of the market for biological supplements indicates a certain demand for products based on the medicinal plant raw material. Conclusions. Based on the trends identified, we can state the positive development of the market for drugs that affect the musculoskeletal system, the prospects for the development of drugs based on the medicinal plant raw material, including Tanacetum parthenium.

Effectiveness of Bacillus genus application in the treatment of osteoarthritis by bioactive fish concentrate

Background. Understanding the impact of gut microbiota on the development of osteoarthritis (OA) and investigating the potential of probiotics as a treatment remain crucial areas of research. The study aimed to evaluate the efficacy of a Bacillus-based probiotic in combination with a bioactive marine fish concentrate for the OA treatment. Materials and methods. This study included 38 patients diagnosed with grade II knee OA. A structural-modifying drug containing 0.2 ml of bioactive concentrate derived from small marine fish, was administered every other day in a dose of 2.0 ml (10 intramuscular injections in total) for 21 days. Twenty patients (main group) additionally received a probiotic containing bacteria of the genus Bacillus (B.subtilis, B.licheniformis, B.amyloliquefaciens, B.megaterium, B.pumilus) in the dosage form of oral suspension daily for the entire treatment period of 21 days. Clinical efficacy was assessed by the Western Ontario McMaster Osteoarthritis Index (WOMAC), the questionnaire was comple­ted by all patients before the study and after 3, 7, 14 and 21 days of the therapy. Results. The findings showed a significant reduction in pain by 40.6 % (p &lt; 0.001), stiffness by 36.8 % (p &lt; 0.001), and improvement in knee function by 26.6 % (p &lt; 0.05) in the main group (undergoing combined therapy with bioactive fish concentrate and the probiotic) on the 7th day of treatment. In the comparison group, a decrease in pain by 27.4 % (p &lt; 0.05), stiffness by 25.0 % (p &lt; 0.05), and improvement in joint function by 28.9 % (p &lt; 0.05) were observed only on the 14th day of therapy. Conclusions. It was demonstrated that administering a probiotic composition containing bacteria from the genus Bacillus enhances the efficacy of bioactive sea fish concentrate in treating OA. Reduction in pain, stiffness, and improvement in joint function can be observed as early as the 7th day after initiating their combined use. In contrast, when using the bioactive concentrate of marine fish alone, the clinical effect is typically observed by the 14th day of treatment.

Relative Bioavailability of Cenobamate Administered as a Crushed Tablet, Either Orally or via Nasogastric Tube, versus an Intact Whole Tablet.

Cenobamate is approved for the treatment of focal seizures in adults and is currently available as an oral tablet. Alternative methods of drug administration are needed for patients who are unable to swallow whole intact tablets. This phase 1, open-label, randomized, single-dose, three-way crossover (3-period, 3-treatment, 6-sequence) study (NCT05572255), conducted in healthy volunteers, assessed the relative bioavailability of a crushed 200-mg cenobamate tablet administered orally or via nasogastric (NG) tube compared with an intact 200-mg tablet. Each treatment was separated by a 13-day washout period. Plasma samples for cenobamate concentration analysis were collected pre-dose and at multiple time points up to 264 h post-dose. Standard bioequivalence study criteria were applied to the relative bioavailability assessments. All 90% confidence intervals of test-to-reference geometric mean ratios for cenobamate pharmacokinetic parameters (Cmax, AUClast, and AUCinf) were within 85-110% (predefined limit, 80-125%), suggesting no difference in cenobamate exposures following administration of an intact tablet orally or a crushed tablet orally or via NG tube. All treatment-emergent adverse events (TEAEs) were classified as mild and resolved. There were no deaths or other serious AEs (SAEs), and no TEAEs led to discontinuation. Our results indicate that the administration of cenobamate as a crushed tablet taken orally or via an NG tube can provide additional flexibility when patients cannot swallow intact tablets. Based on the results of this study, cenobamate is now approved by FDA to be taken whole or the tablets can be crushed. The crushed tablet can be mixed with water and either administered by mouth as an oral suspension or administered via a nasogastric tube.

Evaluation of Posaconazole Serum Concentrations Achieved With Delayed-release Tablets and Oral Suspension in Patients Undergoing Intensive Chemotherapy for Acute Myeloid Leukemia and Myelodysplastic Syndrome.

Data on posaconazole serum levels of patients on prophylaxis with delayed-release tablets or oral suspension during intensive chemotherapy for acute myeloid leukemia and myelodysplastic syndrome are scarce. In this analysis, the proportion of patients with acute myeloid leukemia/myelodysplastic syndrome achieving posaconazole target concentrations with delayed-release tablets was higher than with oral suspension.

Mucoadhesive Budesonide Solution for the Treatment of Pediatric Eosinophilic Esophagitis.

Eosinophilic Esophagitis is an antigen-mediated inflammatory disease characterized by thickening of the esophageal wall, leading to dysphagia, vomiting, reflux, and abdominal pain. This disease can be treated with a therapeutic approach ranging from diet to pharmacological therapy. Jorveza® (budesonide) and Dupixent® (dupilumab) are treatments for Eosinophilic Esophagitis approved by the European Medicines Agency in adults but not in children. Budesonide-based extemporaneous oral liquid suspensions could be prepared for pediatric use. The main limit of this formulation is that budesonide needs a longer residence time on the esophageal mucosa to solubilize and diffuse in it to exert its local anti-inflammatory effect. Herein, we propose the development of an extemporaneous mucoadhesive oral budesonide solution for the pediatric population. A liquid vehicle containing hydroxypropyl-beta-cyclodextrin as a complexing agent and carboxymethylcellulose sodium as a mucoadhesive excipient was used to prepare budesonide-based formulations. A stable solution at a concentration of 0.7 mg/mL was successfully prepared and characterized. The formulation showed rheological and mucoadhesive properties suitable for an Eosinophilic Esophagitis local prolonged treatment. In this way, pharmacists can prepare stable budesonide-based mucoadhesive solutions, providing both patients and physicians with a new therapeutic option for Eosinophilic Esophagitis pediatric treatment.

CROCuS, a Phase II Study Evaluating the Antiviral Activity, Clinical Outcomes, and Safety of Rilematovir in Children Aged ≥28 Days and ≤3 Years with Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) causes significant morbidity and mortality in children aged ≤5 years and adults aged ≥60 years worldwide. Despite this, RSV-specific therapeutic options are limited. Rilematovir is an investigational, orally administered inhibitor of RSV fusion protein-mediated viral entry. To establish the antiviral activity, clinical outcomes, safety, and tolerability of rilematovir (low or high dose) in children aged ≥28days and ≤3years with RSV disease. CROCuS was a multicenter, international, double-blind, placebo-controlled, randomized, adaptive phase II study, wherein children aged ≥28 days and ≤3 years with confirmed RSV infection who were either hospitalized (Cohort 1) or treated as outpatients (Cohort 2) were randomized (1:1:1) to receive rilematovir (low or high dose) or placebo. Study treatment was administered daily as an oral suspension from days 1 to 7, with dosing based on weight and age groups. The primary objective was to establish antiviral activity of rilematovir by evaluating the area under the plasma concentration-time curve of RSV viral load in nasal secretions from baseline through day 5. Severity and duration of RSV signs and symptoms and the safety and tolerability of rilematovir were also assessed through day 28 (±3). In total, 246 patients were randomized, treated, and included in the safety analysis population (Cohort 1: 147; Cohort 2: 99). Of these, 231 were included in the intent-to-treat-infected analysis population (Cohort 1: 138; Cohort 2: 93). In both cohorts, demographics were generally similar across treatment groups. In both cohorts combined, the difference (95% confidence interval) in the mean area under the plasma concentration-time curve of RSV RNA viral load through day 5 was -1.25 (-2.672, 0.164) and -1.23 (-2.679, 0.227) log10 copies∙days/mL for the rilematovir low-dose group and the rilematovir high-dose group, respectively, when compared with placebo. The estimated Kaplan-Meier median (95% confidence interval) time to resolution of key RSV symptoms in the rilematovir low-dose, rilematovir high-dose, and placebo groups of Cohort 1 was 6.01 (4.24, 7.25), 5.82 (4.03, 8.18), and 7.05 (5.34, 8.97) days, respectively; in Cohort 2, estimates were 6.45 (4.81, 9.70), 6.26 (5.41, 7.84), and 5.85 (3.90, 8.27) days, respectively. A similar incidence of adverse events was reported in patients treated with rilematovir and placebo in Cohort 1 (rilematovir: 61.9%; placebo: 58.0%) and Cohort 2 (rilematovir: 50.8%; placebo: 47.1%), with most reported as grade 1 or 2 and none leading to study discontinuation. The study was terminated prematurely, as the sponsor made a non-safety-related strategic decision to discontinue rilematovir development prior to full recruitment of Cohort 2. Data from the combined cohort suggest that rilematovir has a small but favorable antiviral effect of indeterminate clinical relevance compared with placebo, as well as a favorable safety profile. Safe and effective therapeutic options for RSV in infants and young children remain an unmet need. EudraCT Number: 2016-003642-93; ClinicalTrials.gov Identifier: NCT03656510. First posted date: 4 September, 2018.

Tailoring of Bilosomal Nanogel for Augmenting the Off-Label Use of Sildenafil Citrate in Pediatric Pulmonary Hypertension.

Pediatric pulmonary hypertension is a serious syndrome with significant morbidity and mortality. Sildenafil is widely used off-label in pediatric patients with pulmonary arterial hypertension. In this study, bile salt-stabilized nanovesicles (bilosomes) were screened for their efficacy to enhance the transdermal delivery of the phosphodiesterase type 5 inhibitor, sildenafil citrate, in an attempt to augment its therapeutic efficacy in pediatric pulmonary hypertension. A response surface methodology was implemented for fabricating and optimizing a bilosomal formulation of sildenafil (SDF-BS). The optimized SDF-BS formulation was characterized in terms of its entrapment efficiency (EE), zeta potential, vesicle size, and in vitro release profile. The optimized formula was then loaded onto hydroxypropyl methyl cellulose (HPMC) hydrogel and assessed for skin permeation, in vivo pharmacokinetics, and pharmacodynamic studies. The optimized SDF-BS showed the following characteristic features; EE of 88.7 ± 1.1%, vesicle size of 185.0 + 9.2 nm, zeta potential of -20.4 ± 1.1 mV, and efficiently sustained SDF release for 12 h. Skin permeation study revealed a remarkable improvement in SDF penetration from bilosomal gel compared to plain SDF gel. In addition, pharmacokinetic results revealed that encapsulating SDF within bilosomal vesicles significantly enhanced its systemic bioavailability (∼3 folds), compared to SDF oral suspension. In addition, pharmacodynamic investigation revealed that, compared to plain SDF gel or oral drug suspension, SDF-BS gel applied topically triggered a significant elevation (p < 0.05) in cGMP serum levels, underscoring the superior therapeutic efficacy of SDF-BS gel. Conclusively, bilosomes can be viewed as a promising nanocarrier for transdermal delivery of SDF that would grant higher therapeutic efficiency while alleviating the limitations encountered with SDF oral administration.

Atovaquone oral suspension USP 750 mg/5mL: recall due to microbial contamination

Atovaquone oral suspension USP 750 mg/5mL: recall due to microbial contamination

Simultaneous assay of pyrimethamine and methylparaben in extemporaneous pediatric suspensions by an isocratic stability-indicating UPLC-DAD method

Pyrimethamine (PYM) is an antiparasitic drug used in the treatment of congenital toxoplasmosis, available only as tablets. Therefore, preparing extemporaneous formulations and their quality control is essential for safe pediatric treatment. This study aimed to develop and validate a stability-indicating method by ultra-performance liquid chromatography (UPLC) to quantify PYM and methylparaben (MP) in extemporaneous oral suspension and evaluate its applicability to the tablets assay. The analytical conditions included RP-C18 column, mobile phase composed of 0.05 M acetate buffer pH 4.5 and organic mixture (acetonitrile:methanol), at 60:40 (v/v), flow rate of 0.2 mL/min, injection volume of 2 µL and detection at 272 nm. PYM was detected at 3.9 min and MP at 4.7 min, without interference of the degradation products or other excipients. Linearity was observed in the range of 0.5 to 25 μg/mL. The method showed accuracy (mean recovery between 98.0 and 102.0%) and precision (RSD < 2%) for suspension and tablets; the method was robust regarding the variations in the analytical conditions. The developed method met the requirements of current guidelines, was indicative of stability, and was suitable for PYM determination in extemporaneous preparations and tablets.

The pharmacokinetics of single-dose oral atorvastatin and its metabolites support therapeutic use in cockatiels (Nymphicus hollandicus).

To evaluate the plasma concentrations and determine the pharmacokinetic parameters of atorvastatin and its primary active metabolites (para- and orthohydroxyatorvastatin) after administration of a single oral dose in cockatiels (Nymphicus hollandicus). 14 adult cockatiels (7 male, 7 female) around 2 years of age. A compounded oral suspension of atorvastatin 10 mg/mL made with an oral suspending agent and an oral sweetener was administered via oral gavage at 20 mg/kg to each bird. Blood samples were collected at 7 different time points from 0.5 to 24 hours postadministration in a balanced incomplete block design with 3 blood samples per bird and 6 replicates per time point. Plasma concentrations of atorvastatin, parahydroxyatorvastatin, and orthohydroxyatorvastatin were determined by liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis was performed using noncompartmental analysis. The estimated time to maximum concentration (tmax) for atorvastatin, parahydroxyatorvastatin, and orthohydroxyatorvastatin was 3 hours for each. The estimated maximum plasma concentration (Cmax) for atorvastatin, parahydroxyatorvastatin, and orthohydroxyatorvastatin was 152.6, 172.4, and 68.8 ng/mL, respectively. The terminal half-lives were 4, 6.8, and 4.6 hours, respectively. These results support the therapeutic use of atorvastatin at the dose evaluated in this species based on human pharmacokinetic data. A starting dose of 20 mg/kg PO every 12 to 24 hours could be used to treat lipid disorders in cockatiels pending more data on multidose use and hypolipidemic efficacy.

Posaconazole in paediatric malignancy and haematopoietic stem cell transplant: dosing to achieve therapeutic concentration.

Posaconazole is increasingly used for the treatment and prophylaxis of invasive fungal infections in immunocompromised children. We aimed to review evidence for paediatric posaconazole dosing regimens focusing on attainment of target concentrations and frequency of adverse effects. In May 2023, the Cochrane, Embase, MEDLINE and PubMed databases were searched for articles reporting posaconazole dosing in children with malignancy or post-haematopoietic stem cell transplantation. Studies reporting the attainment of target serum concentrations were included. Overall, 24 studies were included. Eighteen studies of the oral suspension consistently reported poor attainment of target concentrations for prophylaxis (≥0.7 µg/mL, 12%-78%) despite high daily doses of 14-23 mg/kg/day (max. 1200 mg/day). Target attainment was significantly affected by gastric pH and food intake. Six studies of the delayed-release tablet (DRT) reported 58%-94% achieved concentrations ≥0.7 µg/mL, with the majority using lower doses of 4-12 mg/kg/day (max. 300 mg/day). Similarly, one study of powder for oral suspension found 67%-100% achieved target concentrations with a dose of 6 mg/kg/day (max. 300 mg/day). As expected, the IV formulation had high attainment of prophylaxis targets (81%-90%) with 6-10 mg/kg/day (max. 400 mg/day). All formulations were well tolerated, and no relationship between adverse effects and posaconazole concentrations was identified. The required posaconazole dose in immunocompromised children varies depending on the formulation. The IV infusion had the highest attainment of therapeutic concentration followed by the DRT and powder for suspension. By contrast, the oral suspension had low attainment of target concentrations despite higher daily doses.

Bioequivalence risk assessment of oral formulations containing racemic ibuprofen through a chiral physiologically based pharmacokinetic model of ibuprofen enantiomers

The characterization of the time course of ibuprofen enantiomers can be useful in the selection of the most sensitive analyte in bioequivalence studies. Physiologically based pharmacokinetic (PBPK) modelling and simulation represents the most efficient methodology to virtually assess bioequivalence outcomes. In this work, we aim to develop and verify a PBPK model for ibuprofen enantiomers administered as a racemic mixture with different immediate release dosage forms to anticipate bioequivalence outcomes based on different particle size distributions. A PBPK model incorporating stereoselectivity and non-linearity in plasma protein binding and metabolism as well as R-to-S unidirectional inversion has been developed in Simcyp®. A dataset composed of 11 Phase I clinical trials with 54 scenarios (27 per enantiomer) and 14,452 observations (7129 for R-ibuprofen and 7323 for S-ibuprofen) was used. Prediction errors for AUC0-t and Cmax for both enantiomers fell within the 0.8–1.25 range in 50/54 (93 %) and 42/54 (78 %) of scenarios, respectively. Outstanding model performance, with 10/10 (100 %) of Cmax and 9/10 (90 %) of AUC0-t within the 0.9–1.1 range, was demonstrated for oral suspensions, which strongly supported its use for bioequivalence risk assessment. The deterministic bioequivalence risk assessment has revealed R-ibuprofen as the most sensitive analyte to detect differences in particle size distribution for oral suspensions containing 400 mg of racemic ibuprofen, suggesting that achiral bioanalytical methods would increase type II error and declare non-bioequivalence for formulations that are bioequivalent for the eutomer.

BBD assisted in-situ nanoliposomes of esculin hydrate via intranasal delivery for the amelioration of Parkinson's disease

The objective of this research was to develop and optimise esculin Hydrate loaded nanoliposomes (ESH-NLs). The nanoliposomes were prepared by solvent evaporation method and optimized using a three-factor, three-level Box-Behnken design. Phospholipid 90G (X1), cholesterol (X2), and sonication time (X3) were used as independent variables, and their effects on vesicle size (Y1), entrapment efficiency (Y2), and Polydispersity index (Y3) were observed. The opt-ESH-NLs were further characterised for in-vitro drug release, DPPH assay, confocal laser scanning microscopy, and ex-vivo permeation. Opt-ESH-NLs had a vesicle size of 88.36 nm, a PDI of 0.06, an entrapment efficiency of 94.22 ± 0.93 %, and a drug release of 76.776 ± 1.127 %. Compared to standard ascorbic acid, the antioxidant activity was found to be 78.52 ± 0.148 %. Ex-vivo permeation studies revealed that opt-ESH-NLs had significantly enhanced permeation (79.484 ± 0.754 %) compared to ESH suspension (38.326 ± 1.279 %). Pharmacokinetic study revealed that opt-ESH-NLs when compared with Oral ESH suspension had a significant bioavailability in Brain as compared to plasma. The stability study of nanoliposomes at 4 °C reveals there is no significant change in the formulation. It was concluded that opt-ESH-NLs is a promising and effective formulation for intranasal administration for direct delivery of drug in the brain for amelioration of PD.

An eco-friendly spectrophotometric analysis tool with whiteness assessment to assay erythromycin in pharmaceutical formulation through metal complexation with Ni2+: application to the microbiological activity using agar diffusion method

A new, facile and eco-friendly spectrophotometric method for estimating erythromycin (ERY) in its dosage form has been proposed and validated. It depends on the formation of a complex between the drug and nickel at pH 7, using distilled water as a diluent, where the absorbance of the generated complex was measured at 228.5 nm. The formed complex followed a linear response over the concentration range of 80.0 to 300.0 µg/mL of ERY. The proposed method was fully validated according to international conference of harmonization (ICH) and was used to estimate the relevant concentration of the drug in its oral suspension formulation providing mean percentage recovery of 100.0±1.08 with a limit of detection and limit of quantification of 60 µg/mL and 80 µg/mL, respectively. the reaction stoichiometry was investigated and a reaction mechanism proposal was offered. Eventually, the antimicrobial effect of ERY and its metal complex with Ni2+ were compared using agar diffusion method, where no significant difference in their activities was observed.

Real-world safety study of posaconazole oral suspension in children under 13 years of age

Real-world safety study of posaconazole oral suspension in children under 13 years of age

Three-arm clinical trial of improved flour targeting intestinal microbiota (MALINEA).

The main objective of this project was to compare in the field conditions two strategies of re-nutrition of children with moderate acute malnutrition (MAM) aged from 6 to 24 months, targeting the microbiota in comparison with a standard regimen. A three-arm, open-label, pragmatic randomised trial was conducted in four countries (Niger, CAR, Senegal and Madagascar). Children received for 12 weeks either fortified blended flour (FBF control) = arm 1, or FBF + azithromycin (oral suspension of 20 mg/kg/day daily given with a syringe) for the first 3 days at inclusion = arm 2 or mix FBF with inulin/fructo-oligosaccharides (6 g/day if age ≥12 months and 4 g if age <12 months) = arm 3. For each arm, children aged from 6 to 11 months received 100 g x 2 per day of flours and those aged from 12 to 24 months received 100 g × 3 per day of FBF. The primary endpoint was nutritional recovery, defined by reaching a weight-for-height z-score (WHZ) ≥ -1.5 within 12 weeks. Overall, 881 children were randomised (297, 290 and 294 in arm 1, arm 2 and arm 3, respectively). Three hundred and forty-four children were males (39%) and median/mean age were 14.6/14.4 months (SD = 4.9, IQR = 10.5-18.4). At inclusion, the three arms were comparable for all criteria, but differences were observed between countries. Overall, 44% (390/881) of the children recovered at week 12 from MAM, with no significant difference between the three arms (41.4%, 45.5% and 45.9%, in arm 1, arm 2 and arm 3, respectively, p = 0.47). This study did not support the true advantages of adding a prebiotic or antibiotic to flour. When using a threshold of WHZ ≥ -2 as an exploratory endpoint, significant differences were observed between the three arms, with higher success rates in arms with antibiotics or prebiotics compared to the control arm (66.9%, 66.0% and 55.2%, respectively, p = 0.005).

Combination of the Topical Photodynamic Therapy of Chloroaluminum Phthalocyanine Liposomes with Fexinidazole Oral Self-Emulsifying System as a New Strategy for Cutaneous Leishmaniasis Treatment.

Cutaneous leishmaniasis (CL) is a neglected tropical disease. The treatment is restricted to drugs, such as meglumine antimoniate and amphotericin B, that exhibit toxic effects, high cost, long-term treatment, and limited efficacy. The development of new alternative therapies, including the identification of effective drugs for the topical and oral treatment of CL, is of great interest. In this sense, a combination of topical photodynamic therapy (PDT) with chloroaluminum phthalocyanine liposomes (Lip-ClAlPc) and the oral administration of a self-emulsifying drug delivery system containing fexinidazole (SEDDS-FEX) emerges as a new strategy. The aim of the present study was to prepare, characterize, and evaluate the efficacy of combined therapy with Lip-ClAlPc and SEDDS-FEX in the experimental treatment of Leishmania (Leishmania) major. Lip-ClAlPc and SEDDS-FEX were prepared, and the antileishmanial efficacy study was conducted with the following groups: 1. Lip-ClAlPc (0.05 mL); 2. SEDDS-FEX (50 mg/kg/day); 3. Lip-ClAlPc (0.05 mL)+SEDDS-FEX (50 mg/kg/day) combination; 4. FEX suspension (50 mg/kg/day); and 5. control (untreated). BALB/c mice received 10 sessions of topical Lip-ClAlPc on alternate days and 20 consecutive days of SEDDS-FEX or FEX oral suspension. Therapeutical efficacy was evaluated via the parasite burden (limiting-dilution assay), lesion size (mm), healing of the lesion, and histological analyses. Lip-ClAlPc and SEDDS-FEX presented physicochemical characteristics that are compatible with the administration routes used in the treatments. Lip-ClAlPc+SEDDS-FEX led to a significant reduction in the parasitic burden in the lesion and spleen when compared to the control group (p < 0.05) and the complete healing of the lesion in 43% of animals. The Lip-ClAlPc+SEDDS-FEX combination may be promising for the treatment of CL caused by L. major.