Oral Suspension Research Articles

Facilitators and barriers to infant post-natal HIV prophylaxis, a qualitative sub-study of the PROMISE-EPI trial in Lusaka, Zambia.

Infant post-natal prophylaxis (PNP) is used to prevent HIV transmission through breastfeeding. The WHO edited recommendations but so far there is no consensus on the duration of prophylaxis and the type of drug used depends on national guidelines. In Zambia, the national recommendations include a three-drug prophylaxis, composed of a dispersible combined tablet of zidovudine (AZT) and lamivudine (3TC) and an oral suspension of nevirapine (NVP) for 12 weeks or until the mother's viral load is <1,000 cp/mL. The PROMISE-EPI study, modified the PNP regimen to lamivudine only, initiated at 6 weeks and continued until 12 months to all HIV exposed uninfected infants of virally unsuppressed mothers. Our aim in this analysis was to identify barriers and facilitators to this extended PNP, the keystone toward an effective prevention. Individual interviews and focus group discussion (FGD) were conducted with PROMISE-EPI participants who had received prophylaxis for their children from the national program up to 6 weeks and then lamivudine oral solution in PROMISE-EPI study. Health care providers and PROMISE-EPI staff were also interviewed. Sessions were recorded, transcribed verbatim and translated from local languages into English. An initial code-book was designed and then adapted on the basis of the emerging themes, to allow a descriptive thematic analysis. More barriers to PNP adherence were identified with triple drug prophylaxis than with lamivudine. These barriers were related to the formulation and bitter taste of AZT/3TC tablets. The ready to use formulation and sweet taste of lamivudine syrup were appreciated by mothers. Extended PNP proposed in the PROMISE-EPI study was globally well accepted and strategies were found to increase adherence. Adherence to lamivudine appeared to be better than the mothers' adherence to their own antiretroviral therapy. Accompanying mothers living with HIV and giving them the choice of the PNP to prevent transmission via breastfeeding (type of PNP regimen and extended PNP in non-adherent mothers), may be one of the keys to reducing the burden of pediatric HIV acquisition in low and middle income countries.

Levodropropizine: A promising peripherally acting antitussive agent

Cough is one of the most frequent symptom for patients to seek medical attention. Cough can be associated with many disease processes and the ultimate treatment depends on determining the etiology and diagnosis. Antitussive agents with different mechanisms of action have been developed in the past, but there are still very few medications that seem to be effective without any side effects especially related to central nervous system (CNS). Levodropropizine is an antitussive agent which acts peripherally and is a non-opioid cough medication that is in use since many years as a symptomatic therapy for cough. Levodropropizine has potent antitussive activity mainly due to peripheral effects by inhibiting the activation of vagal C-fibers. In fact, levodropropizine has been proven effective in controlling cough and is devoid of the central depressant effect. Levodropropizine oral suspension (30mg/5ml) is approved by drug approval body of India, Drug Controller General of India (DCGI) for the management non-productive cough in adults. Levodropropizine is approved in some of the European countries and in Asian countries. It is widely used in Republic of Korea for the symptomatic treatment of cough in both adults and children above 2 years of age. Levodropropizine has the utmost level of benefit in comparison with central antitussive agents namely codeine and dextromethorphan for the patients with cough due to acute and chronic bronchitis.

5-Aminolevulinic Acid Fluorescence-Guided Surgery in Head and Neck Squamous Cell Carcinoma.

To determine the utility of 5-aminolevulinic acid (5-ALA) fluorescence for resection of head and neck carcinoma. In this prospective pilot trial, 5-ALA was administered as an oral suspension 3-5 h prior to induction of anesthesia for resection of head and neck squamous cell carcinoma (HNSCC). Following resection, 405 nm blue light was applied, and fluorescence of the tumor as well as the surgical bed was recorded. Specimen fluorescence intensity was graded categorically as none (score = 0), mild (1), moderate (2), or robust (3) by the operating surgeon intraoperatively and corroborated with final pathologic diagnosis. Seven patients underwent resection with 5-ALA. Five (83%) were male with an age range of 33-82 years (mean = 60). Sites included nasal cavity (n = 3), oral cavity (n = 3), and the larynx (n = 1). All specimens demonstrated robust fluorescence when 5-ALA was administered 3-5 h preoperatively. 5-ALA fluorescence predicted the presence of perineural invasion, a positive margin, and metastatic lymphadenopathy. Two patients had acute photosensitivity reactions, and one patient had a temporary elevation of hepatic enzymes. 5-ALA induces robust intraoperative fluorescence of HNSCC, capable of demonstrating a positive margin, perineural invasion, and metastatic nodal disease. Although no conclusions are there about the safety of this drug in the head and neck cancer population, our study parallels the extensive safety data in the neurosurgical literature. Future applications may include intraoperative assessment of margin status, diagnostic accuracy, and impacts on survival. 4 Laryngoscope, 134:741-748, 2024.

Compatibility study of patiromer with juices/liquids and soft foods

Patiromer powder for oral suspension (patiromer o.s.) is a once-daily, potassium (K+) binder approved for the treatment of hyperkalemia. It is known that patiromer o.s. can be mixed with water, apple juice, or cranberry juice. This in vitro study assessed whether mixing patiromer o.s. with a variety of other liquids and soft foods would affect the total K+-exchange capacity (TKEC) of patiromer. Juices (grape, orange, pear, or pineapple), nectars (apricot or peach), and other liquids/soft foods (milk, thickener, apple sauce, chocolate pudding, vanilla pudding, or yoghurt) were assessed for compatibility with patiromer o.s. at low and high ratio levels, equivalent to patiromer active moiety doses of 8.4 g and 25.2 g per 80 mL (1/3 cup), respectively. Mixtures were stirred, rested for 45 min, diluted with water, and centrifuged. Residues were washed, vacuum filtered, and dried. TKEC of the residue was evaluated; the prespecified acceptance criterion for patiromer was 8.4–10.0 mmol/g. Mean TKECs of the patiromer in juices/nectars were 8.7–8.9 mmol/g for the low ratio and 8.5–8.6 mmol/g for the high ratio. For other liquids/soft foods, the mean TKEC for patiromer at low and high ratios was 8.5–8.7 mmol/g. All tested vehicles were within the prespecified range. Mixing of patiromer o.s. with juices/liquids and soft foods does not adversely affect the K+-binding capability of patiromer. Use of different vehicles for suspending patiromer o.s. may help with its palatability, enhance patient experience, and reduce nonadherence.Graphical The potassium binder, patiromer powder for oral suspension, can be mixed with water, juices (apple, cranberry, grape, orange, pear, or pineapple), nectar (apricot or peach), other liquids (milk or thickener), and soft foods (apple sauce, chocolate or vanilla pudding, or yoghurt) for the treatment of hyperkalemia.

Posaconazole exposure in critically ill ICU patients: a need for action

PurposePosaconazole is an antifungal drug currently being used for prophylaxis and treatment of invasive fungal infections such as aspergillosis. To date, therapeutic drug monitoring (TDM) of posaconazole is recommended with the use of oral suspension, but the potential need of TDM with the use of IV formulations is rising. Therefore, we aimed to investigate the pharmacokinetics of IV posaconazole in critically ill patients.MethodsIn a prospective study, we analysed 168 consecutivelly collected posaconazole levels from 10 critically ill patients drawn during a 7 day curse. Posaconazole concentrations were measured using a chromatographic method. Demographic and laboratory data were collected, and the data was analysed using descriptive statistics.ResultsWe included 168 posaconazole levels, resulting in a median trough of 0.62 [0.29–1.05] mg/L with 58% not reaching the suggested target of 0.5 mg/L for fungal prophylaxis. Moreover, 74% of the trough levels were under the target of 1 mg/L which is proposed for the treatment of aspergillosis.ConclusionPosaconazole exposure is highly variable in critically ill patients resulting in potentially insufficient drug concentrations in many cases. TDM is highly recommended to identify and avoid underexposure.Trial registration numberNCT05275179, March 11, 2022.

Comparison of drugs for active eosinophilic oesophagitis: systematic review and network meta-analysis

BackgroundThere is currently no recommendation regarding preferred drugs for active eosinophilic oesophagitis (EoE) because their relative efficacy is unclear. We conducted an up-to-date network meta-analysis to compare proton pump inhibitors,...

Formulation and Evaluation of Ornidazole Oral Re-Constitutable Suspension

Large numbers of drugs are available in the market in form of dry syrup, where reconstitution has to be done by patient. Ornidazole is an antibiotic used to treat some protozoan infections. It has also been investigated for use in Crohn's disease after bowel resection. In the present investigation the drug Ornidazole was selected for the design of oral reconstitutable suspension for improving its stability and palatability by using various techniques like physical mixing, solvent evaporation and co-grinding method with different suspending agents like Xanthan gum, SCMC, Guar gum and sodium alginate. The reconstitutable suspensions were evaluated for flow properties, particle size, pH, viscosity, sedimentation volume, redispersibility and drug release by in-vitro dissolution studies. Formulated OFS reconstitutable suspension has acceptable sedimentation properties. The drug excipients interactions and crystal morphology of optimized reconstitutable suspension were evaluated by Fourier transform infrared spectroscopy (FTIR), differential scanning Calorimetry (DSC), analysis. The results indicated that the release of the Ornidazole was rapid from all formulations than the pure drug. The drug release from the suspensions followed first order kinetics. From the results it is concluded that effective taste masking of Ornidazole was achieved using SCMC and successfully evaluated in reconstitutable suspension.

Low-dose perinatal supplementation with Enterococcus faecalis increases concentrations of short-chain fatty acids in the offspring but does not protect against allergic asthma.

Childhood allergic asthma is associated with a dysbiotic gut microbiome in early life, and maternal perinatal treatment with probiotics is a potential way alter the infant microbiome, which may improve asthma outcomes. This study used a mouse model to examine the effect of maternal supplementation with the probiotic Enterococcus faecalis on faecal short-chain fatty acid (SCFA) concentrations and asthma risk in the offspring. Pregnant/lactating mice were treated daily, from gestation day 6 to postnatal day 21, with an oral suspension of 106, 107 or 108 colony-forming units of a live preparation of the probiotic E. faecalis (Symbioflor®1). At weaning, offspring were subjected to an ovalbumin-induced experimental asthma protocol. Faeces were collected from the mothers and offspring at several different time points to determine SCFA concentrations. It was found that maternal supplementation with E. faecalis did not alter litter size, sex ratio or offspring weight, and was associated with an increase in SCFAs in offspring faeces at weaning and after allergy induction. However, allergic offspring from E. faecalis supplemented mothers showed no difference in asthma severity when compared with allergic offspring from control mothers. In conclusion, although maternal perinatal supplementation with low-dose E. faecalis was associated with increased faecal SCFAs in the offspring, it did not protect against offspring asthma. This is may be because SCFA concentrations were not increased to an immunoprotective level. We recommend that future studies concentrate on probiotic supplementation in high-risk cases, for instance, to repair gut dysbiosis resulting from antibiotic use in pregnant mothers or their infants.

FORMULATION AND EVALUATION OF CEFUROXIME AXETIL GRANULES FOR ORAL SUSPENSION

Objectives: The aim of this study is formulation and evaluation of cefuroxime axetil (CA) granules for oral suspension and to compare its in vitro bioavailability with Innovator Product. Methods: The granules of CA were prepared by wet granulation method. Six formulations of varying composition of ingredients were prepared. Preformulation studies were performed. The suspension was evaluated for its flow property, in vitro dissolution study, and assay. Results: Preformulation parameters show that the flow property of powder is poor. The suspension was successfully prepared by wet granulation method. The flow property of granules varied form fair to excellent in different formulations. The f2value ranges from 25 to 77. Conclusion: With a better release characteristic and excellent flow property, the formulation F6 is considered as the final formulation with an f2 value of 77 and assay of 99.7%.

Candida-related lesions dalam rongga mulut: diagnosis dan strategi penatalaksanaanya

Background: Candida–related lesions can present as denture sore mouth intraorally and cheilitis angular extra orally. Some predisposing factors include ill-fitting dentures, malnutrition, and poor oral hygiene. Objective: To determine the proper diagnosis and management of sore mouth dentures and cheilitis angular in patients with ill-fitting dentures and bad oral hygiene. Case report: A 59-year-old male patient presented with a burning sensation on the hard palate and sores at the corners of the lips, which were aggravated by the meal and opening of the mouth. No history of systemic diseases was found. Extra-orally erythema fissure lesions were found surrounded by multiple white areas at the corners of the lips bilaterally and were painful. Intra-oral examination showed erythema macular lesions that extend to the gingiva and palate mucosa that contact the denture base. Nystatin oral suspension combined with fluconazole, and multivitamins as supportive therapy. Educational suggestions such as the replacement of dentures and improve oral hygiene conditions were given. Conclusion: Denture sore mouth and cheilitis angular in this case are caused by Candida albicans related to the insufficient denture and poor oral hygiene. Management for this case by providing causative treatment with single or combine antifungal drugs along with proper communication, instructions, and education regarding the diseases.

Development and validation of a simple microwave-assisted digestion sample preparation technique for the estimation of aluminium and magnesium in a few pharmaceutical dosage forms by an inductively coupled-mass spectrometer (ICP-MS).

Rationale: A simple, sensitive, reliable, validated, inductively coupled plasma mass spectrometric method for the determination of aluminium and magnesium using a simple common microwave-assisted digestion sample preparation technique for a few commonly used formulations was developed and validated according to International Conference on Harmonization Q3D and the United States Pharmacopeia general chapter <232> and <233>. The following pharmaceutical dosage forms were considered for estimation of aluminium and magnesium: Alumina, magnesia simethicone oral suspension, Alumina, magnesia simethicone chewable tablets, alumina and magnesia oral suspension, alumina and magnesium carbonate oral suspension. Methods: The methodology included optimizing a common microwave assisted digestion method, selecting the isotopes, choosing the measurement technique, and designating internal standards. The finalized microwave assisted procedure was a two-step program where in the first step the samples were ramped for 10 min to a temperature of 180 °C and hold for 5 min followed by ramping for 10 min to a temperature of 200 °C and hold for 10 min. Magnesium (24Mg) and aluminium (27Al) isotopes were finalized, internal standard assigned for both the isotopes was yttrium (89Y) with Helium (kinetic energy discrimination-KED) as the measuring mode. System suitability was run before initiating analysis to ensure that system performance was consistent. Results: Analytical validation parameters like specificity, linearity (from 25% to 200% of sample concentration), the detection limit and the limit of quantification were established. For all these dosage forms, the method's precision was demonstrated by analyzing the percentage relative standard deviation for six injections. Accuracy was established from 50% to 150% of instrument working concentration (J-levels) for aluminium and magnesium for all the formulations and was found to be within the range of 90-120%. Conclusion: This common analysis method, along with the common microwave-digestion technique applies to numerous types of matrices for a finished dosage form with aluminium and magnesium.

Pharmacokinetics and Safety of Sulfamethoxazole-Trimethoprim After Oral Administration of Single and Multiple Doses to Rhode Island Red Chickens (Gallus gallus domesticus).

Sulfamethoxazole-trimethoprim (SMZ-TMP), a commonly prescribed antibiotic for backyard hens, is neither Food and Drug Administration approved nor prohibited in laying hens in the United States. The aim of this study was to determine whether plasma concentrations above targeted minimum inhibitory concentration breakpoint values for Enterobacteriaceae could be achieved with oral dosing. Five Rhode Island red hens (Gallus gallus domesticus) were administered a single dose of 96 mg/kg SMZ-TMP (80 mg/kg SMZ and 16 mg/kg TMP) IV followed by the same dose orally after a washout period. Following oral dosing, mean SMZ concentrations exceeded the target breakpoint for approximately 12 hours; however, TMP only briefly exceeded the target breakpoint. Bioavailability was 60.5% for SMZ and 82.0% for TMP. Ten naïve birds were allocated into control (n = 4) and treatment (n = 6) groups for a 7-day multi-dose study. Treatment birds received an oral suspension dosed at 16 mg/kg TMP and 80 mg/kg SMZ every 48 hours (on days 1, 3, 5, and 7); TMP tablets were additionally dosed at 25 mg/bird on days 1, 3, 5, and 7, and 50 mg/bird on days 2, 4, and 6. Plasma SMZ-TMP concentrations were measured on a multiple time interval by ultraperformance liquid chromatography-mass spectrometry, and pharmacokinetic analyses were performed using a noncompartmental model. No accumulation for either drug was noted following repeated dosing, and no statistical differences in biochemical values, packed cell volumes, or weight were found between pre- and posttreatment in either the treatment or control groups. Sulfamethoxazole (80 mg/kg q48h PO) and TMP (24.1-28.0 mg/kg q24h PO) maintained therapeutic plasma concentrations at or exceeding the minimum inhibitory concentration breakpoint of Enterobacteriaceae for 72 and 24 hours for TMP and SMZ, respectively, without evidence of adverse effects or drug accumulation. Further studies are needed to refine this dosage regimen and evaluate adverse effects in ill birds.

Valuable effects of lactobacillus and citicoline on steatohepatitis: role of Nrf2/HO-1 and gut microbiota

Non-alcoholic steatohepatitis (NASH) is a more dangerous form of chronic non-alcoholic fatty liver disease (NAFLD). In the current investigation, the influence of citicoline on high-fat diet (HFD)-induced NASH was examined, both alone and in combination with Lactobacillus (probiotic). NASH was induced by feeding HFD (10% sugar, 10% lard stearin, 2% cholesterol, and 0.5% cholic acid) to rats for 13 weeks and received single i.p. injection of streptozotocin (STZ, 30 mg/kg) after 4 weeks. Citicoline was given at two dose levels (250 mg and 500 mg, i.p.) at the beginning of the sixth week, and in combination with an oral suspension of Lactobacillus every day for eight weeks until the study’s conclusion. HFD/STZ induced steatohepatitis as shown by histopathological changes, elevated serum liver enzymes, serum hyperlipidemia and hepatic fat accumulation. Moreover, HFD convinced oxidative stress by increased lipid peroxidation marker (MDA) and decreased antioxidant enzymes (GSH and TAC). Upregulation of TLR4/NF-kB and the downstream inflammatory cascade (TNF-α, and IL-6) as well as Pentaraxin, fetuin-B and apoptotic markers (caspase-3 and Bax) were observed. NASH rats also had massive increase in Bacteroides spp., Fusobacterium spp., E. coli, Clostridium spp., Providencia spp., Prevotella interrmedia, and P. gingivalis while remarkable drop in Bifidobacteria spp. and Lactobacillus spp. Co-treatment with citicoline alone and with Lactobacillus improve histopathological NASH outcomes and reversed all of these molecular pathological alterations linked to NASH via upregulating the expression of Nrf2/HO-1 and downregulating TLR4/NF-kB signaling pathways. These results suggest that citicoline and lactobacillus may represent new hepatoprotective strategies against NASH progression.

Sodium Phenylbutyrate and Taurursodiol: A New Therapeutic Option for the Treatment of Amyotrophic Lateral Sclerosis.

To review the safety and efficacy of sodium phenylbutyrate and taurursodiol (SP + T) in slowing progression of amyotrophic lateral sclerosis (ALS) compared with pre-existing therapies. A PubMed (from January 1, 2009, to April 13, 2023) and ClinicalTrials.gov search conducted using sodium phenylbutyrate, taurursodiol, AMX0035, riluzole, and edaravone. Additional articles were identified by hand from references. This included English-language articles evaluating SP + T efficacy or safety in humans for decreasing neuronal death and slowing the progression of ALS. In one phase II clinical trial that encompassed an open-label extension phase, disease severity, assessed by the rate of decline in overall score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised with higher scores indicating more functional ability, was -1.24 points per month with active drug and -1.66 points per month with placebo (difference, 0.42 points per month; 95% CI, 0.03-0.81; P = 0.03). Post hoc analysis found survival benefit of median 4.8 months with active medication compared with placebo. SP + T is a new US Food and Drug Administration-approved oral suspension for the treatment of ALS. Patients who received active medication through the phase II trial showed decreased rates of disease progression. Overall, SP + T could be considered a potential agent for the treatment of ALS which has a high unmet need. SP + T is an option for the treatment of ALS; however, additional data regarding efficacy in phase III trials with long-term safety profile considerations, as well as trials to compare current therapy with SP + T, are needed.

A novel abiraterone acetate oral suspension for patients with metastatic prostate cancer: An open-label, phase 3, randomized trial.

5052 Background: Abiraterone acetate (AA) is a first-line oral hormone therapy for metastatic prostate cancer (mPC), but the licensed formulation is limited by large tablet size, requirement to take on an empty stomach, and pharmacokinetic variability. TAVT-45, a novel formulation of AA granules for oral suspension, offers improved oral bioavailability (allowing dose reduction), decreased food effect, and may provide an option for the ~20-30% of patients with dysphagia. This Phase 3, open-label global study (NCT04887506) aimed to establish therapeutic equivalence between TAVT-45 granules and reference AA tablets (R-AA). Methods: Patients with castrate-resistant or castrate-sensitive mPC (mCRPC or mCSPC) were randomized 1:1 to receive TAVT-45 (1 sachet of AA granules [250 mg] in water or juice, twice daily) or R-AA tablets (2 x 500 mg once daily ≥1 h before or ≥2 h after food), plus prednisone (5 mg once [mCSPC] or twice [mCRPC] daily) for 84 days. Efficacy (serum testosterone and prostate-specific antigen [PSA]) and safety were assessed. Average serum testosterone concentrations on Days 9 &amp; 10 (primary endpoint, analyzed via analysis of covariance) were compared to show therapeutic equivalence. The key secondary endpoint was PSA-50 response (patients with ≥50% decrease in PSA from baseline at any time). mCRPC was the primary analysis population. Preliminary results are presented. Results: Of 107 randomized patients, 103 received TAVT-45 (n=54) or R-AA (n=49). The TAVT-45 and R-AA groups were well matched (mean [SD] age: 74.5 [8.45] and 74.9 [8.40] years; mCRPC: 61.1% and 61.2%). In mCRPC, serum testosterone concentrations fell rapidly from mean (SD) baseline of 9.7 (5.19) for TAVT-45 and 10.6 (7.32) ng/dL for R-AA, with all &lt;1 ng/dL by Day 9. Therapeutic equivalence between TAVT-45 and R-AA at Days 9 &amp; 10 was also shown in the full study population: Days 9 &amp; 10 average rounded-up least-squares mean serum testosterone levels were comparable (TAVT-45 [n=52]: 1.004 ng/dL; R-AA [n=47]: 1.015 ng/dL), and the geometric mean ratio between groups was 0.990 (90% CI: 0.978-1.002), with the 90% CI falling within 80.0–125.0% equivalence limits. No statistical difference between TAVT-45 vs R-AA was demonstrated for PSA-50 (mCRPC 85% vs 70%; mCSPC 90% vs 95%). The frequency of treatment-emergent adverse events (TEAEs) was similar between groups; most were mild or moderate. Serious TEAEs occurred in 5 TAVT-45 and 3 R-AA patients. There were two deaths in treated patients due to cardiorespiratory arrest (TAVT-45) and prostate cancer (R-AA); neither was considered related to study drug. Conclusions: This Phase 3 study demonstrates that TAVT-45, a novel AA formulation with improved bioavailability, yields similar testosterone/PSA responses and a comparable safety profile to R-AA, and as an oral solution, may be suitable for mPC patients with dysphagia. Clinical trial information: NCT04887506 .

Model Based Estimation of Posaconazole Tablet and Suspension Bioavailability in Hospitalized Children Using Real-World Therapeutic Drug Monitoring Data in Patients Receiving Intravenous and Oral Dosing.

Invasive fungal infections are a major cause of morbidity and mortality for immunocompromised patients. Posaconazole is approved for treatment and prophylaxis of invasive fungal infection in adult patients, with intravenous, oral suspension, and gastroresistant/delayed-released tablet formulations available. In Europe, until very recently, posaconazole was used off-label in children, although a new delayed-release suspension approved for pediatric use is expected to become available soon. A population pharmacokinetic model was developed which uses posaconazole therapeutic drug monitoring data following intravenous and oral dosing in hospitalized children, thus enabling estimation of pediatric suspension and tablet oral bioavailability. In total, 297 therapeutic drug monitoring plasma levels from 104 children were included in this analysis. The final model was a one-compartment model with first-order absorption and nonlinear elimination. Allometric scaling on clearance and volume of distribution was included a priori. Tablet bioavailability was estimated to be 66%. Suspension bioavailability was estimated to decrease with increasing doses, ranging from 3.8% to 32.2% in this study population. Additionally, concomitant use of proton pump-inhibitors was detected as a significant covariate, reducing suspension bioavailability by 41.0%. This is the first population pharmacokinetic study to model posaconazole data from hospitalized children following intravenous, tablet, and suspension dosing simultaneously. The incorporation of saturable posaconazole clearance into the model has been key to the credible joint estimation of tablet and suspension bioavailability. To aid rational posaconazole dosing in children, this model was used alongside published pharmacodynamic targets to predict the probability of target attainment using typical pediatric dosing regimen.

СТРУКТУРНЫЙ АНАЛИЗ И ОЦЕНКА РАЦИОНАЛЬНОСТИ НАЗНАЧЕНИЙ ЛЕКАРСТВЕННЫХ ПРЕПАРАТОВ В ПЕДИАТРИЧЕСКОЙ ПРАКТИКЕ

This article discusses the problems of providing drug care to children. The aim of the work was to identify the prerequisites for the creation of a Russian indicative list of medicines for children based on the assessment of rationality and structural analysis of drug prescriptions in pediatric practice. The study used the methods of content analysis, statistical analysis, graphical method. The sample consisted of 2,900 prescriptions for drugs and other pharmacy products made by doctors of various profiles to children aged 0 to 17 years. The study showed that 92% were medicines (MP), the rest - other pharmacy products (biologically active additives, cosmetics, medical products, etc.). An analysis was also carried out by the frequency of prescriptions, by dosage forms, by anatomical-therapeutic-chemical (ATC) classification and by prescriptions outside the instructions (off-label, in our study, we attributed to off-label those cases when drugs were prescribed to children aged , not officially permitted in the instructions for medical use). Nurofen for children (Ibuprofen) oral suspension was the most frequently prescribed medication in the study sample. When analyzing according to the first level of the ATC classification, the largest percentage of prescriptions fell on group R - "Respiratory system". From the sample studied by us, most often children were prescribed drugs in liquid dosage forms, namely, drops for oral administration, in off-label prescriptions, for the most part, solid dosage forms (tablets) were found. It was found that in most cases drugs were prescribed outside the instructions for children aged 1 to 3 years - 39% of all off-label prescriptions. In our opinion, to improve the pharmaceutical care provided to children, it is necessary to create a Russian indicative list of essential medicines for children, which should be periodically reviewed and republished in order to contain only relevant and reliable information.

Quality and Stability Evaluation of Extemporaneously Compounded Losartan Potassium Oral Suspension at the Hospital Pharmacy

Aims: The purpose of this study was to evaluate the quality of an extemporaneous formulation of losartan potassium oral suspensions from crushed losartan potassium tablets to ensure that the compounded suspension maintained its quality attributes during its storage period.&#x0D; Methodology: Losartan potassium suspensions were compounded extemporaneously in the same way they are prepared for patients at a hospital pharmacy. The suspensions were kept in the refrigerator at 4°C and evaluated immediately and after 9, 18, and 28 days. Suspension ease of redispersion, color, odor, pH, particle size, zeta potential, viscosity, and sedimentation volume were all evaluated. In addition, microbiological stability, drug content, and drug dissolution were assessed.&#x0D; Results: During the study period, the extemporaneously compounded suspension retained its color and odor, and the pH profile remained consistent. Moreover, all suspensions were easily resuspended in a homogeneous liquid with gentle shaking, and no caking was detected. Furthermore, the results of the microbiological test revealed no microbial growth. The content uniformity and dissolution test results met the pharmacopeial requirements. The findings revealed that the losartan potassium compounding procedure was reliable and capable of producing 2.5 mg/mL of losartan potassium suspension using commercially available tablets and Ora-Blend as a suspending vehicle. Furthermore, after 28 days in the refrigerator (4°C), the suspension had acceptable quality features.&#x0D; Conclusion: Extemporaneously compounded suspension allows physicians to prescribe a variable dose that adjusts to each patient’s needs, providing treatment when the liquid dosage form is unavailable.

Assessment of quality of essential medicines in public health care facilities of Nepal: Findings of nationwide study.

Essential medicines are those medicines that satisfy the primary health care needs of the citizens. Poor quality of essential medicines can have serious impact on public health. Thus, this study is aimed to assess the quality of essential medicines available in public health care facilities of Nepal. A cross sectional descriptive study was carried out in 62 health facilities across 21 districts, representing all seven provinces of Nepal and selected proportionately from all three ecological regions i.e. Terai, Hill and Mountain using lottery method. Health facilities in selected districts were chosen using random number generator. Face to face interview was taken with health facility in charge using structured questionnaire. All storage conditions information was recorded through observation checklists. Temperature and humidity were measured using a digital instrument. Similarly, 20 different generic medicines were collected for quality testing. The obtained data were entered in Epidata version 3.1, cleaned in Microsoft Excel 2007 and analyzed in SPSS version 16.0. Among 62 health facilities, only 13% of health facilities were found to follow the medicine storage guidelines, with temperature and humidity levels exceeding recommended limits. Out of 244 batches of 20 different generics of essential medicines, 37 batches were found to be substandard. These substandard medicines were- Ciprofloxacin hydrochloride eye/ear drop, Iron supplement tablets, Metformin Hydrochloric tablet, Metronidazole Tablets, Paracetamol Oral suspension, Paracetamol tablet and Povidone Iodine solution. The study recommends the urgent need for the Government of Nepal to prioritize ensuring the quality of essential medicines in the country.

Atorvastatin-loaded pro-nanolipospheres with ameliorated oral bioavailability and antidyslipidemic activity

Despite significant advances in oral drug delivery technologies, many drugs are prone to limited oral bioavailability due to biological barriers that hinder drug absorption. Pro-nanolipospheres (PNL) are a form of delivery system that can potentiate the oral bioavailability of poorly water-soluble drugs through a variety of processes, including increased drug solubility and protecting them from degradation by intestinal or hepatic first-pass metabolism. In this study, pro-nanolipospheres were employed as a delivery vehicle for improving the oral bioavailability of the lipophilic statin, atorvastatin (ATR). Various ATR-loaded PNL formulations, composed of various pharmaceutical ingredients, were prepared by the pre-concentrate method and characterized by determining particle size, surface charge, and encapsulation efficiency. An optimized formula (ATR-PT PNL) showing the smallest particle size, highest zeta potential, and highest encapsulation efficiency was selected for further in vivo investigations. The in vivo pharmacodynamic experiments demonstrated that the optimized ATR-PT PNL formulation exerted a potent hypolipidemic effect in a Poloxamer® 407-induced hyper-lipidaemia rat model by restoring normal cholesterol and triglyceride serum levels along with alleviating serum levels of LDL while elevating serum HDL levels, compared to pure drug suspensions and marketed ATR (Lipitor®). Most importantly, oral administration of the optimized ATR-PT PNL formulation showed a dramatic increase in ATR oral bioavailability, as evinced by a 1.7- and 3.6-fold rise in systemic bioavailability when compared with oral commercial ATR suspensions (Lipitor®) and pure drug suspension, respectively. Collectively, pro-nanolipospheres might represent a promising delivery vehicle for enhancing the oral bioavailability of poorly water-soluble drugs.