Impact of Mucositis on Absorption and Systemic Drug Exposure of Isavuconazole

ABSTRACT Isavuconazonium sulfate is the water-soluble prodrug of isavuconazole. Population analyses have demonstrated relatively predictable pharmacokinetic (PK) behavior in diverse patient populations. We evaluated the impact of mucositis on the oral isavuconazole exposure using population PK modeling. This study included patients treated in two phase 3 trials of isavuconazole, SECURE for treatment of invasive aspergillosis (IA) and other filamentous fungi and VITAL for patients with mucormycosis, invasive fungal disease (IFD) caused by other rare fungi, or IA and renal impairment. Mucositis was reported by site investigators and its impact on oral bioavailability was assessed. Use of the oral formulation was at the discretion of the investigator. Patients with plasma samples collected during the use of isavuconazonium sulfate were included in the construction of population PK model. Of 250 patients included, 56 patients had mucositis at therapy onset or as an adverse event during oral isavuconazole therapy. Levels of oral bioavailability were comparable, at 98.3% and 99.8%, respectively. The average drug exposures (average area under the curve [AUCave]) calculated from either the mean or median parameter estimates were not different between patients with and without mucositis. Mortality and overall clinical responses were similar between patients receiving oral therapy with and without mucositis. We found that isavuconazole exposures and clinical outcomes in this subset of patients with mucositis who were able to take oral isavuconazonium sulfate were comparable to those in patients without mucositis, despite the difference in oral bioavailability. Therefore, mucositis may not preclude use of the oral formulation of isavuconazonium sulfate.

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Pharmacokinetics of intravenous sildenafil in children with palliated single ventricle heart defects: effect of elevated hepatic pressures

Cardiology in the Young ◽

10.1017/s1047951115000359 ◽

2015 ◽

Vol 26 (2) ◽

pp. 354-362 ◽

Cited By ~ 8

Author(s):

Kevin D. Hill ◽

Mario R. Sampson ◽

Jennifer S. Li ◽

Robert D. Tunks ◽

Scott R. Schulman ◽

...

Keyword(s):

Drug Exposure ◽

Structural Model ◽

Single Ventricle ◽

Heart Defects ◽

Model Development ◽

Area Under The Curve ◽

Compartment Model ◽

Population Pharmacokinetic ◽

Mixed Effect ◽

The Impact

AbstractAimsSildenafil is frequently prescribed to children with single ventricle heart defects. These children have unique hepatic physiology with elevated hepatic pressures, which may alter drug pharmacokinetics. We sought to determine the impact of hepatic pressure on sildenafil pharmacokinetics in children with single ventricle heart defects.MethodsA population pharmacokinetic model was developed using data from 20 single ventricle children receiving single-dose intravenous sildenafil during cardiac catheterisation. Non-linear mixed effect modelling was used for model development, and covariate effects were evaluated based on estimated precision and clinical significance.ResultsThe analysis included a median (range) of 4 (2–5) pharmacokinetic samples per child. The final structural model was a two-compartment model for sildenafil with a one-compartment model for des-methyl-sildenafil (active metabolite), with assumed 100% sildenafil to des-methyl-sildenafil conversion. Sildenafil clearance was unaffected by hepatic pressure (clearance=0.62 L/hour/kg); however, clearance of des-methyl-sildenafil (1.94×(hepatic pressure/9)−1.33 L/hour/kg) was predicted to decrease ~7-fold as hepatic pressure increased from 4 to 18 mmHg. Predicted drug exposure was increased by ~1.5-fold in subjects with hepatic pressures ⩾10 versus <10 mmHg (median area under the curve=533 versus 792 µg*h/L).DiscussionElevated hepatic pressure delays clearance of the sildenafil metabolite – des-methyl-sildenafil – and increases drug exposure. We speculate that this results from impaired biliary clearance. Hepatic pressure should be considered when prescribing sildenafil to children. These data demonstrate the importance of pharmacokinetic assessments in patients with unique cardiovascular physiology that may affect drug metabolism.

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Is vinorelbine pharmacokinetics modified in Asian patients when compared to caucasian patients?

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e13036 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e13036-e13036

Author(s):

Pierre Ferre ◽

Zhimin Shao ◽

Zefei Jiang ◽

Dafang Zhong ◽

Chen Xiaoyan ◽

...

Keyword(s):

Clinical Studies ◽

Drug Exposure ◽

Drug Disposition ◽

Single Agent ◽

Asian Population ◽

Two Phase ◽

Asian Patients ◽

Phase Ii Studies ◽

Population Pk ◽

Caucasian Patients

e13036 Background: Pharmacokinetics (PK) of vinorelbine (VRL) has been extensively studied through a series of clinical studies, mainly conducted in Caucasian patients. Interethnic differences in drug disposition may however induce interethnic variation in drug exposure. Consequently, the PK of VRL was assessed in Asian patients during two clinical studies conducted in China, and compared to previous knowledge from non-Asian patients. Methods: Two phase II studies were conducted in China using VRL on Day 1 and 8 in combination on Day 1 with iv cisplatin for lung cancer (NSCLC) or with epirubicin for breast cancer (ABC). Patients were randomized within each study to receive either iv VRL (25 mg/m2 on cycle 1) or oral VRL. PK samples were obtained from subgroups of patients, and blood VRL and its active metabolite DVRL were quantified through LC-MS/MS. Bayesian PK parameters were calculated and VRL monotherapy results (iv 25 mg/m²; oral 60 mg/m²) were compared to historical single agent data from Caucasian patients. A population PK analysis (Variol P. et al. Eur J Clin Pharmacol, 2002: 58) was conducted to investigate for a potential effect of ethnicity. Results: VRL PK was evaluated in 38 NSCLC and 43 ABC Asian patients. Blood VRL and DVRL concentrations profiles were consistent with those from European studies. In Asian patients, mean Cltot/F (oral VRL) was 138 ± 56.5 and 179 ± 87.3 L/h for NSCLC and ABC, and mean Cltot (iv VRL) was 34.6 ± 8.82 and 41.2 ± 13.5 L/h for NSCLC and ABC. Those results did not differ from a reference European study (Bourgeois H. et al. Cancer Chemother Pharmacol, 2007: 60) (n = 48), for which mean clearance was 144 ± 66.6 and 42.8 ± 12.2 L/h for oral and iv VRL. The population PK analysis (n = 222 and 111 patients for oral and iv route) did not evidence ethnicity as a significant covariate on both clearance and oral bioavailability. Conclusions: The PK results reported from 81 Asian patients having received iv or oral monotherapy VRL treatment are consistent with previous data from European PK studies. This is in line with the metabolism knowledge of VRL, mainly involving esterase and CYP3A4 enzymes, which are not described as highly functionally polymorphic in Caucasian and Asian population.

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Evaluation of the Performance of the IMMY sona Aspergillus Galactomannan Lateral Flow Assay When Testing Serum To Aid in Diagnosis of Invasive Aspergillosis

Journal of Clinical Microbiology ◽

10.1128/jcm.00053-20 ◽

2020 ◽

Vol 58 (6) ◽

Cited By ~ 6

Author(s):

P. Lewis White ◽

Jessica S. Price ◽

Raquel Posso ◽

Morgan Cutlan-Vaughan ◽

Lorna Vale ◽

...

Keyword(s):

Invasive Aspergillosis ◽

Roc Analysis ◽

False Negative ◽

Area Under The Curve ◽

Invasive Fungal Disease ◽

Lateral Flow ◽

Optimal Threshold ◽

Serum Samples ◽

Simple Method ◽

The Impact

ABSTRACT Management of invasive aspergillosis has been improved by biomarker assays, but limited accessibility and batch testing limit the impact. Lateral flow assays (LFA) are a simple method for use outside specialist centers, provided performance is acceptable. The objective of this study was to determine the performance of the recently released IMMY sona Aspergillus LFA when testing serum samples. The study took the form of a retrospective, anonymous case/control study comprising 179 serum samples from 136 patients with invasive fungal disease, previously documented using recently revised internationally accepted definitions. The LFA was performed following the manufacturer’s instructions using a cube reader to generate a galactomannan index (GMI). Performance parameters were determined, and receiver operator characteristic (ROC) analysis was used to identify an optimal threshold. Concordance with the Bio-Rad Aspergillus Ag assay (GM-EIA) was performed. At the recommended positivity threshold (GMI ≥ 0.5), LFA sensitivity and specificity were 96.9% (31/32) and 98% (98/100), respectively. ROC analysis confirmed the optimal threshold and generated an area under the curve of 0.9919. Qualitative agreement between LFA and GM-EIA was 89.0%, generating a Kappa statistic of 0.698, representing good agreement, with most discordance arising due to false-negative GM-EIA samples that were positive by LFA. The median GMI generated by the LFA was significantly greater than that generated by the GM-EIA. The IMMY sona Aspergillus LFA, when used with a cube reader, provides a rapid alternative to the well-established GM-EIA, potentially detecting more GM epitopes and enhancing sensitivity.

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P332 Population pharmacokinetics of ozanimod and active metabolite CC112273 in patients with ulcerative colitis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.456 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S355-S357

Author(s):

J Shen ◽

D Tatosian ◽

L Sid-Otmane ◽

N Teuscher ◽

L Chen ◽

...

Keyword(s):

Ulcerative Colitis ◽

Body Weight ◽

Drug Exposure ◽

Smoking Status ◽

Plasma Concentrations ◽

Hepatic Function ◽

Population Pk ◽

Apparent Clearance ◽

Post Hoc ◽

The Impact

Abstract Background Ozanimod is an oral small molecule sphingosine 1-phosphate receptor modulator approved for relapsing forms of multiple sclerosis (RMS) and under development for ulcerative colitis (UC) and Crohn’s disease (CD). Following multiple dosing of ozanimod in healthy subjects, ozanimod and two of the active metabolites CC112273 and CC1084037 represent approximately 6%, 73%, and 15% of circulating total active drug exposure, respectively. Two separate pharmacokinetic (PK) models were developed for the most prominent metabolite CC112273 and ozanimod. CC1084037 was not modeled due to the high correlation between CC112273 and CC1084037 plasma concentrations. Therefore, this analysis aims to characterise the PK of ozanimod and the major metabolite CC112273 in UC and RMS population. Methods Subjects from 11 studies (Phase 1 to Phase 3) in healthy volunteers, RMS, and UC patients were included in this population PK analysis. The analyses included a total of 18901 concentrations from 2890 subjects for CC112273 and 18834 PK concentrations from 2977 subjects for ozanimod. A 2-compartment model was used to describe the concentration-time profiles of both ozanimod and CC112273, separately. The influence of weight, age, sex, race, disease, or smoking status and hepatic function on the PK of ozanimod and CC112273 were explored. The impact of concomitant corticosteroids on CC112273 PK were evaluated post hoc. Results While the overall apparent clearance of ozanimod was 7% lower in RMS patients compared to UC, similar exposures were observed in both populations. The most influential covariate on ozanimod PK was body weight, with a modest 23% increase in apparent clearance for a 102-kg subject relative to a 70-kg subject (Figure 1). The apparent clearance of CC112273 was 16% greater in RMS patients compared to UC patients, resulting in a slightly higher exposure for UC patients. Increasing body weight had a modest reduction in clearance, while smoking had the largest influence on CC112273 PK of approximately 108% increased clearance (Figure 2). Post-hoc results showed no impact of concomitant prednisone or prednisolone on the PK of CC112273. Other factors, including age, race, sex, or hepatic impairment did not impact the PK of ozanimod or CC112273 PK. Conclusion The population PK model of CC112273 indicates that covariates with the largest effect on CC112273 PK parameters were body weight and smoking status. However, no covariate impacted clearance by more than 25%. The PK of ozanimod and CC112273 were not meaningfully impacted by age including in the elderly, body weight, race, sex, hepatic function, or concomitant prednisone or prednisolone. Overall, the PK of ozanimod and CC112273 were comparable in UC and RMS patients.

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1090. Does calculation method matter for targeting vancomycin AUC?

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1284 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S636-S636

Author(s):

Jack Chang ◽

Dhara Patel ◽

Kimberly C Claeys ◽

Marc H Scheetz ◽

Emily Heil

Keyword(s):

Bayesian Model ◽

Bayesian Method ◽

Drug Exposure ◽

Area Under The Curve ◽

First Order ◽

Bayesian Estimates ◽

Actual Patient ◽

Spearman's Rho ◽

Spearman’S Rho ◽

Population Pk

Abstract Background Recent vancomycin (VAN) guidelines recommend targeting an area under the curve (AUC) concentration of 400-600 for treatment of methicillin resistant Staphylococcus aureus infections. Multiple strategies for calculating AUC exist, including first order pharmacokinetic (foPK) equations and Bayesian models. Most clinical applications of foPK assume unchanged patient status and project ideal administration times to estimate exposure. Bayesian modeling provides the best estimate of true drug exposure and can incorporate changing patient covariates and exact doses. We compared two commonly used foPK methods to Bayesian estimates of VAN AUC. Graphs depict calculated AUCs using the three different methods: 1) Population PK estimated (foPOPPK) 2) Two-level first dose estimated (foFDPK) 3) Bayesian estimated. Methods First order equations were performed using population PK estimates (foPOPPK) to estimate steady state (SS) AUC and initial doses. Two concentrations after first dose were used to estimate SS AUC (foFDPK). A 2-compartment Bayesian model allometrically scaled for weight and adjusted for creatinine clearance was used to determine 24-48 hour AUCs. Differences between AUCs were compared using a mixed-effects analysis, and correlation of foPK equations to Bayesian estimates was described using Spearman’s correlation. Patient results from each method were classified as below (< 400), within (400-600), or above ( >600) targets. Results 65 adult patients were included. The median and IQR for calculated AUCs using foPOPPK, foFDPK, and Bayesian methods were 495.6 (IQR: 76.6), 498.2 (IQR: 107.4), and 472.1 (IQR: 177.9), respectively with p >0.65 for both foPK methods vs. the Bayesian method. AUCs predicted by foPK equations were poorly correlated with Bayesian AUCs (Spearman’s rho= -0.08, p=0.55), while AUCs from foFDPK better correlated with Bayesian AUCs (Spearman’s rho= 0.48, p=0.00). AUCs were within, above, and below target for 54%, 20%, and 26% for the Bayesian model; 95%, 5% and 0% for foPOPPK; and 74%, 12%, and 14% for foFDPK. foPK AUC estimates concurred with Bayesian estimates only 52% of the time. Conclusion AUCs calculated by the three methods did not differ on average, but dosing recommendations for foPK at the patient level varied substantially compared to the Bayesian method. This difference is because Bayesian estimation incorporates actual patient exposures while foPK equations rely on idealized dose timing to predict AUCs. Disclosures Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau) Marc H. Scheetz, PharmD, MSc, Nevakar (Grant/Research Support)SuperTrans Medical (Consultant)US Patent #10688195B2 (Other Financial or Material Support, Patent holder)

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637. Outcomes by Body Mass Index (BMI) in the STRIVE Phase 2 Trial of Once-Weekly Rezafungin for Treatment of Candidemia and Invasive Candidiasis Compared with Caspofungin

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.831 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S378-S379

Author(s):

Jose A Vazquez ◽

Shawn Flanagan ◽

Peter Pappas ◽

George R Thompson ◽

Taylor Sandison ◽

...

Keyword(s):

Invasive Candidiasis ◽

Drug Exposure ◽

Clinical Signs ◽

Area Under The Curve ◽

Panel Member ◽

Invasive Fungal Disease ◽

Invasive Disease ◽

Marrow Transplant ◽

Important Variable ◽

Phase 2

Abstract Background There is increasing evidence of antifungal underdosing in the treatment of invasive disease, particularly in special populations such as the obese. Body size is often an important variable affecting drug exposure, and pharmacokinetic (PK) models of antifungal dosing have suggested size-based dose adjustments to achieve target drug exposure. Rezafungin (RZF) is a novel echinocandin in Phase 3 development for treatment of candidemia and invasive candidiasis (IC) and for prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis in blood and marrow transplant recipients. Distinctive PK properties of RZF (e.g., long half-life, extensive tissue distribution, and front-loaded drug exposure) lend themselves to RZF once-weekly (QWk) dosing and antifungal efficacy. In this sub-analysis of the Phase 2 STRIVE trial of RZF in the treatment of candidemia and/or IC, outcomes based on patient BMI were evaluated. Methods The STRIVE trial (NCT02734862) compared the safety and efficacy of RZF QWk compared with once-daily caspofungin (Fig. 1). For this subanalysis, data were stratified by BMI categories of < 30 kg/m2 and ≥ 30 kg/m2. Efficacy (overall response [resolution of clinical signs of infection + mycological eradication], mycological response, and investigator assessment of clinical response) and safety (treatment-emergent adverse events [TEAEs]) endpoints by treatment group were evaluated, as well as PK data (area under the curve [AUC]) from RZF-treated patients. Figure 1. Results Mean BMI values were similar across treatment arms (26.9 kg/m2 in RZF Group 1 and 26.8 kg/m2 in RZF Group 2 and CAS arms). Efficacy outcomes at Day 14 were similar between BMI categories (Table 1). Rates of TEAEs were generally similar between BMI categories as well (Table 2), with no concerning safety trends. Following one dose of RZF 400 mg (Week 1), the ranges of AUCs by BMI category overlapped and there was a minor mean difference of ~20% (lower for those with BMI ≥ 30 kg/m2) (Fig. 2). Table 1 Table 2 Figure 2. Conclusion The safety, efficacy, and PK of RZF in the Phase 2 STRIVE trial was consistent across BMI categories. These results suggest that dose adjustments in obese patients are not necessary. These findings contribute to the evaluation of RZF in a range of patient populations and its ongoing development. Disclosures Shawn Flanagan, PhD, Cidara Therapeutics, Inc. (Employee, Shareholder) Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Taylor Sandison, MD, MPH, Cidara Therapeutics, Inc. (Employee, Shareholder) Patrick M. Honore, MD, PhD, FCCM, Cidara Therapeutics, Inc. (Scientific Research Study Investigator)

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Genetic Variation: Impact on Folate (and Choline) Bioefficacy

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000040 ◽

2010 ◽

Vol 80 (45) ◽

pp. 319-329 ◽

Cited By ~ 9

Author(s):

Allyson A. West ◽

Marie A. Caudill

Keyword(s):

Carbon Metabolism ◽

Genetic Variants ◽

Plasma Homocysteine ◽

Water Soluble ◽

Gene Interactions ◽

Dietary Folate ◽

Methyl Donors ◽

Common Genetic Variants ◽

One Carbon Metabolism ◽

The Impact

Folate and choline are water-soluble micronutrients that serve as methyl donors in the conversion of homocysteine to methionine. Inadequacy of these nutrients can disturb one-carbon metabolism as evidenced by alterations in circulating folate and/or plasma homocysteine. Among common genetic variants that reside in genes regulating folate absorptive and metabolic processes, homozygosity for the MTHFR 677C > T variant has consistently been shown to have robust effects on status markers. This paper will review the impact of genetic variants in folate-metabolizing genes on folate and choline bioefficacy. Nutrient-gene and gene-gene interactions will be considered along with the need to account for these genetic variants when updating dietary folate and choline recommendations.

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The Impact of Missing and Error-Prone Auxiliary Information on Sparse-Matrix Sub-Population Parameter Estimates

Methodology ◽

10.1027/1614-2241/a000095 ◽

2015 ◽

Vol 11 (3) ◽

pp. 89-99 ◽

Cited By ~ 1

Author(s):

Leslie Rutkowski ◽

Yan Zhou

Keyword(s):

Sparse Matrix ◽

Small Body ◽

Auxiliary Information ◽

Poor Quality ◽

Quality Data ◽

Estimation Methods ◽

Parameter Estimates ◽

Population Parameter ◽

Conditioning Model ◽

The Impact

Abstract. Given a consistent interest in comparing achievement across sub-populations in international assessments such as TIMSS, PIRLS, and PISA, it is critical that sub-population achievement is estimated reliably and with sufficient precision. As such, we systematically examine the limitations to current estimation methods used by these programs. Using a simulation study along with empirical results from the 2007 cycle of TIMSS, we show that a combination of missing and misclassified data in the conditioning model induces biases in sub-population achievement estimates, the magnitude and degree to which can be readily explained by data quality. Importantly, estimated biases in sub-population achievement are limited to the conditioning variable with poor-quality data while other sub-population achievement estimates are unaffected. Findings are generally in line with theory on missing and error-prone covariates. The current research adds to a small body of literature that has noted some of the limitations to sub-population estimation.

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Bleeding Classification in Clinical Trials: Observer Variability and Clinical Relevance

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657713 ◽

1997 ◽

Vol 78 (04) ◽

pp. 1189-1192 ◽

Cited By ~ 22

Author(s):

Yvonne P Graafsma ◽

Martin H Prins ◽

Anthonie W A Lensing ◽

Rob J de Haan ◽

Menno V Huisman ◽

...

Keyword(s):

Major Bleeding ◽

Clinical Relevance ◽

Area Under The Curve ◽

Weighted Kappa ◽

Clinical Severity ◽

Minor Bleeding ◽

Recent Trial ◽

Bleeding Episodes ◽

The Impact ◽

Adjudication Committee

SummaryTo evaluate the bleeding classification in a recent trial on venous thrombosis treatment, a selection of reported bleeding episodes was adjudicated twice by an independent committee and graded by the treating physician and independent clinical experts on the clinical severity and impact on the patient’s life.The kappa values for the dichotomy major bleeding versus minor or no bleeding were 0.79 (95% CI, 0.57-1.0) for the agreement between the two members of the adjudication committee and 0.77 (95% CI, 0.52-1.0) for the agreement between both adjudication sessions. The kappa values for the dichotomy major or minor bleeding versus no bleeding were 0.42 and 0.44. The weighted kappa values for the agreement between the treating physician and the independent experts were 0.76 for the Clinical severity and 0.79 for the impact on the patient’s life (95% CI, 0.63-0.88 and 0.70-0.89). The association between the adjudication result expressed as major bleeding or minor or no bleeding and the Clinical grading by the treating physician resulted in an ROC curve with an area under the curve of 0.98 for the Clinical severity and 0.99 for the impact on the patient’s life. The dichotomy major or minor bleeding versus no bleeding resulted in areas under the curve of 0.70 and 0.66.In conCIusion, the applied criteria for major bleeding are reproducible and Clinically relevant. The criteria for minor bleeding are not reproducible and are less associated with the observed Clinical relevance.

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Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2020.13.5.7 ◽

2020 ◽

Vol 13 (5) ◽

pp. 5102-5109

Author(s):

Venu Madhav K ◽

Somnath De ◽

Chandra Shekar Bonagiri ◽

Sridhar Babu Gummadi

Keyword(s):

Oral Bioavailability ◽

Oral Delivery ◽

Solid Dispersions ◽

In Vitro Release ◽

Aqueous Solubility ◽

Water Soluble ◽

Scanning Calorimetry ◽

In Vivo Evaluation

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension. From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.

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