Design and stability of pediatric oral formulation of imatinib

2021 ◽  
pp. 107815522199120
Author(s):  
Mélanie Hinterlang ◽  
Amandine Gendron ◽  
Thomas Fleury ◽  
André Rieutord ◽  
Anastasia Vrana ◽  
...  
Keyword(s):  
High Performance ◽  
Protein Tyrosine Kinase ◽  
Pediatric Patients ◽  
Kinase Inhibitor ◽  
Philadelphia Chromosome ◽  
Oral Solution ◽  
Stability Study ◽  
Uv Detector ◽  
Stability Parameters ◽  
Tablet Dosage

Background Imatinib is a protein-tyrosine kinase inhibitor which is currently only commercially available as a tablet dosage form in the strength of 100mg and 400mg. The elaboration of new oral liquid formulations is suitable in pediatrics and for patients who have difficulties to swallow, notably in the absence of commercial forms. This enables the adaptation of dosage and secure the administration. Objectives The formulation of an oral pediatric solution of imatinib at a concentration of 30 mg/mL and the evaluation of its stability for the treatment of pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia. Methods The physicochemical stability parameters: appearance, pH, osmolality, and drug content of formulation were evaluated for 30 days when stored at 2–8°C. Concentration of solution was measured with a validated method using high performance liquid chromatography (HPLC) coupled with an absorbance UV detector. Equally, microbiological stability was performed. Results The remaining imatinib concentration was at least 95% of the initial concentration after 30 days stored in fridge temperature. No changes were observed regarding the physical properties of the formulation during the study period. Conclusions The stability study showed that the imatinib oral solution at a concentration of 30 mg/mL provides an alternative option at the commercial tablet dosage forms for pediatric patients and patients who have difficulties to swallow.

ICH/FDA Guidelines-Compliant Validated Stability-Indicating HPLC-UV Method for the Determination of Axitinib in Bulk and Dosage Forms

2020 ◽  
Vol 16 (8) ◽  
pp. 1106-1112
Author(s):  
Ibrahim A. Darwish ◽  
Nasr Y. Khalil ◽  
Mohammad AlZeer
Keyword(s):  
High Performance ◽  
Kinase Inhibitor ◽  
Degradation Products ◽  
Internal Standard ◽  
Dosage Forms ◽  
Uv Detector ◽  
Stability Indicating ◽  
Therapeutic Benefits ◽  
Relative Standard

Background: Axitinib (AXT) is a member of the new generation of the kinase inhibitor indicated for the treatment of advanced renal cell carcinoma. Its therapeutic benefits depend on assuring the good-quality of its dosage forms in terms of content and stability of the pharmaceutically active ingredient. Objective: This study was devoted to the development of a simple, sensitive and accurate stabilityindicating high-performance liquid chromatographic method with ultraviolet detection (HPLC-UV) for the determination of AXT in its bulk and dosage forms. Methods: Waters HPLC system was used. The chromatographic separation of AXT, internal standard (olaparib), and degradation products were performed on the Nucleosil CN column (250 × 4.6 mm, 5 μm). The mobile phase consisted of water:acetonitrile:methanol (40:40:20, v/v/v) with a flow rate of 1 ml/min, and the UV detector was set at 225 nm. AXT was subjected to different accelerated stress conditions and the degradation products, when any, were completely resolved from the intact AXT. Results: The method was linear (r = 0.9998) in the concentration range of 5-50 μg/ml. The limits of detection and quantitation were 0.85 and 2.57 μg/ml, respectively. The accuracy of the method, measured as recovery, was in the range of 98.0-103.6% with relative standard deviations in the range of 0.06-3.43%. The results of stability testing revealed that AXT was mostly stable in neutral and oxidative conditions; however, it was unstable in alkaline and acidic conditions. The kinetics of degradation were studied, and the kinetic rate constants were determined. The proposed method was successfully applied for the determination of AXT in bulk drug and dosage forms. Conclusions: A stability-indicating HPLC-UV method was developed and validated for assessing AXT stability in its bulk and dosage forms. The method met the regulatory requirements of the International Conference on Harmonization (ICH) and the Food and Drug Administration (FDA). The results demonstrated that the method would have great value when applied in quality control and stability studies for AXT.

FORCED DEGRADATION STUDIES OF OLMESARTAN MEDOXOMIL AND CHLORTHALIDONE: DEVELOPMENT AND VALIDATION OF STABILITY-INDICATING RP‑HPLC METHOD

INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (03) ◽  
pp. 39-45
Author(s):  
A Sherje ◽  
A. Sonalkar ◽  
Keyword(s):  
High Performance ◽  
Dosage Form ◽  
Olmesartan Medoxomil ◽  
The United States ◽  
High Performance Liquid Chromatographic ◽  
Reversed Phase ◽  
Hplc Method ◽  
Forced Degradation ◽  
Uv Detector ◽  
Tablet Dosage

A reversed-phase high-performance liquid chromatographic method was developed for the simultaneous determination of olmesartan medoxomil (OLME) and chlorthalidone (CHLOR) in tablet dosage form. The analysis was performed on Inertsil ODS C18 (250 x 4.6 mm, 5 μ) using KH2PO4 phosphate buffer (pH) and acetonitrile as mobile phase in the proportion of 60: 40 v/v at flow rate of 1.0 mL/min. Detection of drugs was carried out in isocratic mode using UV detector at 275 nm. The retention time of OLME and CHLOR was 13.9 ± 0.1 min. and 4.4 ± 0.5 min., respectively and the total run time was 20 min. The method was validated according to the requirements of the United States Pharmacopeia. The percentage recoveries was found to be in the range of 98.9 - 100.7%. The method was successfully applied to the assay of OLME and CHLOR in tablet dosage form.

Design and stability study of an oral solution of amlodipine besylate for pediatric patients

2016 ◽  
Vol 92 ◽  
pp. 220-223 ◽  
Author(s):  
A.C. van der Vossen ◽  
I. van der Velde ◽  
O.S.N.M. Smeets ◽  
D.J. Postma ◽  
A. Vermes ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Oral Solution ◽  
Stability Study ◽  
Amlodipine Besylate

Studies on the Quantification of Mutation Resistance to Specific Drug Therapy in Chronic Myeloid Leukemia patients

2021 ◽  
pp. 4092-4100
Author(s):  
Ankit Darji ◽  
Praful Bharadia
Keyword(s):  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Protein Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Philadelphia Chromosome ◽  
Newly Diagnosed ◽  
Rt Pcr ◽  
Abl Tyrosine Kinase ◽  
Pcr Method ◽  
Complete Haematological Response

Imatinib is a type of protein tyrosine kinase inhibitor which inhibits the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome i.e. the BCR-ABL tyrosine kinase, abnormality in CML patient. The aim of the study is to assess the response of imatinib in CML patients and to observe resistance to imatinib. Study was performed at Ahmedabad, Gujarat, India. Dose of 400, 600, 800 mg of Imatinib was found to be prescribed to all patients during the study. Comparison of laboratory parameters and PCR data were done after measurement by RT-PCR method. Total 256 patients with CML were enrolled in the study. 196 patients had completed study as per protocol. 38 patients were newly diagnosed whereas 158 patients were already diagnosed with CML. 89.29% (n = 175) of patients achieved complete haematological response, Complete MolR were achieved in n = 41 at 6th months, n = 1 at 12th month and 18th month and no patient was found with none CyR out of 196 patients; no patient were found with minimal CyR at 6th month, 2 patient were at 12th month and 3 patients were at 18th month. Mean PCR value (BCR-ABL/ABL ratio) in patient was found 0.245±1.16 at Day 0, 0.824±1.51 at 6th month, 4.086±9.58 at 12th month and 6.713±11.32 at 18th month visit. In conclusion, it was observed that resistance to imatinib might be developed within an average time of 12 months in the patients due to which survival rate was drastically reduced.

scholarly journals HIGH PERFORMANCE LIQUID CHROMATOGRAPHY METHOD VALIDATION OF α-MANGOSTIN ASSAY IN MANGOSTEEN (Garcinia mangostana L.) FRUIT RIND EXTRACT FORMULATED IN ORAL SOLUTION

2016 ◽  
Vol 11 (1) ◽  
pp. 38
Author(s):  
Liliek Nurhidayati ◽  
Siti Sofiah ◽  
Ros Sumarny ◽  
Kevin Caesar
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Oral Solution ◽  
Assay Method ◽  
Uv Detector ◽  
Garcinia Mangostana ◽  
Chromatography Method ◽  
Relative Standard ◽  
Fruit Rind

<p>Mangosteen fruit rind extract contain a lot of antioxidants. α-Mangostin is a component in mangosteen fruit rind that has highest antioxidant effect. The oral solution containing mangosteen fruit rind extract is required an assay method for quality assessment. Determination of a very low concentration of analyte in sample with very complex matrix, such as α-mangostin in oral solution, needs a selective and sensitive method, such as high performance liquid chromatography (HPLC). In this study, α-mangostin assay was performed by reverse phase HPLC system using octadecylsilane (C18) as stationary phase,  methanol-water (90:10) as mobile phase, the flow rate is 1.0 mL/min, and the UV detector at 316 nm. The retention time of α-mangostin was 9.622 minutes. Peak of α-mangostin was well separated with resolution of 1.725. Linearity was in the range of 1.67-5.01 ppm with correlation coefficient of 0.9986. The relative standard deviation (RSD) was 1.30 %, the recovery was in the range of 95.80-100.76 </p>

scholarly journals Determination of Rosuvastatin and Ezetimibe in a Combined Tablet Dosage Form Using High-Performance Column Liquid Chromatography and High-Performance Thin-Layer Chromatography

2010 ◽  
Vol 93 (4) ◽  
pp. 1222-1227 ◽  
Author(s):  
Susheel John Varghese ◽  
Thengungal Kochupappy Ravi
Keyword(s):  
Simultaneous Determination ◽  
Mobile Phase ◽  
High Performance ◽  
Dosage Form ◽  
Good Precision ◽  
Uv Detector ◽  
Solution Ph ◽  
Phase Quantification ◽  
Tablet Dosage

Abstract This paper describes validated HPLC and HPTLC methods for the simultaneous determination of rosuvastatin (ROS) and ezetimibe (EZE) in a combined tablet dosage form. The isocratic RP-HPLC analysis was performed on a Chromolith C18 column (100 6 mm id) using 0.1 (v/v) orthophosphoric acid solution (pH 3.5)acetonitrile (63 + 37, v/v) mobile phase at a flow rate of 1 mL/min at ambient temperature. Quantification was carried out using a photodiode array UV detector at 245 nm over the concentration range of 0.510 g/mL for ROS and EZE. The HPTLC separation was carried out on an aluminum-backed sheet of silica gel 60F254 layers using n-butyl acetatechloroformglacial acetic acid (1 + 8 + 1, v/v/v) mobile phase. Quantification was achieved with UV densitometry at 245 nm over a concentration range of 0.10.9 g/spot for ROS and EZE. The analytical methods were validated according to International Conference on Harmonization guidelines. Low RSD values indicated good precision. Both methods were successfully applied for the analysis of the drugs in laboratory-prepared mixtures and commercial tablets. No chromatographic interference from the tablet excipients was found. These methods are simple, precise, and sensitive, and are applicable for simultaneous determination of ROS and EZE in pure powder and tablets.

HIGH PERFORMANCE LIQUID CHROMATOGRAPHY METHOD VALIDATION OF α-MANGOSTIN ASSAY IN MANGOSTEEN (Garcinia mangostana L.) FRUIT RIND EXTRACT FORMULATED IN ORAL SOLUTION

2015 ◽  
Vol 11 (1) ◽  
pp. 38
Author(s):  
Liliek Nurhidayati ◽  
Siti Sofiah ◽  
Ros Sumarny ◽  
Kevin Caesar
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Oral Solution ◽  
Assay Method ◽  
Uv Detector ◽  
Garcinia Mangostana ◽  
Chromatography Method ◽  
Relative Standard ◽  
Fruit Rind

<p>Mangosteen fruit rind extract contain a lot of antioxidants. α-Mangostin is a component in mangosteen fruit rind that has highest antioxidant effect. The oral solution containing mangosteen fruit rind extract is required an assay method for quality assessment. Determination of a very low concentration of analyte in sample with very complex matrix, such as α-mangostin in oral solution, needs a selective and sensitive method, such as high performance liquid chromatography (HPLC). In this study, α-mangostin assay was performed by reverse phase HPLC system using octadecylsilane (C18) as stationary phase,  methanol-water (90:10) as mobile phase, the flow rate is 1.0 mL/min, and the UV detector at 316 nm. The retention time of α-mangostin was 9.622 minutes. Peak of α-mangostin was well separated with resolution of 1.725. Linearity was in the range of 1.67-5.01 ppm with correlation coefficient of 0.9986. The relative standard deviation (RSD) was 1.30 %, the recovery was in the range of 95.80-100.76 </p>

scholarly journals Development and validation of RP-HPLC and UV method for erlotinib hydrochloride tablets

2021 ◽  
Vol 6 (3) ◽  
pp. 144-151
Author(s):  
R Vijay Amirtharaj ◽  
S Lavanya
Keyword(s):  
High Performance ◽  
Potassium Dihydrogen Phosphate ◽  
High Performance Liquid Chromatographic ◽  
Hplc Method ◽  
Dihydrogen Phosphate ◽  
Uv Detector ◽  
Column Temperature ◽  
Development And Validation ◽  
Tablet Dosage ◽  
Liquid Chromatographic

A simple, sensitive, precise, selective reverse phase high performance liquid chromatographic method was developed and validated for erlotinib hydrochloride in tablet dosage form.(0.02M)The separation was achieved on C18 column (150mm×4.6mm.i.d.,5.0μm) using potassium dihydrogen phosphate: acetonitrile in the ratio 50:50v/v as mobile phase having pH 4.5 was adjusted with methanol and flow rate 1ml/min. Detection was carried out using a UV detector at 248nm. The column temperature was adjusted at 30ᵒC. The method was validated for precision, linearity and range, stability and robustness. The developed and validated method was successfully applied for the quantitative analysis of ERLONAT tablets. The total chromatographic analysis time per sample was about 7min with Erlotinib eluting at 6.547min.Validation studies demonstrated that this HPLC method is simple, specific, rapid, reliable and reproducible. The standard curves were linear over the concentration ranges, 88.32- 132.48μg/ml for erlotinib. The high recovery confirms the suitability of the proposed method for the determination of Erlotinib in ERLONAT tablets. The results of analysis have been validated according to ICH guideline requirements. The method can be applied for Erlotinib hydrochloride tablets.

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