scholarly journals A Comprehensive Approach to Compatibility Testing Using Chromatographic, Thermal and Spectroscopic Techniques: Evaluation of Potential for a Monolayer Fixed-Dose Combination of 6-Mercaptopurine and Folic Acid

2021 ◽  
Vol 14 (3) ◽  
pp. 274
Author(s):  
Edvin Brusač ◽  
Mario-Livio Jeličić ◽  
Matija Cvetnić ◽  
Daniela Amidžić Klarić ◽  
Biljana Nigović ◽  
...  
Keyword(s):  
Folic Acid ◽  
Development Strategy ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Forced Degradation ◽  
Spectroscopic Techniques ◽  
Scanning Calorimetry ◽  
Forced Degradation Studies ◽  
Dose Combination ◽  
Inflammatory Bowel

In this work, a systematical compatibility investigation of 6-mercaptopurine and folic acid, two commonly used medications in the treatment of inflammatory bowel disease, for the needs of a fixed-dose combination development strategy is shown. Various techniques and approaches, such as differential scanning calorimetry, isothermal stress testing, attenuated total reflectance–Fourier-transform infrared spectroscopy, dissolution medium stability and forced degradation studies, were used to elucidate the possible interactions from different aspects. The results predominantly point to the absence of physicochemical interactions between the examined substances in a variety of possible conditions. However, the forced degradation of the blend of substances and excipients in basic conditions showed a drastic degradation of 6-mercaptopurine, signifying that attention needs to be directed to the careful selection of the excipients for the formulation. To sum up, our findings indicate that a fixed-dose combination of 6-mercaptopurine and folic acid could be produced using one formulation blend, immensely simplifying its manufacture.

scholarly journals Drug–Drug Compatibility Evaluation of Sulfasalazine and Folic Acid for Fixed-Dose Combination Development Using Various Analytical Tools

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 400
Author(s):  
Mario-Livio Jeličić ◽  
Edvin Brusač ◽  
Stanislav Kurajica ◽  
Matija Cvetnić ◽  
Daniela Amidžić Amidžić Klarić ◽  
...  
Keyword(s):  
Folic Acid ◽  
Principal Component ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Forced Degradation ◽  
Chemical Compatibility ◽  
Dose Combination ◽  
Multiple Drugs ◽  
Analytical Tools ◽  
Insight Into

The simultaneous administration of sulfasalazine and folic acid is regular practice in the therapy of inflammatory bowel diseases in order to maintain sufficient folate concentration in patients. Having multiple drugs in the therapy increases the possibility of patients failing adherence, thus unintentionally endangering their health. A fixed-dose combination of sulfasalazine and folic would simplify the classical polytherapeutic approach; however, the physicochemical compatibility investigation of two active pharmaceutical ingredients plays an important role in the development of such a product. In this work, various analytical tools were used to determine the physicochemical compatibility of sulfasalazine and folic acid. For the evaluation of chemical compatibility, infrared spectroscopy in combination with advanced statistical methods, such as the principal component analysis and cluster analysis, were used, whilst a simultaneous thermogravimetry/differential thermal analysis gave us an insight into the physical compatibility of two drugs. Isothermal stress testing, forced degradation and dissolution studies, followed by the analysis with a developed chromatographic method for the monitoring of folic acid, sulfasalazine and two of its related impurities, sulfapyridine and salicylic acid, gave us an insight into its chemical compatibility. The combination of the results obtained from the used techniques implies a satisfactory physicochemical compatibility between sulfasalazine and folic acid, which opens the path to the development of the proposed fixed-dose combination.

scholarly journals Physicochemical Compatibility Investigation of Mesalazine and Folic Acid Using Chromatographic and Thermoanalytical Techniques

2020 ◽  
Vol 13 (8) ◽  
pp. 187
Author(s):  
Mario-Livio Jeličić ◽  
Edvin Brusač ◽  
Daniela Amidžić Klarić ◽  
Biljana Nigović ◽  
Sabina Keser ◽  
...  
Keyword(s):  
Folic Acid ◽  
Inflammatory Bowel Diseases ◽  
Hplc Method ◽  
Fixed Dose ◽  
Forced Degradation ◽  
Physicochemical Interaction ◽  
Scanning Calorimetry ◽  
Vitamin B9 ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel disease is a common name for Crohn’s disease and ulcerative colitis. These inflammatory states cause damage in the sidewalls of the gastrointestinal tract, resulting in malabsorption of food and vitamins. Folic acid (Vitamin B9) is often associated with inflammatory bowel diseases since reduced overall folate concentration in the human body may lead to the development of colorectal cancer and megaloblastic anaemia. However, its deficiency is easily compensated by taking an additional folic acid pill during regular therapy. At the moment, there are no studies that have examined the compatibility of folic acid with 5-aminosalicylate drugs used in the treatment of inflammatory bowel diseases. In this work, differential scanning calorimetry, forced degradation studies, isothermal stress testing and dissolution stability testing were used to determine the stability of folic acid and one of the most commonly used 5-aminosalicylates, mesalazine, when present in the same solution or blend. To monitor the assay of folic acid, mesalazine and nine of its related impurities, a single HPLC method was developed. Results of compatibility studies showed that no physicochemical interaction between mesalazine and folic acid occurs when combined, opening the path to the development of new formulations, such as a mesalazine/folic acid fixed-dose combination.

scholarly journals Isolation, Identification and Characterization of Degradation Impurity of Atorvastatin in Fixed Dose Combination of Atorvastatin and Ezetimibe

2019 ◽  
Vol 11 (05) ◽  
Author(s):  
Rajesh Desai ◽  
Suresh Koradia
Keyword(s):  
Reversed Phase ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Forced Degradation ◽  
Preparative Hplc ◽  
Atorvastatin Calcium ◽  
Isolation And Characterization ◽  
Dose Combination ◽  
Liquid Chromatographic

The objective of this study is to isolation and characterization of unknown degradation product of Atorvastatin calcium in combination formulation product with Ezetimibe by using modern techniques of separation and aracterization. An unknown impurity is generating during a forced degradation study of Atorvastatin and Ezetimibe fixed-dose combination tablets. By using the gradient reversed-phase high-pressure liquid chromatographic method, unknown degradation impurity was detected and quantified in the range of 0.05% to 0.2% of Atorvastatin. The impurity was enriched by extreme oxidation degradation of Atorvastatin and isolated through preparative HPLC. The structure of the impurity was characterized by mass and NMR spectrum.

scholarly journals COMPATIBILITY STUDY BETWEEN PRAVASTATIN AND EZETIMIBE, AND PHARMACEUTICAL EXCIPIENTS USED IN FIXED-DOSE COMBINATION TABLET

2021 ◽  
pp. 84-89
Author(s):  
KANG MIN KIM
Keyword(s):  
High Performance ◽  
Physical Stability ◽  
Drug Formulation ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Compatibility Study ◽  
Scanning Calorimetry ◽  
Combination Tablet ◽  
Tg Analysis ◽  
Dose Combination

Objective: The purpose of this study was to qualitatively predict drug-excipient binding interactions for stable drug formulation of a pravastatin and ezetimibe fixed-dose combination (FDC) tablet. Methods: Drug impurity-excipient interactions under accelerated conditions (40°C/75% relative humidity) for 4 weeks were confirmed by high-performance liquid chromatography, X-ray diffraction (XRD), differential scanning calorimetry (DSC) and thermogravimetric (TG) analysis. Results: Pravastatin impurity was affected by four excipients under accelerated conditions for 4 weeks. Ezetimibe was affected by two excipients. Any other results were within the acceptance criteria. XRD analysis for physical stability revealed characteristic peaks of pravastatin and ezetimibe at a diffraction angle of 2θ (pravastatin: 4.1–24.4°, and ezetimibe: 13.62–29.59°) without a change in the crystalline form after 4 weeks. DSC and TG analysis showed evidence of stability in Alu-Alu foil. Conclusion: Thus, the tested excipients were confirmed to be compatible with pravastatin and ezetimibe and can be used in FDC bi-layer tablets.

Development of a HPLC-DAD stability-indicating method and compatibility study of azathioprine and folic acid as a prerequisite for a monolayer fixed-dose combination

2021 ◽  
Vol 13 (11) ◽  
pp. 1422-1431
Author(s):  
Edvin Brusač ◽  
Mario-Livio Jeličić ◽  
Daniela Amidžić Klarić ◽  
Biljana Nigović ◽  
Sabina Keser ◽  
...  
Keyword(s):  
Folic Acid ◽  
Process Control ◽  
Quality Assessment ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Compatibility Study ◽  
Stability Indicating ◽  
Stability Indicating Method ◽  
Dose Combination ◽  
Active Substances

Physicochemical compatibility of active substances confirmed using multiple techniques and a stability-indicating method developed for quality assessment and in-process control.

APPLICATION OF EXPERIMENTAL DESIGNS FOR OPTIMIZATION OF FORCED DEGRADATION STUDIES AND DEVELOPMENT OF STABILITY-INDICATING HPTLC METHOD FOR COMBINATION OF CEFPODOXIME PROXETIL AND OFLOXACIN

INDIAN DRUGS ◽  
2018 ◽  
Vol 55 (07) ◽  
pp. 49-58
Author(s):  
V. T Gawande ◽  
K. G Bothara
Keyword(s):  
Fixed Dose ◽  
Forced Degradation ◽  
Cefpodoxime Proxetil ◽  
Stability Indicating ◽  
Ich Guidelines ◽  
Tlc Plates ◽  
Forced Degradation Studies ◽  
Dose Combination ◽  
Degradation Studies ◽  
Hptlc Method

A stability indicating HPTLC method was developed and validated for fixed dose combination of cefpodoxime proxetil and ofloxacin. TLC plates precoated with silica gel 60F254 were used as stationary phase and n propanol: ammonia (7:3 v/v) was used as mobile phase. Densitometric scanning was carried out at 290nm. Specificity of the method was established by peak purity studies. Method was validated as per ICH guidelines Q2 (R1) for accuracy, precision, linearity, sensitivity and robustness. Both the drugs were subjected to hydrolytic (acidic and basic), oxidative, thermal and photolytic stress as per ICH guidelines Q1A (R2) and Q2B. Forced degradation studies were performed by using design of experiments approach, the most widely used mathematical model. Such experimental design approach can replace conventional trial and error experimentation to achieve optimum degradation.

Efficacy and safety of aclidinium/formoterol fixed-dose combination in patients with COPD, stratified by ICS use

Pneumologie ◽  
2016 ◽  
Vol 70 (S 01) ◽  
Author(s):  
ED Bateman ◽  
K Chapman ◽  
S Rennard ◽  
L Rekeda ◽  
M Moya ◽  
...  
Keyword(s):  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Efficacy And Safety ◽  
Dose Combination
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