Abstract:The aim of this study was to investigate the effects of various parameters at each control strategy in drug product degradation on the stability of pemetrexed in injectable aqueous solution. A forced degradation study confirmed that oxidation is the main mechanism responsible for the degradation of pemetrexed in aqueous solutions. As control strategies, the antioxidant levels, drug concentration, pH of the control formulation, dissolved oxygen (DO) levels in the control process, and headspace oxygen levels in … Show more
“…These are mainly due to the oxidation of pemetrexed. One of the studies describes pale green to yellow degradation products but these studies are not transposable to ours because of difference in mobile phase [14,15] . In this study, the degradation product B at relative retention 0.57 probably cause the yellow coloration.…”
Introduction:
A new pemetrexed salt, pemetrexed diarginine (PDA), was marketed by Mylan company. The product is a ready-to-dilute 25 mg/mL solution. The manufacturer indicates a 24-hour stability after dilution in dextrose 5% (D5W).
The objectives were to study the stability of: PDA in D5W and 0.9% sodium chloride (0.9% NaCl) polyolefin bags at 3 and 12 mg/mL protected from light (PFL) between 2 to 8°C and at 25°C, and not PFL at room temperature; PDA vials at 25 mg/mL partially used perforated with a plastic spike PFL between 2 to 8°C and at 25°C and not PFL at room temperature.
Methods:
The stability study was performed by high-performance liquid chromatography coupled to a photodiode array detector. The method was validated according to International Council for Harmonisation guideline Q2(R1). Physical stability was evaluated by visual and subvisual inspection. pH values were measured.
Results:
PDA solutions PFL in D5W and in 0.9% NaCl at 3 and 12 mg/mL retained more than 95% of the initial concentration after 7 days at 25°C and after 28 days at 2 to 8°C. PDA ready-to-dilute 25 mg/mL solutions PFL retained more than 95% of the initial concentration after 28 days at 25°C and 2 to 8°C. PDA solutions in D5W and in 0.9% NaCl at 3 mg/mL and 12 mg/mL and PDA ready-to-dilute 25 mg/mL solutions not PFL retained more than 95% of the initial concentration after 7 days at room temperature. All samples had a pH in the range of 8.05 to 8.77. A light colouration, described in SPC, to an intense yellow-brown colouration, appeared depending on concentration and time. No precipitate was observed.
Conclusion:
According to the manufacturer's specifications and to the chemical stability defined as more than 95% of the initial concentration, PDA solutions in D5W and in 0.9% NaCl at 3 and 12 mg/mL and PDA ready-to-dilute 25 mg/mL solutions PFL at 25°C and not PFL at room temperature were stable for 7 days and for 28 days at 2 to 8°C. The absence of a color change as an acceptance criterion for the 25 mg/mL ready-to-dilute solution perforated with a plastic spike leads to a stability of 7 days at 2 to 8°C and 4 days at room temperature allowing the use of the vial for a preparation in advance with an optimal stability.
“…These are mainly due to the oxidation of pemetrexed. One of the studies describes pale green to yellow degradation products but these studies are not transposable to ours because of difference in mobile phase [14,15] . In this study, the degradation product B at relative retention 0.57 probably cause the yellow coloration.…”
Introduction:
A new pemetrexed salt, pemetrexed diarginine (PDA), was marketed by Mylan company. The product is a ready-to-dilute 25 mg/mL solution. The manufacturer indicates a 24-hour stability after dilution in dextrose 5% (D5W).
The objectives were to study the stability of: PDA in D5W and 0.9% sodium chloride (0.9% NaCl) polyolefin bags at 3 and 12 mg/mL protected from light (PFL) between 2 to 8°C and at 25°C, and not PFL at room temperature; PDA vials at 25 mg/mL partially used perforated with a plastic spike PFL between 2 to 8°C and at 25°C and not PFL at room temperature.
Methods:
The stability study was performed by high-performance liquid chromatography coupled to a photodiode array detector. The method was validated according to International Council for Harmonisation guideline Q2(R1). Physical stability was evaluated by visual and subvisual inspection. pH values were measured.
Results:
PDA solutions PFL in D5W and in 0.9% NaCl at 3 and 12 mg/mL retained more than 95% of the initial concentration after 7 days at 25°C and after 28 days at 2 to 8°C. PDA ready-to-dilute 25 mg/mL solutions PFL retained more than 95% of the initial concentration after 28 days at 25°C and 2 to 8°C. PDA solutions in D5W and in 0.9% NaCl at 3 mg/mL and 12 mg/mL and PDA ready-to-dilute 25 mg/mL solutions not PFL retained more than 95% of the initial concentration after 7 days at room temperature. All samples had a pH in the range of 8.05 to 8.77. A light colouration, described in SPC, to an intense yellow-brown colouration, appeared depending on concentration and time. No precipitate was observed.
Conclusion:
According to the manufacturer's specifications and to the chemical stability defined as more than 95% of the initial concentration, PDA solutions in D5W and in 0.9% NaCl at 3 and 12 mg/mL and PDA ready-to-dilute 25 mg/mL solutions PFL at 25°C and not PFL at room temperature were stable for 7 days and for 28 days at 2 to 8°C. The absence of a color change as an acceptance criterion for the 25 mg/mL ready-to-dilute solution perforated with a plastic spike leads to a stability of 7 days at 2 to 8°C and 4 days at room temperature allowing the use of the vial for a preparation in advance with an optimal stability.
“…8 . Mainly pH reduction observation was due to hydrolysis (LoR might undergo hydrolysis usually at high temperatures) or oxidation with chemical reactions and degradation of buffers in the formulations 39 . The stability study conclude that the optimized formulation should remain stable when topically applied in humans.…”
Loratadine (LoR) is a highly lipophilic and practically insoluble in water, hence having a low oral bioavailability. As it is formulated as topical gel, it competitively binds with the receptors, thus reducing the side-effects. The objective of this study was to prepare LoR loaded nanosponge (LoR-NS) in gel for topical delivery. Nine different formulations of emulsion were prepared by solvent evaporation method with polyvinyl alcohol (PVA), ethyl cellulose (EC), and dichloromethane (DCM). Based on 32 Full Factorial Design (FFD), optimization was carried out by varying the concentration of LOR:EC ratio and stirring rate. The preparations were subjected for the evaluation of particle size (PS), in vitro release, zeta potential (ZP) and entrapment efficiency (EE). The results revealed that the NS dispersion was nanosized with sustained release profiles and significant PS. The optimised formulation was formulated and incorporated into carbopol 934P hydrogel. The formulation was then examined to surface morphological characterizations using scanning electron microscopy (SEM) which depicted spherical NS. Stability studies, undertaken for 2 months at 40 ± 2 °C/75 ± 5% RH, concluded to the stability of the formulation. The formulation did not cause skin irritation. Therefore, the prepared NS hydrogel proved to be a promising applicant for LoR as a novel drug delivery system (NDDS) for safe, sustained and controlled topical application.
“…These results indicate that protection of protein formulations from photodegradation can be achieved by minimization of the oxygen content headspace of the primary container or the use of inert gas instead of air ( Qi et al, 2009 ). Thus, reducing the oxygen content in the headspace and using an impermeable oxygen packaging material may lead to a less pronounced photooxidation for light sensitive proteins ( Gupta et al, 2021 ; Masato et al, 2015 ; Won et al, 2020 ; Härdter et al, 2021 ; Landi and Held, 1986 ). Fig.…”
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