Kinetic Model for Solid-State Degradation of Gabapentin

For the very first time, a detailed kinetic study for the preparation of silver nanoparticles (silver NPs) by neuroleptic agent gabapentin (GBP) in the absence of a stabilizer has been reported in this investigation. This paper is devoted to the preparation of silver nanoparticles by a chemical reduction method in which gabapentin acts as both a reductant and a stabilizer, and AgNO3 is used as a source of Ag+ ions and NaOH for maintaining the alkaline medium. A UV–visible spectrophotometer is used to monitor the progress of the reaction kinetics in an aqueous medium by changing the concentration of different variables such as AgNO3, NaOH, and gabapentin at 40 °C. It is found that the reaction rate follows a pseudo-first-order reaction. The thermodynamic activation parameters were also studied at five different temperatures (303, 308, 313, 318, and 323 K) and used in the support of the proposed mechanistic scheme for the formation of silver nanoparticles. The prepared silver nanoparticles were characterized using different techniques: UV–visible spectrophotometry, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy, and powder X-ray diffraction. The average particle size was observed in the range of 5–45 nm.

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“…It is soluble in acidic and alkaline media. At physiological pH, it was found that GBP acts as both a reducing and a stabilizing agent. ,,− …”

Section: Introductionmentioning

confidence: 99%

Detailed Kinetic and Mechanistic Study for the Preparation of Silver Nanoparticles by a Chemical Reduction Method in the Presence of a Neuroleptic Agent (Gabapentin) at an Alkaline pH and its Characterization

et al. 2022

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“…Gabapentin (GP) is usually used for epilepsy, symptoms of peripheral neuropathic pain, postherpetic neuralgia, diabetic peripheral neuropathy, acute alcohol withdrawal syndrome, and multiple sclerosis treatment [1][2][3]. Through intramolecular cyclization in solution, GP can form impurity A (ImpA)-2-azaspiro [4,5] decan-3-one, which is a European and American pharmacopoeias classification [4]. ImpA formation from crystalline GP rate depends on its polymorphic modification, temperature, moisture, shredding rate, and presence of some excipients [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

“…Through intramolecular cyclization in solution, GP can form impurity A (ImpA)-2-azaspiro [4,5] decan-3-one, which is a European and American pharmacopoeias classification [4]. ImpA formation from crystalline GP rate depends on its polymorphic modification, temperature, moisture, shredding rate, and presence of some excipients [5][6][7]. Temperature and pH of medium can influence the GP cyclization.…”

Section: Introductionmentioning

confidence: 99%

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Development and Validation of 2-Azaspiro [4,5] Decan-3-One (Impurity A) in Gabapentin Determination Method Using qNMR Spectroscopy

2021

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The authors developed a 1H qNMR test procedure for identification and quantification of impurity A present in gabapentin active pharmaceutical ingredient (API) and gabapentin products. The validation studies helped to determine the limit of quantitation and assess linearity, accuracy, repeatability, intermediate precision, specificity, and robustness of the procedure. Spike-and-recovery assays were used to calculate standard deviations, coefficients of variation, confidence intervals, bias, Fisher’s F test, and Student’s t-test for assay results. The obtained statistical values satisfy the acceptance criteria for the validation parameters. The authors compared the results of impurity A quantification in gabapentin APIs and capsules by using the 1H qNMR and HPLC test methods.

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“…Multiple potential micro-environmental and manufacturing related effects need to be integrated into rate laws to effectively describe observed behaviors. Published studies that also take into account formulation composition variables are; therefore, limited [1,2,3,4]. Polyethylene glycols (PEGs), as one of the most commonly used excipients in pharmaceutical formulations, particularly as film-coat plasticizers, have been largely investigated over recent decades in relation to their susceptibility to degradation [5,6,7,8].…”

Section: Introductionmentioning

confidence: 99%

Understanding and Kinetic Modeling of Complex Degradation Pathways in the Solid Dosage Form: The Case of Saxagliptin

et al. 2019

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Drug substance degradation kinetics in solid dosage forms is rarely mechanistically modeled due to several potential micro-environmental and manufacturing related effects that need to be integrated into rate laws. The aim of our work was to construct a model capable of predicting individual degradation product concentrations, taking into account also formulation composition parameters. A comprehensive study was done on active film-coated tablets, manufactured by layering of the drug substance, a primary amine compound saxagliptin, onto inert tablet cores. Formulation variables like polyethylene glycol (PEG) 6000 amount and film-coat polymer composition are incorporated into the model, and are connected to saxagliptin degradation, via formation of reactive impurities. Derived reaction equations are based on mechanisms supported by ab initio calculations of individual reaction activation energies. Alongside temperature, relative humidity, and reactant concentration, the drug substance impurity profile is dependent on micro-environmental pH, altered by formation of acidic PEG degradation products. A consequence of pH lowering, due to formation of formic acid, is lower formation of main saxagliptin degradation product epi-cyclic amidine, a better resistance of formulation to high relative humidity conditions, and satisfactory tablet appearance. Discovered insights enhance the understanding of degradational behavior of similarly composed solid dosage forms on overall drug product quality and may be adopted by pharmaceutical scientists for the design of a stable formulation.

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Kinetic Model for Solid-State Degradation of Gabapentin

Cited by 23 publications

References 22 publications

Detailed Kinetic and Mechanistic Study for the Preparation of Silver Nanoparticles by a Chemical Reduction Method in the Presence of a Neuroleptic Agent (Gabapentin) at an Alkaline pH and its Characterization

Detailed Kinetic and Mechanistic Study for the Preparation of Silver Nanoparticles by a Chemical Reduction Method in the Presence of a Neuroleptic Agent (Gabapentin) at an Alkaline pH and its Characterization

Development and Validation of 2-Azaspiro [4,5] Decan-3-One (Impurity A) in Gabapentin Determination Method Using qNMR Spectroscopy

Understanding and Kinetic Modeling of Complex Degradation Pathways in the Solid Dosage Form: The Case of Saxagliptin

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