Gabapentin–saccharin co-crystals with enhanced physicochemical properties and<i>in vivo</i>absorption formulated as oro-dispersible tablets

Soliman, Iman; Kandil, Soha M; Abdou, Ebtsam M

doi:10.1080/10837450.2019.1687521

Cited by 21 publications

(9 citation statements)

References 35 publications

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“…The co-crystallization of active pharmaceutical ingredients (APIs) with coformers offers a unique way to improve key physicochemical properties without changing the chemical nature and pharmacological activity of APIs [ 1 , 2 ]. Solubility, dissolution rate, bioavailability [ 3 , 4 , 5 , 6 , 7 , 8 ], melting point [ 9 ], stability [ 10 , 11 , 12 ], tabletability [ 13 ], taste [ 6 ], and other properties can undergo change during co-crystallization. Orally disintegrating tablets consisting of gabapentin co-crystals (antiepileptic and analgesic agent) with saccharin (sweetener) have shown a number of benefits in comparison to the same formulation with a physical mixture of starting components [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Structural Characterization of Co-Crystals of Chlordiazepoxide with p-Aminobenzoic Acid and Lorazepam with Nicotinamide by DSC, X-ray Diffraction, FTIR and Raman Spectroscopy

et al. 2020

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The low water solubility of benzodiazepines seriously affects their bioavailability and, in consequence, their biological activity. Since co-crystallization has been found to be a promising way to modify undesirable properties in active pharmaceutical ingredients, the objective of this study was to prepare co-crystals of two benzodiazepines, chlordiazepoxide and lorazepam. Using different co-crystallization procedures, slurry evaporation and liquid-assisted grinding, co-crystals of chlordiazepoxide with p-aminobenzoic acid and lorazepam with nicotinamide were prepared for the first time. Confirmation that co-crystals were obtained was achieved through a comparison of the data acquired for both co-crystals using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier-transform infrared (FTIR) and Raman spectroscopy, with comparisons acquired for the physical mixtures of both benzodiazepines and coformers. The compatibility of PXRD patterns of both benzodiazepines co-crystals with those contained in the base Powder Diffraction File (PDF-4+) suggests that new crystal structures were indeed created under the co-crystallization procedure. Single-crystal X-ray diffraction revealed that a chlordiazepoxide co-crystal with p-aminobenzoic acid and a lorazepam co-crystal with nicotinamide crystallized in the monoclinic P21/n and P21/c space group, respectively, with one molecule of benzodiazepine and one of coformer in the asymmetric unit. FTIR and Raman spectroscopy corroborated that benzodiazepine and coformer are linked by a hydrogen bond without proton exchange. Furthermore, a DSC study revealed that single endothermic DSC peaks assigned to the melting of co-crystals differ slightly depending on the co-crystallization procedures and solvent used, as well as differing from those of starting components.

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Section: Introductionmentioning

confidence: 99%

Structural Characterization of Co-Crystals of Chlordiazepoxide with p-Aminobenzoic Acid and Lorazepam with Nicotinamide by DSC, X-ray Diffraction, FTIR and Raman Spectroscopy

et al. 2020

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“…Mean plasma concentration of gabapentin in rabbits when treated with gabapentin and its cocrystal and physical mixture with saccharin. Adapted with permission from ref . Copyright 2020 Taylor & Francis.…”

Section: Sustainability: Conventional and Cocrystal-based Drug Produc...mentioning

confidence: 99%

Optimizing Drug Development: Harnessing the Sustainability of Pharmaceutical Cocrystals

Aitipamula,

Bolla

2024

Mol. Pharmaceutics

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Environmental impacts of the industrial revolution necessitate adoption of sustainable practices in all areas of development. The pharmaceutical industry faces increasing pressure to minimize its ecological footprint due to its significant contribution to environmental pollution. Over the past two decades, pharmaceutical cocrystals have received immense popularity due to their ability to optimize the critical attributes of active pharmaceutical ingredients and presented an avenue to bring improved drug products to the market. This review explores the potential of pharmaceutical cocrystals as an ecofriendly alternative to traditional solid forms, offering a sustainable approach to drug development. From reducing the number of required doses to improving the stability of actives, from eliminating synthetic operations to using pharmaceutically approved chemicals, from the use of continuous and solvent-free manufacturing methods to leveraging published data on the safety and toxicology, the cocrystallization approach contributes to sustainability of drug development. The latest trends suggest a promising role of pharmaceutical cocrystals in bringing novel and improved medicines to the market, which has been further fuelled by the recent guidance from the major regulatory agencies.

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“…The crystalline material, which consists of drugs and sweetener molecules such as sucralose or saccharin, is known as the sweet cocrystal. , Through different designs, the cocrystals can exhibit very different physicochemical properties from the parent API in terms of solubility, dissolution, hygroscopicity, and taste . For example, cocrystals with saccharin as the cocrystal former can improve the wettability of raw drugs, beneficial to the disintegration of orodispersible dosage forms. , In terms of taste improvement, Soloman et al found that the orodispersible tablet of gabapentin–saccharin sweet cocrystals exhibited lower wettability, shorter disintegration time ( p < 0.05), and better taste compared with physical mixtures of gabapentin–saccharin in the same dosage as sweeteners . In recent years, sweet cocrystals have been widely applied to improve drug bioavailability, with great potential in taste masking.…”

Section: Time-intensity Taste Maskingmentioning

confidence: 99%

“…11,13 In terms of taste improvement, Soloman et al found that the orodispersible tablet of gabapentin− saccharin sweet cocrystals exhibited lower wettability, shorter disintegration time (p < 0.05), and better taste compared with physical mixtures of gabapentin−saccharin in the same dosage as sweeteners. 14 In recent years, sweet cocrystals have been widely applied to improve drug bioavailability, with great potential in taste masking. However, it is worth noting that different cocrystal formers possess various changes in drug properties so that the effect of taste masking depends on the selection of corresponding cocrystal formers for drugs.…”

Section: Shortening Disintegration Time Of Tabletsmentioning

confidence: 99%

Strategies for Taste Masking of Orodispersible Dosage Forms: Time, Concentration, and Perception

Xie

et al. 2022

Mol. Pharmaceutics

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Orodispersible dosage forms, characterized as quick dissolving and swallowing without water, have recently gained great attention from the pharmaceutical industry, as these forms can satisfy the needs of children, the elderly, and patients suffering from mental illnesses. However, poor taste by thorough exposure of the drugs’ dissolution in the oral cavity hinders the effectiveness of the orodispersible dosage forms. To bridge this gap, we put forward three taste-masking strategies with respect to the intensity of time, concentration, and perception. We further investigated the raw material processing, the composition of auxiliary material, formulation techniques, and process control in each strategy and drew conclusions about their effects on taste masking.

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Gabapentin–saccharin co-crystals with enhanced physicochemical properties andin vivoabsorption formulated as oro-dispersible tablets

Cited by 21 publications

References 35 publications

Structural Characterization of Co-Crystals of Chlordiazepoxide with p-Aminobenzoic Acid and Lorazepam with Nicotinamide by DSC, X-ray Diffraction, FTIR and Raman Spectroscopy

Structural Characterization of Co-Crystals of Chlordiazepoxide with p-Aminobenzoic Acid and Lorazepam with Nicotinamide by DSC, X-ray Diffraction, FTIR and Raman Spectroscopy

Optimizing Drug Development: Harnessing the Sustainability of Pharmaceutical Cocrystals

Strategies for Taste Masking of Orodispersible Dosage Forms: Time, Concentration, and Perception

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