Stabilization of the maleate salt of a basic drug by adjustment of microenvironmental pH in solid dosage form

Zannou, Erika A.; Ji, Qin; Joshi, Yatindra M.; Serajuddin, Abu T.M.

doi:10.1016/j.ijpharm.2007.01.005

Cited by 84 publications

(50 citation statements)

References 6 publications

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“…The physical observations were supported by PXRD spectra, which were devoid of any peaks owing to crystalline structure. The phenomenon was similar to that reported for a maleate salt of an anti-Parkinsonian drug (10).…”

Section: Solid-state Phase Transformations Among the Investigated Formssupporting

confidence: 89%

Influence of Microenvironment pH, Humidity, and Temperature on the Stability of Polymorphic and Amorphous Forms of Clopidogrel Bisulfate

2010

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Abstract. The effect of microenvironment pH, humidity, and temperature was evaluated on the stability of polymorphic and amorphous forms of clopidogrel bisulfate, when present alone or in combinations. Oxalic acid and sodium carbonate were used as solid stressors to create acidic and alkaline pH, respectively. The samples without and with stressors were subjected for 3 months to (1) 0% RH, 25% RH, 75% RH, and 85% RH at 40°C and also to (2) 60°C, 80°C, and 100°C at 0% RH. In case of solid samples without stressors, the mixture of polymorphic and amorphous forms showed more degradation than the individual forms above critical relative humidity (85% RH). Similar higher degradation was observed between 75% RH and 85% RH in case of acid-stressed samples. In alkaline microenvironment, all the samples showed identical decomposition attributed to conversion of bisulfate salt to free base. Thermal studies indicated that polymorphic forms of clopidogrel bisulfate and also its glassy amorphous form were highly resistant to temperature, whereas the rubbery state of the drug degraded significantly at temperatures of ≥80°C.

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Section: Solid-state Phase Transformations Among the Investigated Formssupporting

confidence: 89%

Influence of Microenvironment pH, Humidity, and Temperature on the Stability of Polymorphic and Amorphous Forms of Clopidogrel Bisulfate

2010

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“…pHM modifier technology, which involves adding an acidifier or alkalizer to formulations containing weakly basic or acidic drugs, respectively, was used extensively to improve the solubility, obtain pH independence, and achieve sustained drug release (98,99). Especially for weakly basic drugs, the use of acidic excipients enabled a more robust formulation less susceptible to variance in gastric pH, improved the observed variability, and achieved adequate exposure under high gastric pH conditions (100).…”

Section: Microenvironment Ph-modified Drug Delivery Systemsmentioning

confidence: 99%

Bioavailability Improvement Strategies for Poorly Water-Soluble Drugs Based on the Supersaturation Mechanism: An Update

Yang¹,

Gong²,

Wang³

et al. 2016

J Pharm Pharm Sci

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-The formulation development for poorly soluble drugs still remains a challenge. Supersaturating drug delivery systems (SDDS) or drug delivery systems based on supersaturating provide a promising way to improve the oral bioavailability of poorly water-soluble drugs. In supersaturable formulations, drug concentration exceeds the equilibrium solubility when exposed to gastrointestinal fluids, and the supersaturation state is maintained long enough to be absorbed, resulting in compromised bioavailability. In this article, the mechanism of generating and maintaining supersaturation and the evaluation methods of supersaturation assays are discussed. Recent advances in different drug delivery systems based on supersaturating are the focus and are discussed in detail.

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“…In fact, the slurry pH will be dependent on the concentration of solid in the slurry, and this could be significantly different from the actual hydrogen ion activity in the solid dosage form. However, microenvironmental pH measured using the slurry method has demonstrated some success in correlating with the stability of immediate release formulations [11,12] and identifying the level of pH-modifying agent needed to provide the required microenvironmental pH which minimises the risk of salt disproportionation [13].…”

Section: Determination Of Microenvironmental Ph Using a Ph Metermentioning

confidence: 99%

Microenvironmental pH Control and Mixed Polymer Approaches to Optimise Drug Delivery with Hydrophilic Matrix Tablets

Timmins

Pygall

2014

Hydrophilic Matrix Tablets for Oral Controlled Release

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Stabilization of the maleate salt of a basic drug by adjustment of microenvironmental pH in solid dosage form

Cited by 84 publications

References 6 publications

Influence of Microenvironment pH, Humidity, and Temperature on the Stability of Polymorphic and Amorphous Forms of Clopidogrel Bisulfate

Influence of Microenvironment pH, Humidity, and Temperature on the Stability of Polymorphic and Amorphous Forms of Clopidogrel Bisulfate

Bioavailability Improvement Strategies for Poorly Water-Soluble Drugs Based on the Supersaturation Mechanism: An Update

Microenvironmental pH Control and Mixed Polymer Approaches to Optimise Drug Delivery with Hydrophilic Matrix Tablets

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