Hydrolysis in Pharmaceutical Formulations

Waterman, Kenneth C.; Adami, Roger C.; Alsante, Karen M.; Antipas, Amy S.; Arenson, Dan; Carrier, Rebecca L.; Hong, Jinyang; Landis, Margaret S.; Lombardo, Franco; Shah, Jaymin; Shalaev, Evgenyi; Smith, Scott W.; Wang, Hai

doi:10.1081/pdt-120003494

Cited by 124 publications

(45 citation statements)

References 117 publications

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“…The type and quantity of the excipients used in drug formulations can have a significant effect on final product stability (Cunningham et al 2001;Moribe et al 2007;Flemming and Picker-Freyer 2008;Islam et al 2008;Konno and Taylor 2008;Luthra et al 2012). Materials that are included in solid dosage forms contain inherent moisture, which may act both as a reagent and/or reaction medium (Waterman et al 2002). It is well established that water associated with excipients such as fillers, binders and disintegrants can cause major changes in chemical stability of admixed drugs (Monkhouse and Van Campen 1984).…”

Section: Use Of Excipients To Improve Stabilitymentioning

confidence: 98%

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Excipient Selection in Oral Solid Dosage Formulations Containing Moisture Sensitive Drugs

Rajabi‐Siahboomi

Levina²,

Upadhye

et al. 2015

Excipient Applications in Formulation Design and Drug Delivery

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Moisture sensitivity of active pharmaceutical ingredients (APIs) presents a formidable challenge in the formulation of oral dosage forms. The interaction of moisture with APIs is crucial to an understanding of water-based processes, e.g. manufacturing or prediction of solid dosage form stability and shelf-life. Unwarranted moisture sorption by either APIs or excipients can result in unstable oral solid formulations. The appropriate selection of excipients for the core formulation and appropriate moisture barrier film coating helps to remedy the moisture-related issues with APIs and thus can improve the storage stability of the final formulations. In this chapter, we review the nature and extent of the moisture sensitivity and possible approaches taken to overcome it. Use of excipients that bind tightly with water reduce its potential interaction with the API. In addition, application of a barrier coating to reduce rate and extent of moisture ingress into the core of the solid dosage form during the storage (in original packaging or while in-use), are some of the many simple options that have been considered and described.Keywords Calorimetry · Degradation · Differential scanning calorimetry · Dynamic vapor sorption · Equilibrium relative humidity · Excipients · Isothermal microcalorimetry · Moisture · Moisture-barrier coating · Near-infra red Spectroscopy · Opadry · Optical waveguide spectroscopy · Packaging · Stability · Water · Water vapor transmission rate Abbreviations AluAluminum API Active pharmaceutical ingredient

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Section: Use Of Excipients To Improve Stabilitymentioning

confidence: 98%

“…Hydrolytic reactions are amongst the most common processes for drug degradation (Waterman et al 2002;Airaksinen et al 2003Airaksinen et al , 2005aJørgensen et al 2004;Waterman and Adami 2005;Heidarian et al 2006;Luthra et al 2012).…”

Section: Effects Of Moisture In Solid Oral Dosage Formsmentioning

confidence: 99%

Excipient Selection in Oral Solid Dosage Formulations Containing Moisture Sensitive Drugs

Rajabi‐Siahboomi

Levina²,

Upadhye

et al. 2015

Excipient Applications in Formulation Design and Drug Delivery

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“…The hydrolysis of some drugs due to moisture is well documented in literature. 110,111 It can affect adversely on drug release from formulation, shelf life, handling and transportation of formulations. 26,112 Cocrystals embodiments of tramadol and paracetamol possess the ability to reduce hygroscopicity of each other.…”

Section: Impact On Physical Stabilitymentioning

confidence: 99%

Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development

Gadade¹,

Pekamwar²

2016

Adv Pharm Bull

112

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“…The most common degradation pathways involve: hydrolysis [8], hydration, oxidation [9], intramolecular cyclization, photolysis, and racemization. Many electrophilic carbonyl compounds are susceptible to hydrolysis, such as esters, lactones, amides, and lactams.…”

mentioning

confidence: 99%

Stability Challenges in Drug Discovery

Kerns

2009

Chemistry & Biodiversity

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Stability is one of the most important properties of drug candidates. Instable compounds can lead to false positive high-throughput screening (HTS) hits, incorrect bioassay results, erroneous structure-activity relationships (SAR), low oral bioavailability, drug withdrawal, toxic reactions from degradation products, and difficult formulation development. Screening of stability has been implemented early in drug discovery to identify labile chemotypes and guide structural modification. The most commonly applied stability studies in drug discovery are stability-pH profile, stability in gastrointestinal fluids, stability in bioassay media, excipient compatibility, and prodrug screening. The strategy enhances the quality of drug development candidates and reduces the risks.

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Hydrolysis in Pharmaceutical Formulations

Abstract: This literature review presents hydrolysis of active pharmaceutical ingredients as well as the effects on dosage form stability due to hydrolysis of excipients. Mechanisms and measurement methods are discussed and recommendations for formulation stabilization are listed.

Cited by 124 publications

References 117 publications

Excipient Selection in Oral Solid Dosage Formulations Containing Moisture Sensitive Drugs

Excipient Selection in Oral Solid Dosage Formulations Containing Moisture Sensitive Drugs

Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development

Stability Challenges in Drug Discovery

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