ChemInform Abstract: Drug Solubility: Importance and Enhancement Techniques

Savjani, Ketan; Anuradha, G; Savjani, Jignasa

doi:10.1002/chin.201326246

Cited by 4 publications

(4 citation statements)

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“…26,27 Polymorphism is estimated to occur in up to 80% of molecules that display pharmaceutical applications, 27,28 affecting properties of the solid state (stability, solubility, dissolution rate, and bioavailability), and therefore, the quality and efficacy of the final drug product. 24,26,27,[29][30][31][32] The unsubstantiated notion that undesired polymorphic phase transformations might occur during HME limits the application of this technique to produce crystalline solid dispersions for a narrow set of APIs that are both thermally stable and monomorphic (∼20%). 27,28 However, taking into consideration other industrial processes, this sentiment might be founded on insufficient knowledge of the thermodynamic and kinetic boundaries, in other words, the design space of a particular HME process.…”

Section: Introductionmentioning

confidence: 99%

Revealing Polymorphic Phase Transformations in Polymer-Based Hot Melt Extrusion Processes

Espinell

López-Mejías

Stelzer

2018

Crystal Growth & Design

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The inadvertent occurrence of polymorphic phase transformations in active pharmaceutical ingredients (APIs) during hot melt extrusion (HME) processes has been claimed to limit the application of this technique. Hence, the control of polymorphism would need to be addressed if there is any prospect of HME to be successfully implemented as an alternative solid dosage formulation strategy in integrated, continuous end-to-end pharmaceutical manufacturing settings. This work demonstrates that flufenamic acid (FFA), one of the most polymorphic APIs known, thus far, can be processed using temperature-simulated HME with polyethylene glycol (PEG) as polymeric carrier. At temperatures above the transition point of FFA forms III and I (42 °C), the induction time of the polymorphic phase transformation is longer than the average reported residence time in conventional HME processes (5 min). Moreover, it was demonstrated that thorough understanding of the thermodynamic and kinetic design space for the PEG-FFA system leads to polymorphic control in the produced crystalline solid dispersions. Ultimately, this investigation helps to gain fundamental understanding of the processing needs of crystalline solid dispersions, which will lead to the broader application of HME as a continuous manufacturing strategy for drug products containing APIs prone to polymorphism, representing about 80% of all APIs.

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Section: Introductionmentioning

confidence: 99%

Revealing Polymorphic Phase Transformations in Polymer-Based Hot Melt Extrusion Processes

Espinell

López-Mejías

Stelzer

2018

Crystal Growth & Design

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“…Hence many of these promising active compounds are not considered in clinical-stage development [6]. Solubility of the drug is one of the major parameter to achieve the desired drug concentration in systemic circulation to produce therapeutic activity when administered [9]. The drug dissolution and gastro-intestinal permeability are the fundamental properties controlling the rate and extent of drug absorption [8].…”

Section: Introductionmentioning

confidence: 99%

“…The conventional techniques are salt forms, solid dispersions [16], use of co-solvents [12], hydrotropy, micronization, change in dielectric constant of solvent, amorphous forms [7], chemical modification of drug, use of surfactants, inclusion complex [3], alteration of pH of solvent, use of hydrates or solvates [6], use of soluble prodrugs [8], application of ultrasonic waves [9], functional polymer technology, controlled precipitation technology [12], evaporative precipitation in aqueous solution [18], use of precipitation inhibitors, solvent deposition [4], precipitation [2], selective adsorption on insoluble carriers [9]. However, conventional approaches have many limitations like for example salt formation [12] of drugs is commonly used but always unattainable.…”

Section: Introductionmentioning

confidence: 99%

Snedds as Lipid-Based Nanocarrier Systems: Concepts and Formulation Insights

GOTTEMUKKULA

Sampathi

2022

Int J App Pharm

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Approximately 40 % of newly discovered chemical entities have low solubility and possess low bioavailability after oral administration. Lipid-based drug delivery systems (LBDDS) have recently become very popular because of their remarkable ability to deliver drugs with poor absorption using lipids as carriers. Self-emulsifying drug delivery (SEDDS) systems are one type of LBDDS employed for the incorporation of hydrophobic drugs. SEDDS are classified into self-micro emulsifying drug delivery systems (SMEDDS) and self-nano emulsifying drug delivery systems (SNEDDS) based on the droplet size of the dispersed phase. The present review focus on the mechanism of drug absorption from lipid-based nanocarriers systems, in vitro assessment of self-emulsification, insights of SNEDDS, factors affecting the formulation of SNEDDS, and its applications.

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“…Compared to Sor, Sor-Tos has a higher solubility, a higher bioavailability, and a lower side effect [ 7 , 8 ], but its aqueous solubility is still low, leading to its slight absorption in the gastrointestinal tract [ 9 , 10 ]. Therefore, the dissolution rate plays a vital role in increasing the bioavailability of Sor-Tos, especially when a slight increase in the dissolution rate can produce a significant improvement in bioavailability [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of Crystal Habit on the Dissolution Rate and In Vivo Pharmacokinetics of Sorafenib Tosylate

Phan

Shen

et al. 2021

Molecules

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The dissolution rate is the rate-limiting step for Biopharmaceutics Classification System (BCS) class II drugs to enhance their in vivo pharmacokinetic behaviors. There are some factors affecting the dissolution rate, such as polymorphism, particle size, and crystal habit. In this study, to improve the dissolution rate and enhance the in vivo pharmacokinetics of sorafenib tosylate (Sor-Tos), a BCS class II drug, two crystal habits of Sor-Tos were prepared. A plate-shaped crystal habit (ST-A) and a needle-shaped crystal habit (ST-B) were harvested by recrystallization from acetone (ACN) and n-butanol (BuOH), respectively. The surface chemistry of the two crystal habits was determined by powder X-ray diffraction (PXRD) data, molecular modeling, and face indexation analysis, and confirmed by X-ray photoelectron spectroscopy (XPS) data. The results showed that ST-B had a larger hydrophilic surface than ST-A, and subsequently a higher dissolution rate and a substantial enhancement of the in vivo pharmacokinetic performance of ST-B.

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ChemInform Abstract: Drug Solubility: Importance and Enhancement Techniques

Abstract: Review: 71 refs.

Cited by 4 publications

References 0 publications

Revealing Polymorphic Phase Transformations in Polymer-Based Hot Melt Extrusion Processes

Revealing Polymorphic Phase Transformations in Polymer-Based Hot Melt Extrusion Processes

Snedds as Lipid-Based Nanocarrier Systems: Concepts and Formulation Insights

Impact of Crystal Habit on the Dissolution Rate and In Vivo Pharmacokinetics of Sorafenib Tosylate

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