Optimizing the Formulation of Poorly Water-Soluble Drugs

O’Donnell, K. P.; Williams, Robert O.

doi:10.1007/978-1-4614-1144-4_2

Cited by 8 publications

(6 citation statements)

References 128 publications

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“…For example, hot-melt extrusion (HME) is a viable technology that employs thermal processing of polymers and crystalline drugs. Numerous reviews of this subject have been published elsewhere. − Compared to HME, spray drying can be advantageous if the API or excipient degrades at high processing temperatures or if the API is prohibitively expensive during preclinical development. Williams et al have chronicled the rise of solubility and dissolution enhancement techniques for poorly water-soluble drugs, which includes an account comparing how pharmaceutical products have adapted solid-dispersion technology as well as other solubility-enhancing techniques over time .…”

Section: Introductionmentioning

confidence: 99%

Advances in Polymer Design for Enhancing Oral Drug Solubility and Delivery

et al. 2018

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Synthetic polymers have enabled amorphous solid dispersions (ASDs) to emerge as an oral delivery strategy for overcoming poor drug solubility in aqueous environments. Modern ASD products noninvasively treat a range of chronic diseases (for example, hepatitis C, cystic fibrosis, and HIV). In such formulations, polymeric carriers generate and maintain drug supersaturation upon dissolution, increasing the apparent drug solubility to enhance gastrointestinal barrier absorption and oral bioavailability. In this Review, we outline several approaches in designing polymeric excipients to drive interactions with active pharmaceutical ingredients (APIs) in spray-dried ASDs, highlighting polymer-drug formulation guidelines from industrial and academic perspectives. Special attention is given to new commercial and specialized polymer design strategies that can solubilize highly hydrophobic APIs and suppress the propensity for rapid drug recrystallization. These molecularly customized excipients and hierarchical excipient assemblies are promising toward informing early-stage drug-discovery development and reformulating existing API candidates into potentially lifesaving oral medicines for our growing global population.

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Section: Introductionmentioning

confidence: 99%

Advances in Polymer Design for Enhancing Oral Drug Solubility and Delivery

et al. 2018

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“…Around 60% of drugs that are screened during industrial research are poorly water-soluble. 1 Therefore, the enhancement of poorly soluble drugs is becoming increasingly important in industry and research.…”

Section: ■ Introductionmentioning

confidence: 99%

Continuous Cocrystallization for Dissolution Rate Optimization of a Poorly Water-Soluble Drug

Moradiya

Islam

Woollam

et al. 2013

Crystal Growth & Design

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A continuous manufacturing process, hot melt extrusion (HME), was employed for the development of high quality carbamazepine−saccharin (CBZ−SCH) cocrystals. The produced cocrystals were compared with a prototype prepared by a solvent method. It was found that processing parameters such as temperature, screw speed, and screw configuration were the critical processing parameters. In-line near-infrared analysis demonstrated that cocrystallization takes place gradually during the process along the extruder's mixing zones. Further characterization of the extruded cocrystals proved that the manufactured highly crystalline cocrystals were similar to the prototype but had improved CBZ dissolution rates. Continuous manufacturing of cocrystals of water-insoluble drugs is a novel and robust approach.

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“…There is currently very strong demand for new drug delivery systems (DDSs) suitable for the chosen administration route and able to deliver APIs to particular sites, to limit adverse reactions and side effects, and to improve patient comfort (1). Microencapsulation is a technological strategy that seems to perform well, particularly not only for APIs with a short half-life that are rapidly hydrolysed or broken down by enzymes in vivo but also for APIs with low solubility or poor permeation characteristics (3,4).…”

Section: Introductionmentioning

confidence: 99%

Spray-Dried Succinylated Soy Protein Microparticles for Oral Ibuprofen Delivery

et al. 2019

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The potential value of succinylated soy protein (SPS) as a wall material for the encapsulation of ibuprofen (IBU), a model hydrophobic drug, by spray-drying was investigated. A succinylation rate of 93% was obtained for soy protein isolate, with a molar ratio of 1/1.5 (NH 2 /succinic anhydride). The solubility profile at 37°C showed that this chemical modification decreased the solubility of the protein below its isoelectric point, whereas solubility increased in alkaline conditions. Various SPS/IBU ratios (90/10, 80/20, and 60/40) were studied and compared with the same ratio of soy protein isolate (SPI/IBU). High encapsulation efficiency was achieved (91-95%). Microparticles were spherical and between 4 and 8 μm in diameter. The spray-drying of protein/IBU solutions appeared to be beneficial, as it resulted in an amorphous solid dispersion of IBU within the microparticles, coupled with an increase in the thermal stability of IBU. In vitro release was evaluated in acidic (pH 1.2 in the presence of pepsin) and neutral (pH 6.8) conditions similar to those in the gastrointestinal (GI) tract. IBU was released significantly more slowly at pH 1.2, for both proteins. However, this slowing was particularly marked for SPS, for which rapid (within 2 h) and complete release was observed at pH 6.8. These results validate the hypothesis that SPS is suitable for use as a coating material for hydrophobic active pharmaceutical ingredients (APIs) due to its pH sensitivity, which should delay IBU release in the gastrointestinal tract.

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Optimizing the Formulation of Poorly Water-Soluble Drugs

Cited by 8 publications

References 128 publications

Advances in Polymer Design for Enhancing Oral Drug Solubility and Delivery

Advances in Polymer Design for Enhancing Oral Drug Solubility and Delivery

Continuous Cocrystallization for Dissolution Rate Optimization of a Poorly Water-Soluble Drug

Spray-Dried Succinylated Soy Protein Microparticles for Oral Ibuprofen Delivery

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