Enabling thermal processing of ritonavir–polyvinyl alcohol amorphous solid dispersions by KinetiSol® Dispersing

LaFountaine, Justin S.; Jermain, Scott V.; Prasad, Leena Kumari; Brough, Chris; Miller, Dave A.; Lubda, Dieter; McGinity, James W.; Williams, Robert O.

doi:10.1016/j.ejpb.2016.01.018

Cited by 44 publications

(39 citation statements)

References 29 publications

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“…Recently, reports on a novel processing technology based on temperature and high shear force mixing have shown potential in overcoming the limitations associated with conventional hot-melt extrusion and spray-drying techniques (143,147,151). More uncommon preparation methods which are not widely used and established industrially for the preparation of amorphous formulations such as supercritical fluid impregnation /solvent-antisolvent (84,92,102,149), electrospinning /electrospraying (72,91,141,153,174), confined impinging jet (107) and pressurized gyration (161) have also been explored even though the applicability in large scale is still a question.…”

Section: Current Status Of Research On Amorphous Formulationsmentioning

confidence: 99%

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

2017

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The alarming numbers of poorly soluble discovery compounds have centered the efforts towards finding strategies to improve the solubility. One of the attractive approaches to enhance solubility is via amorphization despite the stability issue associated with it. Although the number of amorphous-based research reports has increased tremendously after year 2000, little is known on the current research practice in designing amorphous formulation and how it has changed after the concept of solid dispersion was first introduced decades ago. In this review we try to answer the following questions: What model compounds and excipients have been used in amorphous-based research? How were these two components selected and prepared? What methods have been used to assess the performance of amorphous formulation? What methodology have evolved and/or been standardized since amorphous-based formulation was first introduced and to what extent have we embraced on new methods? Is the extent of research mirrored in the number of marketed amorphous drug products? We have summarized the history and evolution of amorphous formulation and discuss the current status of amorphous formulation-related research practice. We also explore the potential uses of old experimental methods and how they can be used in tandem with computational tools in designing amorphous formulation more efficiently than the traditional trial-and-error approach.

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Section: Current Status Of Research On Amorphous Formulationsmentioning

confidence: 99%

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

2017

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“…On the other hand, most polymeric carriers have lower melting points and glass transition temperatures. Therefore, high-temperature processing can cause thermal degradation and has ultimately limited the choices of APIs and polymeric excipients suitable for HME (150). Although the introduction of plasticizers into the composition can lower the processing temperature of high melting point APIs during the preparation of ASDs via HME, the stability of ASDs can be compromised.…”

Section: Kinetisol® Dispersingmentioning

confidence: 99%

“…The study showed that KSD could effectively produce ASDs, and the optimal concentration of hydrolyzed grade PVA was 88%. Another study by LaFountaine et al also demonstrated the feasibility of processing PVA as a polymer matrix to produce ASDs with ritonavir as the active ingredient using the KSD technology, even though ritonavir is shear sensitive and can be challenging to be processed (150). The study investigated the effect of KSD rotating speed and the ejection temperature on the physicochemical properties of the products to determine the optimal range of processing parameters for complete amorphous conversion with minimal to no API and polymer degradation.…”

Section: Recent Innovations In Kinetisol® Dispersing Processing High mentioning

confidence: 99%

Innovations in Thermal Processing: Hot-Melt Extrusion and KinetiSol® Dispersing

Tan

Davis

Miller³

et al. 2020

AAPS PharmSciTech

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Thermal processing has gained much interest in the pharmaceutical industry, particularly for the enhancement of solubility, bioavailability, and dissolution of active pharmaceutical ingredients (APIs) with poor aqueous solubility. Formulation scientists have developed various techniques which may include physical and chemical modifications to achieve solubility enhancement. One of the most commonly used methods for solubility enhancement is through the use of amorphous solid dispersions (ASDs). Examples of commercialized ASDs include Kaletra®, Kalydeco®, and Onmel®. Various technologies produce ASDs; some of the approaches, such as spray-drying, solvent evaporation, and lyophilization, involve the use of solvents, whereas thermal approaches often do not require solvents. Processes that do not require solvents are usually preferred, as some solvents may induce toxicity due to residual solvents and are often considered to be damaging to the environment. The purpose of this review is to provide an update on recent innovations reported for using hot-melt extrusion and KinetiSol® Dispersing technologies to formulate poorly water-soluble APIs in amorphous solid dispersions. We will address development challenges for poorly water-soluble APIs and how these two processes meet these challenges.

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“…KinetiSol ® provides technical supplement to the hot-melt extrusion and spray-drying processes when the API is thermally labile or unstable in organic solution. For example, LaFountaine et al utilized this technique to formulate ritonavir, a drug with thermal, rheological and soluble limitations, into amorphous SDs using polyvinyl alcohol as carrier and confirmed the feasibility of this processing for production of SDs [ 79 ]. KinetiSol ® dispersing can be operated semi-continuously in a custom built device with the product throughput up to 1000 kg/h.…”

Section: Solid Dispersion Techniquementioning

confidence: 99%

Pharmaceutical Dispersion Techniques for Dissolution and Bioavailability Enhancement of Poorly Water-Soluble Drugs

et al. 2018

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Over the past decades, a large number of drugs as well as drug candidates with poor dissolution characteristics have been witnessed, which invokes great interest in enabling formulation of these active ingredients. Poorly water-soluble drugs, especially biopharmaceutical classification system (BCS) II ones, are preferably designed as oral dosage forms if the dissolution limit can be broken through. Minimizing a drug’s size is an effective means to increase its dissolution and hence the bioavailability, which can be achieved by specialized dispersion techniques. This article reviews the most commonly used dispersion techniques for pharmaceutical processing that can practically enhance the dissolution and bioavailability of poorly water-soluble drugs. Major interests focus on solid dispersion, lipid-based dispersion (nanoencapsulation), and liquisolid dispersion (drug solubilized in a non-volatile solvent and dispersed in suitable solid excipients for tableting or capsulizing), covering the formulation development, preparative technique and potential applications for oral drug delivery. Otherwise, some other techniques that can increase the dispersibility of a drug such as co-precipitation, concomitant crystallization and inclusion complexation are also discussed. Various dispersion techniques provide a productive platform for addressing the formulation challenge of poorly water-soluble drugs. Solid dispersion and liquisolid dispersion are most likely to be successful in developing oral dosage forms. Lipid-based dispersion represents a promising approach to surmounting the bioavailability of low-permeable drugs, though the technique needs to traverse the obstacle from liquid to solid transformation. Novel dispersion techniques are highly encouraged to develop for formulation of poorly water-soluble drugs.

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Enabling thermal processing of ritonavir–polyvinyl alcohol amorphous solid dispersions by KinetiSol® Dispersing

Cited by 44 publications

References 29 publications

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

Innovations in Thermal Processing: Hot-Melt Extrusion and KinetiSol® Dispersing

Pharmaceutical Dispersion Techniques for Dissolution and Bioavailability Enhancement of Poorly Water-Soluble Drugs

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