Hydroxypropyl Methylcellulose Acetate Succinate-Based Spray-Dried Dispersions: An Overview

Friesen, Dwayne T.; Shanker, Ravi; Crew, Marshall; Smithey, D. T.; Curatolo, William; Nightingale, James

doi:10.1021/mp8000793

Cited by 545 publications

(544 citation statements)

References 49 publications

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“…As a mechanistic rule, the molecular level mixing requires a step of balancing and/or breaking the crystalline lattice of drug molecules (with high activation energy) in the first instance. Subsequently, the polymer swelling (a process of polymer chain segment absorbing drug molecule) and rebuilding of the possible interactions inside the mixture occur 4 . The drug molecule (either crystalline or amorphous) may have significantly different physical properties within the polymer matrices after processing due to the different energy input and possible inter-molecular interactions that are required to form a solid dispersion.…”

Section: Introductionmentioning

confidence: 99%

“…However, the theory assumes random distribution of the segments, which may not be suitable in cases where there are strong polar forces or specific interactions, such as hydrogen 4 bonding, between the components of the blends 8 . A deeper understanding of the relatively stronger interactions between the drug and the polymer has to be built on insights of the atomic level interactions.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Modeling as a Predictive Tool for the Development of Solid Dispersions

et al. 2015

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In this study molecular modelling is introduced as a novel approach for the development of pharmaceutical solid dispersions. A computational model based on quantum mechanical (QM) calculations was used to predict the miscibility of various drugs in various polymers by predicting the binding strength between the drug and dimeric form of the polymer. The drug/polymer miscibility was also estimated by using traditional approaches such as Van Krevelen/Hoftyzer and Bagley solubility parameters or Flory Huggins interaction parameter in comparison to the molecular modelling approach.The molecular modelling studies predicted successfully the drug-polymer binding energies and the preferable site of interaction between the functional groups. The drug-polymer miscibility and the physical state of bulk materials, physical mixtures and solid dispersions were determined by thermal analysis (DSC/MTDSC) and X-ray diffraction. The produced solid dispersions were analysed by X-ray photoelectron spectroscopy (XPS), which confirmed not only the exact type of the intermolecular interactions between the drugpolymer functional groups but also the binding strength by estimating the N-coefficientvalues. The findings demonstrate that QM-based molecular modelling is a powerful tool to predict the strength and type of intermolecular interactions in a range of drug/polymeric systems for the development of solid dispersions.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular Modeling as a Predictive Tool for the Development of Solid Dispersions

et al. 2015

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“…hydroxypropylmethylcellulose or hypromellose (HPMC) (17,18). hypromellose acetate succinate (HPMCAS) (19,20). hypromellose phthalate (HPMCP) (21).…”

Section: Introductionmentioning

confidence: 99%

Use of Polyvinyl Alcohol as a Solubility-Enhancing Polymer for Poorly Water Soluble Drug Delivery (Part 1)

Brough

Miller²,

Keen³

et al. 2015

AAPS PharmSciTech

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Abstract. Polyvinyl alcohol (PVAL) has not been investigated in a binary formulation as a concentrationenhancing polymer owing to its high melting point/high viscosity and poor organic solubility. Due to the unique attributes of the KinetiSol® dispersing (KSD) technology, PVAL has been enabled for this application and it is the aim of this paper to investigate various grades for improvement of the solubility and bioavailability of poorly water soluble active pharmaceutical ingredients. Solid amorphous dispersions were created with the model drug, itraconazole (ITZ), at a selected drug loading of 20%. Polymer grades were chosen with variation in molecular weight and degree of hydroxylation to determine the effects on performance. Differential scanning calorimetry, powder X-ray diffraction, polarized light microscopy, size exclusion chromatography, and dissolution testing were used to characterize the amorphous dispersions. An in vivo pharmacokinetic study in rats was also conducted to compare the selected formulation to current market formulations of ITZ. The 4-88 grade of PVAL was determined to be effective at enhancing solubility and bioavailability of itraconazole.

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“…The increased stability of the SDD system may be due to extra energy (and thus more time) needed for the drug molecules to separate from the polymer matrix. Some spray-dried dispersions can be stable for years at room temperature (17,18), although manufacturers should take care to treat such systems as amorphous by protecting them from moisture.…”

Section: Discussionmentioning

confidence: 99%

Rationale for Selection of Dissolution Media: Three Case Studies

Fotaki¹,

Brown

Kochling

et al. 2013

Dissolution Technol.

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The selection of media in dissolution method development can sometimes be an arbitrary decision. The case studies in this article give a practical rationale that should help in selecting media, especially surfactants.Three cases were studied: (1) the role of surfactants versus compound stability in the dissolution medium during dissolution method development, (2) the selection of a surfactant based on interactions between the dissolution medium and the drug substance, and (3) the selection of media based on formulation properties.In the first case study, the choice of surfactant in relation to solubility and physical stability of the drug substance is shown. The second revealed an unexpected synergy between polysorbate 20 (Tween) and acetic acid solution that caused an unusual increase in the dissolution rate compared with these media used separately. In the last case study, the medium was modified by addition of surfactant to reflect a change in the formulation.The selection of a dissolution medium should be based on drug substance and formulation characteristics as well as on interactions among components.

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Hydroxypropyl Methylcellulose Acetate Succinate-Based Spray-Dried Dispersions: An Overview

Cited by 545 publications

References 49 publications

Molecular Modeling as a Predictive Tool for the Development of Solid Dispersions

Molecular Modeling as a Predictive Tool for the Development of Solid Dispersions

Use of Polyvinyl Alcohol as a Solubility-Enhancing Polymer for Poorly Water Soluble Drug Delivery (Part 1)

Rationale for Selection of Dissolution Media: Three Case Studies

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