Characterization of Physico-Mechanical Properties of Indomethacin and Polymers to Assess their Suitability for Hot-Melt Extrusion Processs as a Means to Manufacture Solid Dispersion/Solution**Mailing address of the place where the work was carried out, Hoffmann-La Roche, Inc., 340 Kingsland Street, Nutley, NJ, 07110.

Chokshi, Rina; Sandhu, Harpreet; Iyer, Raman; Shah, Navnit; Malick, A. Waseem; Zia, Hossein

doi:10.1002/jps.20385

Cited by 179 publications

(106 citation statements)

References 12 publications

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“…The T g is more than 10°C higher (roughly 20%) than KSD compositions with 4-38 and 4-75 grades as well as the pure 4-88 polymer and is close to the T g of pure amorphous itraconazole. The anti-plasticizing effect of amorphous ITZ on the 4-88 grade indicates strong positive drug-polymer interactions (16). The increased T g relative to the other PVAL grades seems to also support the previously discussed hypothesis regarding an optimal ratio of PVAC to PVAL at which hydrogen bonding or hydrophilic/ hydrophobic locations are maximized.…”

Section: Solid-state Analysissupporting

confidence: 80%

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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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Section: Solid-state Analysissupporting

confidence: 80%

“…polyethyleneglycols (PEG) (13,14). polymethacrylates (15,16). hydroxypropylmethylcellulose or hypromellose (HPMC) (17,18).…”

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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show abstract

“…Both formulations showed significant reductions in die pressure at the lower processing temperature evaluated. APIs with miscibility in a polymer can also contribute a plasticizing effect on a formulation (48,49 in softening temperature was observed, allowing for HME processing at temperatures around 150°C. Given the plasticization effect of GRIS (T g =~89°C, Tm=~220°C; (31)), as observed by a decrease in T g in MDSC experiments, a higher drug loading could allow for further reduction in viscosity of high molecular weight polymer grades to enable extrusion processing.…”

Section: Discussionmentioning

confidence: 99%

Thermal Processing of PVP- and HPMC-Based Amorphous Solid Dispersions

et al. 2015

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Abstract. Thermal processing technologies continue to gain interest in pharmaceutical manufacturing. However, the types and grades of polymers that can be utilized in common thermal processing technologies, such as hot-melt extrusion (HME), are often limited by thermal or rheological factors. The objectives of the present study were to compare and contrast two thermal processing methods, HME and KinetiSol® Dispersing (KSD), and investigate the influence of polymer type, polymer molecular weight, and drug loading on the ability to produce amorphous solid dispersions (ASDs) containing the model compound griseofulvin (GRIS). Dispersions were analyzed by a variety of imaging, solid-state, thermal, and solution-state techniques. Dispersions were prepared by both HME and KSD using polyvinylpyrrolidone (PVP) K17 or hydroxypropyl methylcellulose (HPMC) E5. Dispersions were only prepared by KSD using higher molecular weight grades of HPMC and PVP, as these could not be extruded under the conditions selected. Powder X-ray diffraction (PXRD) analysis showed that dispersions prepared by HME were amorphous at 10% and 20% drug load; however, it showed significant crystallinity at 40% drug load. PXRD analysis of KSD samples showed all formulations and drug loads to be amorphous with the exception of trace crystallinity seen in PVP K17 and PVP K30 samples at 40% drug load. These results were further supported by other analytical techniques. KSD produced amorphous dispersions at higher drug loads than could be prepared by HME, as well as with higher molecular weight polymers that were not processable by HME, due to its higher rate of shear and torque output.

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“…It has been reported that SDs were prepared with a water-soluble Kollidon system by different methods. [11][12][13] It also have been reported that SDs of nilvadipine were prepared using crospovidone and methylcellulose as dispersion carriers, and SDs of indomethacin were prepared with crospovidone as a carrier by a hot-melt extrusion processs. 14,15) Ibuprofen (IBU) is one of the safest and most potent nonsteroidal anti-inflammatory drugs, being widely used in the market for 30 years.…”

mentioning

confidence: 99%

Preparation and Evaluation of Ibuprofen Solid Dispersion Systems with Kollidon Particles Using a Pulse Combustion Dryer System

Sunada

2007

CHEMICAL & PHARMACEUTICAL BULLETIN

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Cited by 179 publications

References 12 publications

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

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

Thermal Processing of PVP- and HPMC-Based Amorphous Solid Dispersions

Preparation and Evaluation of Ibuprofen Solid Dispersion Systems with Kollidon Particles Using a Pulse Combustion Dryer System

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