Influence of Process and Formulation Parameters on Dissolution and Stability Characteristics of Kollidon® VA 64 Hot-Melt Extrudates

Maddineni, Sindhuri; Battu, Sunil Kumar; Morott, Joe; Majumdar, Soumyajit; Murthy, S. N. B.; Repka, Michael A.

doi:10.1208/s12249-014-0226-4

Cited by 32 publications

(13 citation statements)

References 22 publications

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“…The drawbacks associated with HME are usually related to the exposure of the product to high processing temperatures for relatively long residence times. Processing of APIs that have high melting points or are thermally labile continues to be a challenge due to energy input required during HME to produce an amorphous final product (17,18). Additionally, higher molecular weight polymers that may be effective for stabilizing the amorphous drug may be too viscous for processing via HME due to high torque loads, requiring the use of plasticizers that decrease the final product glass transition temperature (19)(20)(21)(22).…”

Section: Introductionmentioning

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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Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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“…Assay of MA in the extrudates confirmed that the extrudates were chemically stable, with no drug degradation when analyzed for the drug content after storage duration (>99%, within 1% difference) 37 . DSC analysis demonstrated that the drug remained in an amorphous form, as the corresponding endothermic peak was not present after 6 months of storage (Figure 11-a & 12-a).…”

Section: Resultsmentioning

confidence: 69%

Investigation of the combined effect of MgO and PEG on the release profile of mefenamic acid prepared via hot-melt extrusion techniques

Alshehri

Tiwari

Alsulays

et al. 2016

Pharmaceutical Development and Technology

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This study aimed to investigate the combined effect of magnesium oxide (MgO) as an alkalizer and polyethylene glycol (PEG) as a plasticizer and wetting agent in the presence of Kollidon® 12 PF and 17 PF polymer carriers on the release profile of mefenamic acid (MA), which was prepared via hot-melt extrusion (HME) technique. Various drug loads of MA and various ratios of the polymers, PEG 3350, and MgO were blended using a V-shell blender and extruded using a twin-screw extruder (16-mm Prism EuroLab, ThermoFisher Scientific) at different screw speeds and temperatures to prepare a solid dispersion system. Differential scanning calorimetry and X-ray diffraction data of the extruded material confirmed that the drug existed in the amorphous form, as evidenced by the absence of corresponding peaks. MgO and PEG altered the micro-environmental pH to be more alkaline (pH 9) and increased the hydrophilicity and dispersibility of the extrudates to enhance MA solubility and release, respectively. The in vitro release study demonstrated an immediate release for 2 h with more than 80% drug release within 45 min in matrices containing MgO and PEG in combination with PVP, when compared to the binary mixture, physical mixture, and pure drug.

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“…As expected, CE showed a low flowability (=49), proving its poor flow capacity ( Table 2 ). Meanwhile, HME extrudates showed flowability in the range of 71–88, demonstrating a remarkable improvement of this property, which enables this processed natural product to be used in direct compression of tablets or to fill capsules, without any additional processing [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

Dissolution Enhancement in Cocoa Extract, Combining Hydrophilic Polymers through Hot-Melt Extrusion

et al. 2018

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The aim of this study was to improve the physicochemical properties of cocoa extract (CE) using hot-melt extrusion (HME) for pharmaceutical proposes. A mixture design was applied using three distinct hydrophilic polymeric matrices (Soluplus, Plasdone S630, and Eudragit E). Systems obtained by HME were evaluated using morphologic, chromatographic, thermic, spectroscopic, and diffractometric assays. The flow, wettability, and dissolution rate of HME powders were also assessed. Both CE and its marker theobromine proved to be stable under heating according to thermal analysis and Arrhenius plot under isothermal conditions. Physicochemical analysis confirmed the stability of CE HME preparations and provided evidence of drug–polymer interactions. Improvements in the functional characteristics of CE were observed after the extrusion process, particularly in dissolution and flow properties. In addition, the use of a mixture design allowed the identification of synergic effects by excipient combination. The optimized combination of polymers obtained considering four different aspects showed that a mixture of the Soluplus, Plasdone S630, and Eudragit E in equal proportions produced the best results (flowability index 88%; contact angle 47°; dispersibility 7.5%; and dissolution efficiency 87%), therefore making the pharmaceutical use of CE more feasible.

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Influence of Process and Formulation Parameters on Dissolution and Stability Characteristics of Kollidon® VA 64 Hot-Melt Extrudates

Cited by 32 publications

References 22 publications

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

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

Investigation of the combined effect of MgO and PEG on the release profile of mefenamic acid prepared via hot-melt extrusion techniques

Dissolution Enhancement in Cocoa Extract, Combining Hydrophilic Polymers through Hot-Melt Extrusion

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