Processing thermally labile drugs by hot-melt extrusion: The lesson with gliclazide

Huang, Siyuan; O’Donnell, K. P.; Vaux, Sophie M. Delpon de; O’Brien, John P.; Stutzman, John R.; Williams, Robert O.

doi:10.1016/j.ejpb.2017.05.014

Cited by 72 publications

(47 citation statements)

References 46 publications

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“…SD and HME are techniques that may be employed to produce FDCs, with both techniques having their own associated advantages and disadvantages. Thermal (and mechanical) energy input during the extrusion process is normally supplied via heat conduction from barrel heating zones and the friction of the melt against the screw elements and interior wall of the extruder barrel (Huang et al, 2017). It is because of this heat conduction that degradation of thermolabile compounds can arise.…”

Section: Introductionmentioning

confidence: 99%

A comparative study between hot-melt extrusion and spray-drying for the manufacture of anti-hypertension compatible monolithic fixed-dose combination products

Kelleher

Gilvary

Madi

et al. 2018

International Journal of Pharmaceutics

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The purpose of this work was to investigate the application of different advanced continuous processing techniques (hot melt extrusion and spray drying) to the production of fixed-dose combination (FDC) monolithic systems comprising of hydrochlorothiazide and ramipril for the treatment of hypertension. Identical FDC formulations were manufactured by the two different methods and were characterised using powder X-ray diffraction (PXRD) and modulated differential scanning calorimetry (mDSC). Drug dissolution rates were investigated using a Wood's apparatus, while physical stability was assessed on storage under controlled temperature and humidity conditions. Interestingly both drugs were transformed into their amorphous forms when spray dried, however, hydrochlorothiazide was determined, by PXRD, to be partially crystalline when hot melt extruded with either polymer carrier (Kollidon® VA 64 or Soluplus®). Hot melt extrusion was found to result in significant degradation of ramipril, however, this could be mitigated by the inclusion of the plasticizer, polyethylene glycol 3350, in the formulation and appropriate adjustment of processing temperature. The results of intrinsic dissolution rate studies showed that hot-melt extruded samples were found to release both drugs faster than identical formulations produced via spray drying. However, the differences were attributable to the surface roughness of the compressed discs in the Wood's apparatus, rather than solid state differences between samples. After a 60-day stability study spray dried samples exhibited a greater physical stability than the equivalent hot melt extruded samples.

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Section: Introductionmentioning

confidence: 99%

A comparative study between hot-melt extrusion and spray-drying for the manufacture of anti-hypertension compatible monolithic fixed-dose combination products

Kelleher

Gilvary

Madi

et al. 2018

International Journal of Pharmaceutics

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“…Solid dispersions equivalent to 150 mg of Ivacaftor were weighed accurately and dissolved in 100 ml of 0.1% trifluoroacetic acid: acetonitrile (20:80 ratio). The solution was filtered and diluted with the suitable amount, and drug content was analyzed at ë max 255 nm against blank using UV spectrometer [8]. The actual drug content was calculated using the following equation:…”

Section: Drug Contentmentioning

confidence: 99%

Solubility and Dissolution Enhancement of Ivacaftor Tablets by Using Solid Dispersion Technique of Hot-Melt Extrusion - A Design of Experimental Approach

Guntaka

Srinivas

2019

Asian J Pharm Clin Res

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Objective: The objective was to improve the solubility and dissolution of ivacaftor tablets by using solid dispersion (SD) technique.Methods: Ivacaftor is practically insoluble (<0.001 mg/mL) over pH value of 3.0–7.5 due to low solubility, and it shows poor bioavailability after oral administration. Therefore, SDs of Ivacaftor were prepared by SD technique of hot-melt extrusion (HME) by adding different polymers such as Soluplus, Hypromellose 5 cps, and Copovidone with surfactants sodium lauryl sulfate, poloxamer, and polysorbate 80 to enhance its solubility.Results: After the analysis of Fourier-transform infrared spectrometry, X-ray diffraction, and differential scanning calorimetry of SDs by HME shows a converted in crystalline structure form to an amorphous structure form of Ivacaftor. The results show that the formulation of Ivacaftor SDs by HMT has enhanced the solubility and dissolution of Ivacaftor.Conclusion: In the present study, the SDs of the poorly soluble drug substance Ivacaftor were successfully prepared using HME. The in vitro dissolution test shows a significant increase in dissolution rate of SDs prepared by HME (95%) in formulation FHM8 compared with plain Ivacaftor (9%) within 30 min.

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“…Stability studies carried out according to the Arrhenius equation on the different extruded batches indicated two hydrolysis degradation pathways of gliclazide, while the activation energy results indicated that gliclazide in the amorphous form had a much higher degradation rate than it did in the crystalline one. The authors were able to reduce the chemical degradation by changing and optimizing the process, in particular, by reducing the stress forces [ 58 ].…”

Section: Introductionmentioning

confidence: 99%

“…This information was key for optimizing the HME process. The authors were able to use a lower processing temperature, far below the degradation temperature, based on their findings that the gliclazite and Affinisol™ exhibit good miscibility, and that the solubilization of the drug in this polymer serves as a plasticizer [ 58 ].…”

Section: Introductionmentioning

confidence: 99%

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Hot Melt Extrusion: Highlighting Physicochemical Factors to Be Investigated While Designing and Optimizing a Hot Melt Extrusion Process

et al. 2018

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Hot-melt extrusion (HME) is a well-accepted and extensively studied method for preparing numerous types of drug delivery systems and dosage forms. It offers several advantages: no solvents are required, it is easy to scale up and employ on the industrial level, and, in particular, it offers the possibility of improving drug bioavailability. HME involves the mixing of a drug with one or more excipients, in general polymers and even plasticizers, which can melt, often forming a solid dispersion of the drug in the polymer. The molten mass is extruded and cooled, giving rise to a solid material with designed properties. This process, which can be realized using different kinds of special equipment, may involve modifications in the drug physicochemical properties, such as chemical, thermal and mechanical characteristics thus affecting the drug physicochemical stability and bioavailability. During process optimization, the evaluation of the drug solid state and stability is thus of paramount importance to guarantee stable drug properties for the duration of the drug product shelf life. This manuscript reviews the most important physicochemical factors that should be investigated while designing and optimizing a hot melt extrusion process, and by extension, during the different pre-formulation, formulation and process, and post-formulation phases. It offers a comprehensive evaluation of the chemical and thermal stability of extrudates, the solid physical state of extrudates, possible drug-polymer interactions, the miscibility/solubility of the drug-polymer system, the rheological properties of extrudates, the physicomechanical properties of films produced by hot melt extrusion, and drug particle dissolution from extrudates. It draws upon the last ten years of research, extending inquiry as broadly as possible.

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Processing thermally labile drugs by hot-melt extrusion: The lesson with gliclazide

Cited by 72 publications

References 46 publications

A comparative study between hot-melt extrusion and spray-drying for the manufacture of anti-hypertension compatible monolithic fixed-dose combination products

A comparative study between hot-melt extrusion and spray-drying for the manufacture of anti-hypertension compatible monolithic fixed-dose combination products

Solubility and Dissolution Enhancement of Ivacaftor Tablets by Using Solid Dispersion Technique of Hot-Melt Extrusion - A Design of Experimental Approach

Hot Melt Extrusion: Highlighting Physicochemical Factors to Be Investigated While Designing and Optimizing a Hot Melt Extrusion Process

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