Continuous low-dose feeding of highly active pharmaceutical ingredients in hot-melt extrusion

Preparation of amorphous solid dispersions (ASD) by hot melt extrusion (HME) of poly(vinylpyrrolidone-vinyl acetate) (Kollidon) and the active pharmaceutical ingredients (API) Lamivudine (3TC) and Tenofovir Disoproxyl Fumarate (TDF) was investigated aiming to study their miscibility and thermal behavior. These two drugs are currently used as drugs in first line treatment of patients with Acquired Immunodeficiency Syndrome (AIDS). In order to predetermine parameters for extrusion and the maximum concentration of API to be used without any recrystallization, binary blends were first processed in the mixing chamber at 130°C using a roller type rotor at 10, 20 and 30 rpm for 7 min, giving rise to ASD of both API, at least up to 20 wt% of the drug. Both 3TC and TDF were then extruded individually with Kollidon in a single screw extruder. HME produced ASD with high concentration of both Kollidon/API combinations, being part of the API soluble in the polymer matrix. From HME, Kollidon/3TC forms ASD in concentration up to 50 wt%, but from 30 wt% 3TC, the ASD has no time stability, showing recrystallization in less than 5 months, while the Kollidon/TDF system forms ASD up to 30 wt% of TDF, but it has aging stability inferior to 4 months.

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Opportunities for Successful Stabilization of Poor Glass-Forming Drugs: A Stability-Based Comparison of Mesoporous Silica Versus Hot Melt Extrusion Technologies

Pharmaceutics ◽

10.3390/pharmaceutics11110577 ◽

2019 ◽

Vol 11 (11) ◽

pp. 577 ◽

Cited By ~ 2

Author(s):

Felix Ditzinger ◽

Daniel J. Price ◽

Anita Nair ◽

Johanna Becker-Baldus ◽

Clemens Glaubitz ◽

...

Keyword(s):

Solid State ◽

Mesoporous Silica ◽

Oral Absorption ◽

Hot Melt Extrusion ◽

Resonance Spectroscopy ◽

Melt Extrusion ◽

Pharmaceutical Ingredients ◽

Poorly Soluble ◽

Co Precipitation ◽

Hot Melt

Amorphous formulation technologies to improve oral absorption of poorly soluble active pharmaceutical ingredients (APIs) have become increasingly prevalent. Currently, polymer-based amorphous formulations manufactured by spray drying, hot melt extrusion (HME), or co-precipitation are most common. However, these technologies have challenges in terms of the successful stabilization of poor glass former compounds in the amorphous form. An alternative approach is mesoporous silica, which stabilizes APIs in non-crystalline form via molecular adsorption inside nano-scale pores. In line with these considerations, two poor glass formers, haloperidol and carbamazepine, were formulated as polymer-based solid dispersion via HME and with mesoporous silica, and their stability was compared under accelerated conditions. Changes were monitored over three months with respect to solid-state form and dissolution. The results were supported by solid-state nuclear magnetic resonance spectroscopy (SS-NMR) and scanning electron microscopy (SEM). It was demonstrated that mesoporous silica was more successful than HME in the stabilization of the selected poor glass formers. While both drugs remained non-crystalline during the study using mesoporous silica, polymer-based HME formulations showed recrystallization after one week. Thus, mesoporous silica represents an attractive technology to extend the formulation toolbox to poorly soluble poor glass formers.

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Review on Hot Melt Extrusion Technology and it's Application

International Journal of Scientific Research in Science and Technology ◽

10.32628/ijsrst196653 ◽

2019 ◽

pp. 253-260

Author(s):

Mali A. S. ◽

Gavali K. V. ◽

Choudhari R. G. ◽

Anekar V. P. ◽

Gavhane Y. N.

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Hot Melt Extrusion ◽

Delivery Systems ◽

Taste Masking ◽

Melt Extrusion ◽

Pharmaceutical Ingredients ◽

Pharmaceutical Industries ◽

Extrusion Technology ◽

Hot Melt

The use of hot-melt extrusion (HME) within the pharmaceutical industry is steadily increasing, due to proven its ability to efficiently manufacture novel products. With the use of HME we can increase solubility and bioavailability of the API. HME has proven to be a robust method of producing numerous drug delivery systems like modified, controlled and targeted drug delivery systems. resulting improved bioavailability as well as taste masking of bitter active pharmaceutical ingredients (APIs). Hot-melt extrusion techniques are pragmatic in the manufacture of a variety of dosage forms and formulations such as granules, pellets, tablets, suppositories, implants, stents, transdermal systems and ophthalmic inserts. In This paper we review about the types of Extruder, solid dispersion and Application of the HME to the pharmaceutical industries.

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