scholarly journals Hot Melt Extrusion Processing Parameters Optimization

Processes ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 1516
Author(s):  
Abdullah Alshetaili ◽  
Saad M. Alshahrani ◽  
Bjad K. Almutairy ◽  
Michael A. Repka
Keyword(s):  
Factorial Design ◽  
Processing Parameters ◽  
Hot Melt Extrusion ◽  
Parameters Optimization ◽  
Extrusion Temperature ◽  
In Vitro Dissolution ◽  
Dissolution Profile ◽  
Melt Extrusion ◽  
The Impact ◽  
Hot Melt

The aim of this study was to demonstrate the impact of processing parameters of the hot-melt extrusion (HME) on the pharmaceutical formulation properties. Carbamazepine (CBZ) was selected as a model water-insoluble drug. It was incorporated into Soluplus®, which was used as the polymeric carrier, to produce a solid dispersion model system. The following HME-independent parameters were investigated at different levels: extrusion temperature, screw speed and screw configuration. Design of experiment (DOE) concept was applied to find the most significant factor with minimum numbers of experimental runs. A full two-level factorial design was applied to assess the main effects, parameter interactions and total error. The extrudates’ CBZ content and the in vitro dissolution rate were selected as response variables. Material properties, including melting point, glass transition, and thermal stability, and polymorphs changes were used to set the processing range. In addition, the extruder torque and pressure were used to find the simplest DOE model. Each change of the parameter showed a unique pattern of dissolution profile, indicating that processing parameters have an influence on formulation properties. A simple, novel and two-level factorial design was able to evaluate each parameter effect and find the optimized formulation. Screw configuration and extrusion temperature were the most affecting parameters in this study.

scholarly journals Influence of Carbamazepine Dihydrate on the Preparation of Amorphous Solid Dispersions by Hot Melt Extrusion

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 379 ◽  
Author(s):  
Xiangyu Ma ◽  
Felix Müller ◽  
Siyuan Huang ◽  
Michael Lowinger ◽  
Xu Liu ◽  
...  
Keyword(s):  
Energy State ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Hot Melt Extrusion ◽  
Water Soluble ◽  
Melt Extrusion ◽  
Amorphous Solid Dispersions ◽  
Water Soluble Drugs ◽  
The Impact ◽  
Hot Melt

Amorphous solid dispersions (ASDs) are commonly used in the pharmaceutical industry to improve the dissolution and bioavailability of poorly water-soluble drugs. Hot melt extrusion (HME) has been employed to prepare ASD based products. However, due to the narrow processing window of HME, ASDs are normally obtained with high processing temperatures and mechanical stress. Interestingly, one-third of pharmaceutical compounds reportedly exist in hydrate forms. In this study, we selected carbamazepine (CBZ) dihydrate to investigate its solid-state changes during the dehydration process and the impact of the dehydration on the preparation of CBZ ASDs using a Leistritz micro-18 extruder. Various characterization techniques were used to study the dehydration kinetics of CBZ dihydrate under different conditions. We designed the extrusion runs and demonstrated that: 1) the dehydration of CBZ dihydrate resulted in a disordered state of the drug molecule; 2) the resulted higher energy state CBZ facilitated the drug solubilization and mixing with the polymer matrix during the HME process, which significantly decreased the required extrusion temperature from 140 to 60 °C for CBZ ASDs manufacturing compared to directly processing anhydrous crystalline CBZ. This work illustrated that the proper utilization of drug hydrates can significantly improve the processability of HME for preparing ASDs.

scholarly journals The impact of hot-melt extrusion on the tableting behaviour of polyvinyl alcohol

2016 ◽  
Vol 498 (1-2) ◽  
pp. 254-262 ◽  
Author(s):  
W. Grymonpré ◽  
W. De Jaeghere ◽  
E. Peeters ◽  
P. Adriaensens ◽  
J.P. Remon ◽  
...  
Keyword(s):  
Polyvinyl Alcohol ◽  
Hot Melt Extrusion ◽  
Melt Extrusion ◽  
The Impact ◽  
Hot Melt

scholarly journals SOLUBILITY AND DISSOLUTION ENHANCEMENT OF IVACAFTOR TABLETS BY USING SOLID DISPERSION TECHNIQUE OF HOT-MELT EXTRUSION - A DESIGN OF EXPERIMENTAL APPROACH

2019 ◽  
Vol 12 (1) ◽  
pp. 356
Author(s):  
Purnachandra Reddy Guntaka ◽  
Srinivas Lankalapalli
Keyword(s):  
Solid Dispersion ◽  
Ph Value ◽  
Hot Melt Extrusion ◽  
In Vitro Dissolution ◽  
Dissolution Enhancement ◽  
Infrared Spectrometry ◽  
Lauryl Sulfate ◽  
Melt Extrusion ◽  
Structure Form ◽  
Hot Melt

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.

scholarly journals Hot-Melt Extrusion Process Fluctuations and Their Impact on Critical Quality Attributes of Filaments and 3D-Printed Dosage Forms

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 511 ◽  
Author(s):  
Hanna Ponsar ◽  
Raphael Wiedey ◽  
Julian Quodbach
Keyword(s):  
Process Analysis ◽  
Hot Melt Extrusion ◽  
Quality Attributes ◽  
Dosage Forms ◽  
Melt Extrusion ◽  
Critical Quality Attributes ◽  
Filament Diameter ◽  
3D Printed ◽  
The Impact ◽  
Hot Melt

Fused deposition modeling (FDMTM) is a 3D-printing technology of rising interest for the manufacturing of customizable solid dosage forms. The coupling of hot-melt extrusion with FDMTM is favored to allow the production of pharma-grade filaments for the printing of medicines. Filament diameter consistency is a quality of great importance to ensure printability and content uniformity of 3D-printed drug delivery systems. A systematical process analysis referring to filament diameter variations has not been described in the literature. The presented study aimed at a process setup optimization and rational process analysis for filament fabrication related to influencing parameters on diameter inhomogeneity. In addition, the impact of diameter variation on the critical quality attributes of filaments (mechanical properties) and uniformity of mass of printed drug-free dosage forms was investigated. Process optimization by implementing a winder with a special haul-off unit was necessary to obtain reliable filament diameters. Subsequently, the optimized setup was used for conduction of rational extrusion analysis. The results revealed that an increased screw speed led to diameter fluctuations with a decisive influence on the mechanical resilience of filaments and mass uniformity of printed dosage forms. The specific feed load was identified as a key parameter for filament diameter consistency.

scholarly journals Enhancing the Cannabidiol (CBD) Compound in Formulated Hemp (Cannabis sativa L.) Leaves through the Application of Hot-Melt Extrusion

Processes ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 837
Author(s):  
Md Obyedul Kalam Azad ◽  
Byeong Ryeol Ryu ◽  
Md Soyel Rana ◽  
Md Hafizur Rahman ◽  
Jung-Dae Lim ◽  
...  
Keyword(s):  
Cannabis Sativa ◽  
Ascorbyl Palmitate ◽  
Processing Parameters ◽  
Hot Melt Extrusion ◽  
Total Phenolic ◽  
Flavonoid Content ◽  
Melt Extrusion ◽  
Food Industries ◽  
Cannabidiolic Acid ◽  
Hot Melt

Cannabidiol (CBD) is a non-psychoactive cannabinoid compound found in hemp plants that has recently sparked interest in the biomedical and food industries. CBD is a natural decarboxylated product of cannabidiolic acid (CBDA). In this study, processing parameters were developed to enhance the decarboxylation process of CBDA in hemp leaves using hot-melt extrusion (HME). The hemp leaves were formulated with two different acid-based polymers, namely ascorbic acid (AA) and ascorbyl palmitate (AP), before the HME. The results showed that the carboxylation process of CBDA was increased by at least 2.5 times in the extrudate leaves and the content of the CBD was four times higher when formulated with AP (2800 µg/g) compared with the raw leaves (736 µg/g). The total phenolic and total flavonoid content, as well as the DPPH antioxidant capacity, were higher in the AP formulated extrudate. At the same time, the Δ9-tetrahydrocannabinol (THC) content was reduced by half in the extrudate compared with the raw leaves. It was also observed that double HME processing did not increase the decarboxylation process. It was concluded that the HME process significantly improved the conversion rate of CBDA to CBD in formulated hemp leaves with a reduced THC content.

Fenofibrate Solid Dispersion Processed by Hot-Melt Extrusion: Elevated Bioavailability and Its Cell Transport Mechanism

2019 ◽  
Vol 16 (6) ◽  
pp. 538-547 ◽  
Author(s):  
Ting Wen ◽  
Boyi Niu ◽  
Qiaoli Wu ◽  
Yixian Zhou ◽  
Xin Pan ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Amorphous Solid ◽  
Hot Melt Extrusion ◽  
In Vitro Dissolution ◽  
Amorphous Solid Dispersion ◽  
Dissolution Test ◽  
Melt Extrusion ◽  
Cell Transport ◽  
Hot Melt

Background: Fenofibrate (FNB) is an effective drug for the treatment of hypertriglyceridemia, hypercholesterolemia as well as mixed hyperlipidemia. However, due to its poor aqueous solubility, FNB has the problem of poor oral absorption followed by low bioavailability. Objective: The aim of this research was to construct FNB amorphous solid dispersion employing PVP VA64 as the carrier by hot-melt extrusion method, in order to improve the oral bioavailability. Additionally, the cell transport experiment was conducted to further investigate the mechanism of promoted osmotic absorption. Methods: The physical state of the obtained solid dispersion was characterized using SEM, DSC and XRD. Besides, in vitro Caco-2 cells were used to evaluate the cytotoxicity of the carrier and mimic gastrointestinal drug permeation. At last, in vitro dissolution test and in vivo bioavailability study were also carried out. Results: The prepared FNB solid dispersion was found to be an amorphous state after hot-melt extrusion process. In vitro cytotoxicity test on Caco-2 cells confirmed the excellent biocompatibility of the carrier PVP VA64. Besides, transwell cell transport assay and in vitro dissolution test revealed that FNB released from amorphous solid dispersion was equipped with an improved transmembrane transport and dissolution rate. Moreover, pharmacokinetic study in beagle dogs showed that comparing with commercial micronized product Lipanthyl®, the oral bioavailability of FNB solid dispersion was significantly enhanced (2.45 fold). Conclusion: In conclusion, PVP VA64 can be regarded as a promising polymer to enhance the bioavailability of poorly water-soluble drugs such as FNB processed by hot-melt extrusion. Besides, investigations on the mechanism of the enhanced penetration are expected to lay a foundation on the subsequent development of effective and practical solid dispersion.

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