scholarly journals Vacuum Compression Molding as a Screening Tool to Investigate Carrier Suitability for Hot-Melt Extrusion Formulations

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1019
Author(s):  
Gauri Shadambikar ◽  
Thomas Kipping ◽  
Nicole Di-Gallo ◽  
Alessandro-Giuseppe Elia ◽  
Anja-Nadine Knüttel ◽  
...  
Keyword(s):  
Screening Tool ◽  
Drug Carriers ◽  
Hot Melt Extrusion ◽  
Compression Molding ◽  
Simulated Gastric Fluid ◽  
Formulation Development ◽  
Melt Extrusion ◽  
Scanning Calorimetry ◽  
Production Scale ◽  
Hot Melt

Hot-melt extrusion (HME) is the most preferred and effective method for manufacturing amorphous solid dispersions at production scale, but it consumes large amounts of samples when used for formulation development. Herein, we show a novel approach to screen the polymers by overcoming the disadvantage of conventional HME screening by using a minimum quantity of active pharmaceutical ingredient (API). Vacuum Compression Molding (VCM) is a fusion-based method to form solid specimens starting from powders. This study aimed to investigate the processability of VCM for the creation of amorphous formulations and to compare its results with HME-processed formulations. Mixtures of indomethacin (IND) with drug carriers (Parteck® MXP, Soluplus®, Kollidon® VA 64, Eudragit® EPO) were processed using VCM and extrusion technology. Thermal characterization was performed using differential scanning calorimetry, and the solid-state was analyzed via X-ray powder diffraction. Dissolution studies in the simulated gastric fluid were performed to evaluate the drug release. Both technologies showed similar results proving the effectiveness of VCM as a screening tool for HME-based formulations.

Fabrication of Indomethacin-Loaded Polyvinyl Alcohol Filaments through Hot-Melt Extrusion

2020 ◽  
Vol 859 ◽  
pp. 247-251
Author(s):  
Kasitpong Thanawuth ◽  
Pornsak Sriamornsak
Keyword(s):  
Polyvinyl Alcohol ◽  
Drug Loading ◽  
Analysis Data ◽  
Hot Melt Extrusion ◽  
Extrusion Process ◽  
Melt Extrusion ◽  
Scanning Calorimetry ◽  
Yellow Color ◽  
Model Drug ◽  
Hot Melt

The main objective of this study was to prepare the drug-loaded filament by hot-melt extrusion technique. Indomethacin (IND) was used as a model drug and polyvinyl alcohol (PVA) was used to produce the filament. The IND-PVA filament had clear yellow color and rough surface. Drug loading in the filament that was determined from three segments of the filament was similar, indicating that IND was homogeneously distributed in the filament.This finding was confirmed by differential scanning calorimetry and powder X-ray diffraction. In addition, thermogravimetric analysis data suggested that the drug and polymer were not degraded at temperature used in extrusion process. The filament could be further developed as dosage form or applied as starting material for 3D-printed dosage forms.

Application of Hot Melt Extrusion Technology in the Development of Abuse Deterrent Formulations: An Overview

2020 ◽  
Vol 17 ◽  
Author(s):  
Arun Butreddy ◽  
Dinesh Nyavanandi ◽  
Sagar Narala ◽  
Fischer Austin ◽  
Suresh Bandari
Keyword(s):  
Chronic Pain ◽  
Opioid Analgesic ◽  
Hot Melt Extrusion ◽  
Matrix Tablets ◽  
Health Concern ◽  
Prescription Opioid ◽  
Pharmaceutical Companies ◽  
Formulation Development ◽  
Melt Extrusion ◽  
Hot Melt

: The misuse, abuse, and illicit use of prescription opioid analgesics is a global public health concern. However, there are many viable therapeutic options for the treatment of patients with chronic pain. Both intact and manipulated opioid drug products are abused by various routes such as oral, nasal, and injection which may lead to overdose, drug addiction, and even death. To combat the abuse of these medications, regulatory agencies and pharmaceutical companies are switching their interest towards developing Abuse deterrent formulations (ADFs), with the intent to deter the abuse of opioid products to a maximum extent. Thereare several manufacturing strategies implemented in an attempt to develop ADFs. An example include matrix tablets of high molecular weight polymers such as polyethylene oxide. The scalable and continuous manufacturing techniques, such as hot melt extrusion (HME), is increasingly accepted by pharmaceutical companies to advance the development and manufacturing of ADFs. The application of the HME technique in the development of ADFs may overcome the challenges of opioid analgesic formulation development and provide improved protection against misuse and abuse, while also ensuring access to safe and effective use in patients with chronic pain. This review deals with a briefoverview of strategies, with emphasis on HME to deter opioid abuse, in vitrocharacterization methods, commonly used excipients in the development of ADFs, and regulatory standards to meet the requirements of ADFs.

scholarly journals Formulation and Characterization of Solid Dispersion Prepared by Hot Melt Mixing: A Fast Screening Approach for Polymer Selection

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Arno A. Enose ◽  
Priya K. Dasan ◽  
H. Sivaramakrishnan ◽  
Sanket M. Shah
Keyword(s):  
Solid Dispersion ◽  
Hot Melt Extrusion ◽  
Extrusion Process ◽  
Melt Extrusion ◽  
Dynamic Vapor Sorption ◽  
Scanning Calorimetry ◽  
Melt Mixing ◽  
Predictive Tool ◽  
Evaporation Technique ◽  
Hot Melt

Solid dispersion is molecular dispersion of drug in a polymer matrix which leads to improved solubility and hence better bioavailability. Solvent evaporation technique was employed to prepare films of different combinations of polymers, plasticizer, and a modal drug sulindac to narrow down on a few polymer-plasticizer-sulindac combinations. The sulindac-polymer-plasticizer combination that was stable with good film forming properties was processed by hot melt mixing, a technique close to hot melt extrusion, to predict its behavior in a hot melt extrusion process. Hot melt mixing is not a substitute to hot melt extrusion but is an aid in predicting the formation of molecularly dispersed form of a given set of drug-polymer-plasticizer combination in a hot melt extrusion process. The formulations were characterized by advanced techniques like optical microscopy, differential scanning calorimetry, hot stage microscopy, dynamic vapor sorption, and X-ray diffraction. Subsequently, the best drug-polymer-plasticizer combination obtained by hot melt mixing was subjected to hot melt extrusion process to validate the usefulness of hot melt mixing as a predictive tool in hot melt extrusion process.

scholarly journals IMPROVING SOLUBILITY AND DISSOLUTION OF A NATURAL PRODUCT APIGENIN VIA PREPARATION OF SOLID DISPERSION BY HOT MELT EXTRUSION

2021 ◽  
pp. 47-52
Author(s):  
SOFI N. STIANI ◽  
TAOFIK RUSDIANA ◽  
ANAS SUBARNAS
Keyword(s):  
Solid Dispersion ◽  
Water Solubility ◽  
Practical Method ◽  
Hot Melt Extrusion ◽  
Raw Material ◽  
Melt Extrusion ◽  
Scanning Calorimetry ◽  
Twin Screw ◽  
Hot Melt

Objective: Hot Melt Extrusion (HME) is one of the techniques for preparing a solid dispersion hydrophilic excipient known as a no solvents practical method to increase the solubility of drugs. Apigenin (APG) has properties that thermal stable with melting point 345-350 °C but very low solubility in the water around 1,35 µg/ml. The polymer is stable in the HME method are Soluplus and Kollidon VA 64. The study aims to optimize the kind of polymer in HME formulae to improve the solubility and dissolution rate of apigenin by solid dispersion using hot-melt extrusion. Methods: Apigenin 10–50% w/w and Kollidon®VA 64 or Soluplus® and combination of Kollidon®VA 64 and Soluplus® were mixed, and the resulting blends extruded using a twin-screw extruder (Teach-Line ZK25T). Characterization of apigenin extrudates conducted using scanning electron microscopy, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, powder X-ray diffractometry, and dissolution. Results: Solubility studies presented enhancement in apigenin of 10%/Soluplus®90%; 10% w/w apigenin/Kollidon®VA 64 (90%); and 33,3% w/w apigenin/Kollidon®VA 64 33,3% mix Soluplus® 33,3% increased more than 18,25; 16,18-and 8,52-fold in water, respectively. Furthermore dissolution studies showed enhancement in apigenin percent release of 10%/Soluplus®90%; 10% w/w apigenin/Kollidon®VA 64 90%; and 33,3% w/w apigenin/Kollidon®VA 64 33,3% mix Soluplus® 33,3% tablet apigenin HME up to 34,29%; 69,75% and 30,69%, respectively. Conclusion: The formulation of 10% w/w Apigenin and 90% Soluplus® using hot-melt extrusion able to increase water solubility approximately 18,25-fold than raw material apigenin.

scholarly journals Preparation of Curcumin-Eudragit® E PO Solid Dispersions with Gradient Temperature through Hot-Melt Extrusion

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4964
Author(s):  
Wenling Fan ◽  
Xiaotong Zhang ◽  
Wenjing Zhu ◽  
Xinyi Zhang ◽  
Liuqing Di
Keyword(s):  
Solid Dispersions ◽  
Hot Melt Extrusion ◽  
Solubility Parameters ◽  
Sprague Dawley ◽  
Melt Extrusion ◽  
Scanning Calorimetry ◽  
In Vivo Experiments ◽  
Hot Melt

Hot-melt extrusion (HME) has great advantages for the preparation of solid dispersion (SD), for instance, it does not require any organic solvents. Nevertheless, its application to high-melting-point and thermosensitive drugs has been rarely reported. In this study, thermally unstable curcumin (Cur) was used as a drug model. The HME process was systematically studied by adjusting the gradient temperature mode and residence time, with the content, crystallinity and dissolution of Cur as the investigated factors. The effects of barrel temperature, screw speed and cooling rate on HME were also examined. Solubility parameters and the Flory–Huggins method were used to evaluate the miscibility between Cur and carriers. Differential scanning calorimetry, X-ray diffraction, Fourier transform infrared spectroscopy, equilibrium solubility and in vitro and in vivo experiments were used to characterize and evaluate the results. An amorphous Cur SD was successfully obtained, increasing the solubility and release of Cur. In the optimal process, the mass ratio of Cur to Eudragit® E PO (EPO) was 1:4 and the barrel temperature was set at a gradient heating mode (130 °C–135 °C–140 °C–145 °C–150 °C–155 °C–160 °C) at 100 rpm. Related pharmacokinetic test results also showed the improved bioavailability of the drug in rats. In a pharmacodynamic analysis of Sprague–Dawley rats, the Cmax and the bioavailability of the Cur-EPO SD were 2.6 and 1.5 times higher than those of Cur, respectively. The preparation of the amorphous SD not only provided more solubility but also improved the bioavailability of Cur, which provides an effective way to improve the bioavailability of BCS II drugs.

Dissolution improvement of an active pharmaceutical ingredient in a polymer melt by hot melt extrusion

2019 ◽  
Vol 39 (2) ◽  
pp. 186-196 ◽  
Author(s):  
Laura Restrepo-Uribe ◽  
Nicolas Ioannidis ◽  
Maria del Pilar Noriega
Keyword(s):  
Solid Dispersions ◽  
Amorphous Solid ◽  
Hot Melt Extrusion ◽  
Release Profile ◽  
Operating Conditions ◽  
Water Soluble ◽  
Melt Extrusion ◽  
Scanning Calorimetry ◽  
Screening Process ◽  
Hot Melt

Abstract Dissolution of poorly water-soluble active pharmaceutical ingredients (APIs) in polymeric melts plays an important role in the manufacturing of solid dispersions and solid solutions. The understanding of the dissolution is essential for selecting the processing equipment, the operating conditions, and the polymer excipients. The methodology presented in this work for ketoprofen (KTO) and polymer excipients serves as a screening process to select the best API-polymer formulation for hot melt extrusion (HME) to target a specific release profile. KTO dispersion within the polymer was characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), and dissolution tests. Thermal characterization shows that a single phase amorphous solid solution (one glass transition temperature [Tg]) was achieved under the HME processing conditions and screw configuration; and with the combination of polymer excipients, an extended release profile of KTO was accomplished, releasing 100% of KTO in 24 h.

scholarly journals Preliminary Development of Solid Dispersion for an Insoluble Compound ZL006 by Miniaturized Hot Melt Extrusion

2019 ◽  
Vol 01 (01) ◽  
pp. e11-e21
Author(s):  
Lijun Zhang ◽  
Hansen Luan ◽  
Weiyue Lu ◽  
Hao Wang
Keyword(s):  
Solid Dispersion ◽  
Scale Up ◽  
Hot Melt Extrusion ◽  
Minimal Amount ◽  
Melt Extrusion ◽  
Scanning Calorimetry ◽  
Modulated Differential Scanning Calorimetry ◽  
Hydrogen Bond Formation ◽  
Hot Melt

AbstractThe purpose of this study was to develop a solid dispersion (SD) by miniaturized hot-melt extrusion (HME) for an insoluble molecule ZL006 which showed potency of increasing leukocytes. A preliminary formulation screening was conducted using solvent evaporation method. The selected SD formulation was further optimized and scaled up using a miniaturized twin-screw extruder. Solid-state characterizations of the scale-up SD and its corresponding physical mixture (PM) were performed by X-ray powder diffraction (XRPD), modulated differential scanning calorimetry (mDSC), and Fourier's transform infrared spectroscopy (FTIR). XRPD and mDSC results indicated the formation of amorphous SD. FTIR spectrum indicated the possible hydrogen bond formation between the compound and the excipient. A discriminating non-sink condition micro-dissolution of SD showed the fast release of ZL006 which was approximately two-fold and three-fold of dissolution of PM and pure crystalline compound, respectively. The preliminary in vivo pharmacokinetics (PK) study in rats showed 71% oral bioavailability from the SD, while the bioavailability of ZL006 conventional suspension was less than 1%. Thus, an SD formulation for ZL006 with improved solubility and bioavailability was developed by miniaturized HME with minimal amount of compound at early preclinical stage, which could enable the preclinical evaluation.

Sign in / Sign up

Export Citation Format

Share Document