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 Development and Evaluation of Amorphous Oral Thin Films Using Solvent-Free Processes: Comparison between 3D Printing and Hot-Melt Extrusion Technologies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1613
Author(s):  
Jiaxiang Zhang ◽  
Anqi Lu ◽  
Rishi Thakkar ◽  
Yu Zhang ◽  
Mohammed Maniruzzaman
Keyword(s):  
Thin Films ◽  
3D Printing ◽  
Drug Release ◽  
Hot Melt Extrusion ◽  
Dosage Forms ◽  
Solvent Free ◽  
Melt Extrusion ◽  
Physico Chemical ◽  
3D Printed ◽  
Hot Melt

Conventional oral dosage forms may not always be optimal especially for those patients suffering from dysphasia or difficulty swallowing. Development of suitable oral thin films (OTFs), therefore, can be an excellent alternative to conventional dosage forms for these patient groups. Hence, the main objective of the current investigation is to develop oral thin film (OTF) formulations using novel solvent-free approaches, including additive manufacturing (AM), hot-melt extrusion, and melt casting. AM, popularly recognized as 3D printing, has been widely utilized for on-demand and personalized formulation development in the pharmaceutical industry. Additionally, in general active pharmaceutical ingredients (APIs) are dissolved or dispersed in polymeric matrices to form amorphous solid dispersions (ASDs). In this study, acetaminophen (APAP) was selected as the model drug, and Klucel™ hydroxypropyl cellulose (HPC) E5 and Soluplus® were used as carrier matrices to form the OTFs. Amorphous OTFs were successfully manufactured by hot-melt extrusion and 3D printing technologies followed by comprehensive studies on the physico-chemical properties of the drug and developed OTFs. Advanced physico-chemical characterizations revealed the presence of amorphous drug in both HME and 3D printed films whereas some crystalline traces were visible in solvent and melt cast films. Moreover, advanced surface analysis conducted by Raman mapping confirmed a more homogenous distribution of amorphous drugs in 3D printed films compared to those prepared by other methods. A series of mathematical models were also used to describe drug release mechanisms from the developed OTFs. Moreover, the in vitro dissolution studies of the 3D printed films demonstrated an improved drug release performance compared to the melt cast or extruded films. This study suggested that HME combined with 3D printing can potentially improve the physical properties of formulations and produce OTFs with preferred qualities such as faster dissolution rate of drugs.

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

Ethylene vinyl acetate as matrix for oral sustained release dosage forms produced via hot-melt extrusion

2011 ◽  
Vol 77 (2) ◽  
pp. 297-305 ◽  
Author(s):  
A. Almeida ◽  
S. Possemiers ◽  
M.N. Boone ◽  
T. De Beer ◽  
T. Quinten ◽  
...  
Keyword(s):  
Sustained Release ◽  
Vinyl Acetate ◽  
Ethylene Vinyl Acetate ◽  
Hot Melt Extrusion ◽  
Dosage Forms ◽  
Melt Extrusion ◽  
Hot Melt

scholarly journals Impact of Drug Loading Method on Drug Release from 3D-Printed Tablets Made from Filaments Fabricated by Hot-Melt Extrusion and Impregnation Processes

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1607
Author(s):  
Kasitpong Thanawuth ◽  
Lalinthip Sutthapitaksakul ◽  
Srisuda Konthong ◽  
Supakij Suttiruengwong ◽  
Kampanart Huanbutta ◽  
...  
Keyword(s):  
Drug Release ◽  
Drug Loading ◽  
Hot Melt Extrusion ◽  
Water Soluble ◽  
Melt Extrusion ◽  
Drug Content ◽  
Loading Method ◽  
Lower Drug ◽  
3D Printed ◽  
Hot Melt

The purpose of this study was to investigate the impact of the drug loading method on drug release from 3D-printed tablets. Filaments comprising a poorly water-soluble model drug, indomethacin (IND), and a polymer, polyvinyl alcohol (PVA), were prepared by hot-melt extrusion (HME) and compared with IND-loaded filaments prepared with an impregnation (IMP) process. The 3D-printed tablets were fabricated using a fused deposition modeling 3D printer. The filaments and 3D printed tablets were evaluated for their physicochemical properties, swelling and matrix erosion behaviors, drug content, and drug release. Physicochemical investigations revealed no drug–excipient interaction or degradation. IND-loaded PVA filaments produced by IMP had a low drug content and a rapid drug release. Filaments produced by HME with a lower drug content released the drug faster than those with a higher drug content. The drug content and drug release of 3D-printed tablets containing IND were similar to those of the filament results. Particularly, drug release was faster in 3D-printed tablets produced with filaments with lower drug content (both by IMP and HME). The drug release of 3D-printed tablets produced from HME filaments with higher drug content was extended to 24 h due to a swelling-erosion process. This study confirmed that the drug loading method has a substantial influence on drug content, which in turn has a significant effect on drug release. The results suggest that increasing the drug content in filaments might delay drug release from 3D-printed tablets, which may be used for developing dosage forms suited for personalized medicine.

scholarly journals Hot-melt extrusion and prilling as contemporary and promising techniques in the solvent free production of solid oral dosage forms, based on solid dispersions

2016 ◽  
Vol 62 (1) ◽  
pp. 3-24 ◽  
Author(s):  
Aleksandar Aleksovski ◽  
Chris Vervaet ◽  
Rok Dreu
Keyword(s):  
Drug Delivery ◽  
Hot Melt Extrusion ◽  
Dosage Forms ◽  
Solvent Free ◽  
Oral Dosage ◽  
Drug Dissolution ◽  
Melt Extrusion ◽  
Solid Oral Dosage Forms ◽  
Oral Dosage Forms ◽  
Hot Melt

Hot melt extrusion and prilling are gaining importance as solvent free and continuous techniques in the production of solid oral dosage forms with added value, by incorporating active compound in a molten carrier which is further solidified to form solid dispersion. This article reviews these two techniques in terms of understanding process basics, equipment characteristics, required properties of processed materials and application of the processes for development of solid oral dosage forms. Studies revealed that both hot-melt extrusion and prilling are regarded as simple, robust and continuous methods for processing different types of materials and production of solid dosage forms based on solid matrices. However, understanding of their concepts and requirements together with careful material selection is crucial for stable material processing and obtaining stable products of high-quality. Hot-melt extrusion proved to be a suitable method for production of modified release dosage forms, taste masked dosage forms and dosage forms offering improved drug dissolution rate and solubility. Prilling till now has been successfully applied just in the production of multiple unit drug delivery systems for immediate and sustained drug delivery. Further studies on product development and process understanding are required for full implementation of prilling in the pharmaceutical field.

scholarly journals HOT MELT EXTRUSION IN ENGINEERING OF DRUG COCRYSTALS: A REVIEW

2021 ◽  
pp. 10-19
Author(s):  
ARCHANA RAJADHYAX ◽  
UJWALA SHINDE ◽  
HARITA DESAI ◽  
SHRUSHTI MANE
Keyword(s):  
Crystal Engineering ◽  
Process Analytical Technology ◽  
Hot Melt Extrusion ◽  
Dosage Forms ◽  
Solvent Free ◽  
Water Soluble ◽  
Melt Extrusion ◽  
Pharmaceutical Dosage Forms ◽  
Free Process ◽  
Hot Melt

Crystal engineering technique has been widely explored in recent times to bring about changes in crystallinity which aids to achieve various goals such as solubility enhancement, stability and in vivo bioavailability without altering the chemical properties of the drug. Cocrystallisation is one of the crystal engineering approaches where the drug and an inert coformer are linked together by hydrogen bonding forming supramolecular homosynthon or heterosynthon using solvent-based or solvent-free techniques. Processing of active pharmaceutical ingredients with inert water-soluble coformers yields multicomponent crystalline cocrystals with high-performance characteristics and enhanced flow properties. Due to the emerging need of the industry for greener techniques, hot melt extrusion (HME), a continuous and solvent-free process is emerging as a field of interest in the mechanochemical synthesis of various pharmaceutical dosage forms such as solid dispersions, implants, ointments, and cocrystals. The current review emphasizes the role of HME as a cocrystallization technique for drugs to tailor-make their properties and ease of formulation. The distinct feature of HME is phase control during the process of cocrystallization. Furthermore, the selection of appropriate coformers with desirable water-solubility and stability features makes HME amenable to cocrystallization of versatile actives yielding suitable dosage forms. The application of process analytical technology further adds ease of monitoring during HME in cocrystallization approaches. Due to these salient features of HME, it can act as a prospective technique for cocrystallization of versatile drugs thus yielding dosage forms with desirable solubility and stability features.

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