Hot-melt extrusion process

Generally, novel quick dissolving films are made by some of the established technologies like coating, solvent casting and hot-melt extrusion process. At first a wide web is produced and afterwards it will be cut into the desired size needed by the dosage form. 

Hot-melt extrusion has been approved as a solvent-free manufacturing process for ODFs. In this process, the API and other ingredients are mixed in a dry state, which is then subjected to a heating process and extruded out in a molten state. The blend of API, polymers 

---

Chokshi, R. J., H. K. Sandhu, R. M. Iyer, N. H. Shah, A. W. Malick, and H. Zia. 2005. Characterization of physico-mechanical properties of indomethacin and polymers to assess their suitability for hot-melt extrusion process as a means to manufacture solid dispersion/soJUflbarm ScB4 2463-2474. 

The design of the extrusion screw has a significant influence on the efficiency of the hot-melt extrusion process. The function of the screw is to transfer the material inside the barrel and then to mix, to compress, and to melt the polymeric materials and to pump the molten mass through the die. Several parameters are used to define the geometrical features of the screw (Fig. 2). 

Different types of downstream processing equipment are necessary for the hot-melt extrusion process. For extruded film preparations, chill rolls are used to cool down and control the film temperature before it is taken up by the roller. The thickness of the film can also be controlled by adjusting the rotating speed of the chill rolls. Control of the chill roll temperature... 

In addition to thermal degradation, the active compound may interfere with the functionality of the other components in the formulation. Oxprenolol hydrochloride was shown to melt under the hot-melt extrusion processing conditions, thus decreasing the... 

PEG 400, and potentially other plasticizers, to evaporate or degrade under hot-melt extrusion processing and storage. It is also evident that these findings for PEG 400 explain changes upon mechanical testing of PEG 400-incorporated HPC films. ... 

Another scale-up variable that can be easily controlled is the length to diameter ratio L/D). Scale-up with an equivalent L/D ratio is beneficial in avoiding non-linear scale-up issues, especially at production scale. Residence time distribution (RTD) is a useful term for understanding scale-up of hot-melt extrusion processing. The RTD is used to attempt to quantify the average amount of time a material spends in the processor. The RTD depends on screw speed, screw element design, and material characteristics. The preference during scale-up is to maintain an equivalent ... 

Hot-melt extrusion process In situ polymerization Interfacial cross-linking/reaction Interfacial polymerization Ionotropic gelation... 

Lyons, J.G. Hallinan, M. Kennedy, J.E. Devine, D.M. Geever, L.M. Blackie, P. Higginbotham, C.L. Preparation of monolithic matrices for oral drug delivery using a supercritical fluid assisted hot melt extrusion process. Int. J. Pharm. 2007,329(1-2), 62-71. 

Brouwer T, Todd DB et al (2002) Flow characteristics of screws and special mixing enhancers in a co-rotating twin screw extruder. Int Polym Process 17(l) 26-32 Carpenter J, Katayama D et al (2009) Measurement of Tg in lyophilized protein and protein exdpient mixtures by dynamic mechanical analysis. J Therm Anal Calorim 95 881-884 Chiang P-C, Ran Y et al (2012) Evaluation of drug load and polymer by using a 96-well plate vacuum dry system for amorphous solid dispersion drug delivery. AAPS Pharm Sci Tech 13(2) 713-722 Chokshi RJ, Sandhu HK et al (2005) Characterization of physico-mechanical properties of in-domethadn and polymers to assess their suitability for hot-melt extrusion process as a means to manufacture sohd dispersion/solution. J Pharm Sci 94(11) 2463-2474... 

Verreck G, Decorte A et al (2006a) The effect of pressurized carbon dioxide as a plasticizer and foaming agent on the hot melt extrusion process and extrudate properties of phaimaceutical polymers. J Supercrit Fluids 38(3) 383-391... 

Markl D, Wahl PR et al (2013) Supervisory control system for monitoring a pharmaceutical hot melt extrusion process. AAPS PharmSdTech 14 1034-1044 Montgomery DC, Keats JB et al (1994) Integrating statistical process control and engineering process control, J Qual Technol 26 79-87... 

Saerens L, Dierickx L et al (2011). Raman spectroscopy for the in-line polymer-drug quantification and solid state characterization during a pharmaceutical hot-melt extrusion process. Eur J Pharm Biopharm 77 158-163... 

Smith-Goettler B, Gendron CM, MacPhail N, Meyer RF, Phillips JX (2011) NIR monitoring of a hot-melt extrusion process. Spectrosc Lett... 

Miscibility can be predicted by locating the minimal viscosity point. This method can also provide the minimum hot-melt extrusion processing temperature. 

Polymers as Formulation Excipients for Hot-Melt Extrusion Processing of Pharmaceuticals... 

One of the numerous applications of polymers as formulation excipients in the pharmaceutical industry is their use as matrix formers in the hot-melt extrusion process. Although HME was invented at the end of the 18th century as a method of manufacturing metal parts, its potential for the production and treatment of polymers was recognized and has now become the main production method of plastic materials [1]. However, HME was only recently introduced in the pharmaceutical industry [2], but since its introduction it has opened a new area of industrial application for polymers in pharmaceutical formulation. 

Table 5.1 Polymers currently in use for the Hot-Melt Extrusion processing of pharmaceuticals, together with corresponding glass transition and melting temperatures [9,26].

To compare the simulated values with the hot-melt extrusion process, the feasible blends are produced through hot-melt extrusion, performed on a lab-scale ram extruder. Employing Eudragit RS as a thermal polymer that is known to form multiple unit-controlled release matrix particles [20,34-36], the purpose in respect of question 2 was to distinguish a system of low solubility for the drug compound. 

The physical states of the substances modeled differ at 298.15 K DSC measurements (see also Section 16.2.3.2) show that polymer Eudragit RS is amorphous without crystalline sections. In contrast, the plasticizers TEC, ATBC, and DBS are fluids. Furthermore, the drugs ibuprofen and theophylline are crystalline with ibuprofen melting within the hot-melt extrusion process, whereas theophylline stays solid. These differences were taken into account for the calculation of the solubility... 

In contrast, theophylline is melting at 270°C, so this drug remained crystalline during the entire hot-melt extrusion process and was only suspended in the polymer matrix. The compositions and glass transition temperatures of all samples produced by hot-melt extrusion are shown in Table 16.4. 

---