Figure 2: Melt viscosity of pure polymers as a function of temperature

Investigation of the infl uence of plasticizers on the Tg of polymers showed in systems comprising PEG 1500 and Cremophor® RH 40 a pronounced tendency to decrease the Tg of polymers (Figures 3 + 4).

Figure 3: Tg of pure polymers in comparison to polymer-plasticizer combinations (extrudates, 9 : 1, w/w-%)

Figure 4: Tg of pure polymers in comparison to polymer-plasticizer combinations (extrudate and fi lm (*), 9 : 1, w/w-%), split bars represent presence of another Tg

Figure 5 shows the infl uence of plasticizers on the melt vis-cosity of Kollidon® VA 64. A considerable reduction in the viscosity was possible. The reduction of melt viscosity by plasticizer addition increases in the following: Cremophor® RH 40 < PEG 1500 < Lutrol® F 68.

Figure 5: Melt viscosity of Kollidon® VA 64 in comparison to Kollidon® VA 64 / plasticizer combinations (9 : 1, w/w-%)

The Chemical Company

Suitability of Plasticized Polymers for Hot Melt ExtrusionD. Djuric, M. Karl, K. Kolter, A. Maschke and S. Nalawade

R&D Project Management Excipients, BASF SE, 67056 Ludwigshafen, Germany

PBP World Meeting 2010 March 8–11, 2010, Valletta, Malta, G-EMP/MD284

IntroductionPolymers for hot melt extrusion must exhibit thermoplastic characteristics in order to permit the melt extrusion process and they must be stable at extrusion temperatures. Other relevant characteristics are: suitable glass transition tem-perature (Tg) of 50–180 °C, low hygroscopicity and no toxicity since larger amounts of polymer are used [1]. Extrudability of a polymer is mainly determined by the Tg and melt viscos-ity [2]. Polymers having a high molecular weight exhibit high melt viscosity and can hardly be extruded. Moreover, a high Tg requires a high processing temperature which can degrade sensitive actives [3]. As a general rule, an extrusion process should be run at temperatures 20–40 °C above the Tg. Most polymers demonstrate thixotropic behavior which means that the viscosity declines as a function of increasing shear stress. Therefore, this study was designed to investigate the infl uence of several plasticizers on the Tg and the melt viscosity of poly-mers.

Experimental MethodsMaterialsKollidon® VA 64, Kollidon® 12 PF, Kollidon® 17 PF, Kollidon® 30, Kollidon® 90 F and Kollidon® SR (BASF SE, Germany) were used as polymers. Lutrol® F 68, Cremophor® RH 40 and Plu-riol® E 1500 Powder K (PEG 1500) (BASF SE, Germany) were used as plasticizers.

ExtrusionMelt extrusion was performed using a twin screw extruder ZSK 25, Werner & Pfl eiderer (Germany) with a screw diam-eter of 25 mm and a length to diameter ratio of 34. Extrusion parameters were varied: Loading of the extruder from 4 to 5 kg/h, extrusion temperature: 60–150 °C and the rpm of the extruder screws from 100 to 150 rpm.

Film CastingA polymer and a plasticizer were dissolved in water. The so-lution was casted by Coatmaster, Erichsen Testing Equip-ment (Germany); knife with different die gaps (150–500 µm) and dried at 40 °C.

Differential Scanning Calorimetry (DSC)DSC studies were performed by using a Q2000 TA Instru-ments (USA). DSC scans were recorded at a heating rate of 20 K/min in the second heating run.

ViscosityViscosity studies were performed using a shear stress con-trolled rotational rheometer SR5 from Rheometrics (USA). The measurements were performed at three different temperatures with a plate to plate measuring geometry (diameter of 25 mm, height of 1 mm), angular frequency of 1.6 rad/s.

Results and DiscussionTaking the Tg and the melt viscosity into consideration, Kollidon® VA 64 and Kollidon® 12 PF revealed excellent suit-ability for extrusion. Povidones of higher molecular weight were diffi cult to extrude because of higher Tg and melt vis-cosities (Figures 1 + 2).

Figure 1: Tg and melting temperatures of pure polymers and plasticizers, respectively. Split bar represent presence of another Tg

PEG 1500 showed a strong infl uence on the Tg as well as on the melt viscosity of Kollidon® VA 64. The extrudates of Kolli-don® VA 64 in combination with Lutrol® F 68 and Cremophor® RH 40 were opaque in nature. While, the extrudate obtained using PEG 1500 were transparent. Based on the DSC results (Figures 6–8) and the visual inspection it may be concluded that PEG 1500 in contrast to the others form a single-phase mixture when melt extruded with Kollidon® VA 64.

Conclusion� The type of the plasticizer has a major infl uence on

the Tg and the melt viscosity of povidones and copo-vidone.

� Addition of PEG 1500 and Cremophor® RH 40 reduces the Tg of the polymer considerably.

� All plasticizers lower the melt viscosity when added to Kollidon® VA 64.

� It can be concluded that the presence of plasticizer signals in DSC runs of polymer-plasticizer extrudates correlates with the appearance of the extrudates. It indicates molecular miscibility or non-miscibility.

References[1] I. Ghebre-Sellassie, C. Martin, Pharmaceutical Extrusion

Technology, Drugs and the Pharmaceutical Sciences, Vol-ume 133 (2007)

[2] R. J. Chokshi, H. K. Sandhu, R. M. Iyer, N. H. Shaw, A. W. Malick and H. Zia, J. Pharm Sci. (94) 11, 2463–2474 (2005)

[3] S. Thumma, M. A. ElSohly, S. Q. Zhang, W. Gul, M. A. Rep-ka, European Journal of Pharmaceutics and Biopharma-ceutics (70) 2, 605–614 (Oct. 2005)

Figure 6– 8: DSC plots of Kollidon® VA 64, pure plasticizers and different Kollidon® VA 64 / plasticizer combinations (extrudates, 9 : 1, w/w-%)

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