Pharmaceutical Excipients for Hot-Melt Extrusion - Pharmaceutical Technology

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Pharmaceutical Excipients for Hot-Melt Extrusion
The authors examine the influence of glass-transition temperature, melt viscosity, degredation temperature, and process settings.


Pharmaceutical Technology
Volume 35, Issue 5, pp. 74-82

Physicochemical characteristics of polymer–plasticizer combinations


Figure 4: Glass-transition temperature (Tg) of pure polymers in comparison with polymer–plasticizer combinations (extrudate, 9:1, w/w%).
T g can be reduced by adding plasticizers. An investigation on polymers used in combination with poloxamer 188, MGHS 40, and PEG 1500 was performed to observe the influence of these plasticizers on T g , temperature range of polymers for extrusion, and melt viscosity (see Figures 4 and 5).


Figure 5: Glass-transition temperature (Tg) of pure polymers in comparison with polymer–plasticizer combinations [extrudate and film (*), 9:1, w/w%], another color in the bar represents the presence of second Tg.
The additives tested acted in different ways. PEG 1500 and MGHS 40 decreased T g in all systems significantly, but poloxamer 188 had no effect on several polymers. From these results, it can be concluded that PEG 1500 and MGHS 40 dissolve more homogeneously in most of the polymers tested than poloxamer 188 does. This result can be related to the higher molecular weight of the poloxamer.

Processability


Figure 6: Temperature range of polymers and PEG 1500 combinations for extrusion (9:1, w/w%).
Taking the T g or T m , the melt viscosity, the T deg , and the determination of the lowest and highest processing temperatures by HME into consideration, the pure polymers copovidone, PEG-VCap-VAc, povidone 12, and poloxamer 407 demonstrated excellent suitability for extrusion (see Figure 6). Povidone 17, PVAc+PVP, PEG–VA, and PEG–VA + PVA were difficult to extrude because of their high T g or T m , melt viscosities, and the small difference between T deg and T g . PVPs of higher molecular weight (povidone 30 and povidone 90) and MA-EA as pure polymers were not processed by HME because of their degradation.

Three plasticizers (poloxamer 188, MGHS 40, and PEG 1500) were investigated in combination with these polymers. In general, 10 % (w/w) of the plasticizers was sufficient to decrease extrusion temperatures significantly (see Figure 6). Poloxamer 188 and PEG 1500 could be added in powder form using a separate powder feeder. MGHS 40 was added in molten form using a melt pump. The temperature range for extrusion was determined according to the method employed for the pure polymers.

All the polymer–plasticizer combinations could be processed below the processing temperatures of the pure polymers. However, this reduction in temperature was not the same for all polymers. The highest reduction of 50 C was observed for PVAc+PVP with all three plasticizers. This result is consistent with previous studies on the plasticizing effects in film coatings based on polyvinyl acetate, where small amounts also showed a tremendous effect.

The type of plasticizer also had a significant effect; PEG 1500 decreased the extrusion temperatures more than the other plasticizers. This result probably can be attributed to the low molecular weight of this plasticizer.

Conclusion

Suitable T g (T m ), T deg , and melt viscosity are relevant physicochemical parameters of the polymer in HME. A large range between T g (T m ) and T deg of the polymer is highly beneficial because it offers freedom for developing the extrusion process. PEG–VCap–VAc is characterized by the widest temperature range for extrusion, followed by povidone 12, and copovidone.

The type of plasticizer has a major influence on T g , melt viscosity, and the temperature range of the polymer in the HME process. A plasticizer principally enables extrusion processes to occur at low temperatures.

The knowledge of polymer and plasticizer characteristics and their effects on the extrusion process and resulting extrudates is an important prerequisite for the quick and successful development of an extruded drug-delivery system.

Matthias Karl* and Dejan Djuric, PhD, are managers of research and development for pharmaceutical ingredients, and Karl Kolter, PhD, is head of research and development for pharmaceutical ingredients, all at BASF, G-ENP/MD - H 201, 67056 Ludwigshafen, Germany, tel. +49 621 60 92337, fax +49 621 60 97370,
.

*To whom all correspondence should be addressed.

Submitted: Feb. 17, 2011. Accepted: Apr. 1, 2011.


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