PURPOSE• Amorphous formulations represent a promising

option to cope with the increasing number ofpoorly water-soluble drugs.1

• New polymeric carriers are necessary to formulatemore drugs in amorphous solid dispersions.2

• Glass transition, melting, and degradationtemperature determine polymer suitability for hotmelt extrusion.

• Combinations of interacting additivities andpolymers are a promising approach to develop newpolymeric matrices suitable for hot melt extrusionor even further manufacturing processes.

• Unlike polymers that are chemically modified, thedesigned carrier formulations in this work are notnew chemical entities so there is no burden oftoxicological qualification.

CONCLUSION(S)A molecularly modified matrix for hot melt extrusionwas successfully obtained as a polymeric glass byadding malic acid to Eudragit E without indication ofany phase separation. Furthermore, utilizingfenofibrate as a model compound highlighted thestabilizing and processing properties of the newlydesigned matrix. The idea to modify polymers non-chemically can be harnessed in the future to target aspecific increase or decrease of the glass transition,or for example, to tailor polymer swelling in water fora desired drug release. More research is needed withadditional compounds to explore this novel approachand to harness its full potential.

RESULT(S)

METHOD(S)• Prior to extrusion, the components were mixed in a

beaker. Hot melt extrudates were prepared on a co-rotating twin-screw extruder ZE9 ECO from Three-Tec at130°C and 80 rpm.

• As proof of the interaction a 13C NMR analysis wascarried out in deuterated DMSO.

• Dissolution studies were performed in a USP II apparatusat 100 filled with PBS pH 6.4 and 0.5 % SDS.

• Atomic force microscopy images for the detection ofphase separation were taken in the tapping mode of thecantilever. In this mode, the probe is oscillated near itsmechanical resonance frequency and tapping thesurface. If phase imaging mode is carried out, the phaseshift relative to the driving oscillator is monitored inaddition to the amplitude. Typically, the phase signal issensitive to variations in composition, adhesion, friction,viscoelasticity as well as other factors.

FUNDINGThis project has received funding from the European Union’s Horizon 2020 Research and InnovationProgram under grant agreement No 674909.

Proof of an interaction• The 13C NMR analysis showed a significant peak shift of the carboxylic carbon with the α-

hydroxyl group of malic acid in the formulation with Eudragit E and malic acid as well as afterthe addition of fenofibrate. Such a peak shift is in line with predictions performed with ACD-Labs (Figure 2).

• FTIR analysis revealed the disappearing of the hydroxyl peak of the same carboxyl group. 6

• This underlined the interaction between the carboxyl group of the malic acid and the Eudragit E

Effects of molecularly interacting additives on polymeric hot melt extrusionFelix Ditzinger1,2; Uta Scherer1; Monica Schönenberger3; Martin Kuentz1

1University of Applied Sciences and Arts of Northwestern Switzerland, Basel2University of Basel, Department of Pharmaceutical Sciences, Basel3University of Basel, Swiss Nanoscience Institute (SNI) - Nano Imaging, Basel

CONTACT INFORMATION: felix.ditzinger@fhnw.ch

Posternumber

Benefits of the designed polymeric matrix

• The dissolution showed the advanced properties of thenewly designed polymeric matrix. Faster dissolution andhigher overall release was observed.

• AFM images of two samples with malic acid and theformulation without additive showed phase separationshortly after the extrusion.

• This finding was in accordance with other microscopicanalysis.

REFERENCES1. Serajuddin, A. T. M. Solid Dispersion of Poorly Water‐soluble Drugs: Early Promises,Subsequent Problems, and Recent Breakthroughs. J. Pharm. Sci. 1999, 88 (10), 1058–1066.

2. Wyttenbach, N.; Kuentz, M. Glass‐Forming Ability of Compounds in Marketed AmorphousDrug Products. Eur. J. Pharm. Biopharm. 2017, 112, 204–208.

3. Kojima, T.; Higashi, K.; Suzuki, T.; Tomono, K.; Moribe, K.; Yamamoto, K. Stabilization of aSupersaturated Solution of Mefenamic Acid from a Solid Dispersion with EUDRAGIT® EPO.Pharm. Res. 2012, 29 (10), 2777–2791.

4. Saal, W.; Ross, A.; Wyttenbach, N.; Alsenz, J.; Kuentz, M. Unexpected Solubility Enhancementof Drug Bases in the Presence of a Dimethylaminoethyl Methacrylate Copolymer. Mol. Pharm.2018, 15 (1), 186–192.

5. Parikh, T.; Serajuddin, A. T. M. Development of Fast‐Dissolving Amorphous Solid Dispersionof Itraconazole by Melt Extrusion of Its Mixture with Weak Organic Carboxylic Acid andPolymer. Pharm. Res. 2018, 35 (7), 127.

6. Kasten, G.; Nouri, K.; Grohganz, H.; Rades, T.; Löbmann, K. Performance Comparisonbetween Crystalline and Co‐Amorphous Salts of Indomethacin‐Lysine. Int. J. Pharm. 2017, 533(1), 138–144.

MOLECULAR RATIONALE

Fenofibrate

Malic Acid

Eudragit E

Figure 3: Dissolution curves of the matrix extrusion (blacksquares), FE & EE extrudate (black dots) and physical mixtureFE & EE & MA (grey diamonds)

Figure 4: AFM phasing images of samples fromthe modified polymeric systems with FErepresented in the matrix extrusion (A), directextrusion (B) in comparison to the FE & EEextrudate (C)

• The dimethylamino group of Eudragit E can be utilized forinteractions with acidic compounds.3

• The Backbone of Eudragit E is available for interactionswith lipophilic drugs while the rather hydrophilic aminogroup could be masked.4

• Acidic additives have to be hydrophilic to avoid dissolutionissues of the formulation.

• Dicarboxylic acids provide a suitable melting point 5 andone group for the interaction with Eudragit E while theother carboxylic group is available to keep up suitabledissolution.

• Malic acid was selected out of initial trials with variousdicarboxylic acids.

Figure 2: 13C NMRspectra region between176 and 172 ppm of MA(green), MA and EE (red)and FE, MA, EE (blue)