In Vitro Evaluation of Enteric-Coated HPMC Capsules – Effect of Formulation Factors on Product Performance

A comparative study on different enteric-coated hard capsules was performed. The influence of different formulation factors like choice of enteric polymer, triethyl citrate (TEC) concentration (plasticizer), talc concentrations (anti-tacking agent), and different coating process parameters on the sealing performance of the capsule and the disintegration time were investigated. Furthermore, the influence of different disintegration test methods (with disc vs. without disc and 50 mM U.S. Pharmacopoeia (USP) buffer pH 6.8 vs. biopredictive 15 mM phosphate buffer pH 6.5) was evaluated. All formulations showed sufficient but not equivalent acid resistance when tested. Polymer type was the main factor influencing the capsule sealing and disintegration time. In addition, TEC and talc could affect the performance of the formulation. Regarding the choice of the disintegration test method, the presence of a disc had for the most part only limited influence on the results. The choice of disintegration buffer was found to be important in identifying differences between the formulations.

The performance of various enteric-coating formulations applied to HPMC capsules was investigated, and different performance parameters were evaluated. Regarding the gap sealing, HPMCP HP-55S showed the best performance (which seems to have been reflected in it achieving the best resistance to acid uptake). As for the disintegration times, they varied not only as a function of the polymer used but also as a function of coat formulation additives as well, with anti-tacking agents (talc) and plasticizers (TEC) exhibiting significant degrees of influence. Talc showed a positive effect on the gap closing. TEC can influence the surface smoothness of the coating, the sealing of the junction between the capsules body and cap, and the disintegration time and hence the drug release rate. The influence of TEC on disintegration time can go either in a positive or negative direction, because of the opposing effects of its water solubility on one hand and the enhanced film flexibility that imparts disintegration on the other. Moreover, emphasis should be put on the use of biopredictive methods to detect the influence of formulation factors (e.g., plasticizers) on product performance, where the non-biorelevant compendial medium missed such effects. All in all, film coating of two-piece HPMC capsules has been found to generally be a viable approach toward achieving enteric release properties despite the presence of a gap between the two capsule parts.

Download the full MDPI publication here: In Vitro Evaluation of Enteric-Coated HPMC Capsules – Effect of Formulation Factors on Product Performance

or continue reading here: Fu, M.; Blechar, J.A.; Sauer, A.; Al-Gousous, J.; Langguth, P. In Vitro Evaluation of Enteric-Coated HPMC Capsules—Effect of Formulation Factors on Product Performance. Pharmaceutics 2020, 12, 696.

Keywords: disintegration; biopredictive; enteric-coating; AQOAT; hypromellose acetate succinate (HPMCAS); hypromellose phthalate (HPMCP); Eudragit L100-55; formulation; capsules

Table 1. Polymers used in the present study

PolymerNameGradeFunction Related CharacteristicOpeningpH Value
Hypromellose acetate succinate, HPMCASShin-Etsu AQOAT®AS-LGAcetyl: 8.2%, Succinoyl: 14.9%>5.5
Hypromellose acetate succinate, HPMCASShin-Etsu AQOAT®AS-MGAcetyl: 9.3%, Succinoyl: 11.3%>6.0
Hypromellose acetate succinate, HPMCASShin-Etsu AQOAT®AS-HGAcetyl: 11.7%, Succinoyl: 7.5%>6.5
Hypromellose PhthalateHPMCPHP-50Phthalyl: 23.1%, Viscosity: 55 mPas>5.0
Hypromellose PhthalateHPMCPHP-55Phthalyl: 32.9%, Viscosity: 43 mPas>5.5
Hypromellose PhthalateHPMCPHP-55SPhthalyl: 33.2%, Viscosity: 167 mPas>5.5
Methacrylic acid and ethyl acrylate copolymerEudragit®L100-55Ratio of methacylic acid to ethyl acrylate ~1:1>5.5
Cellulose acetate phthalateEastmanTM C-A-PC-A-P Cellulose Ester NFAcetyl: 21.5–26%, Phthalyl: 30–36%>6.0
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