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pH-independent immediate release polymethacrylate formulations : an observational study

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Abstract
Using Eudragit (R) E PO (EudrE) as a polymethacrylate carrier, the aim of the study was to develop a pH-independent dosage form containing ibuprofen (IBP) as an active compound via chemical modification of the polymer (i.e. quaternization of amine function) or via the addition of dicarboxylic acids (succinic, glutaric and adipic acid) to create a pH micro-environment during dissolution. Biconvex tablets (diameter: 10mm; height: 5mm) were produced via hot melt extrusion and injection molding. In vitro dissolution experiments revealed that a minimum of 25% of quaternization was sufficient to partially (up to pH 5) eliminate the pH-dependent effect of the EudrE/IBP formulation. The addition of dicarboxylic acids did not alter IBP release in a pH 1 and 3 medium as the dimethyl amino groups of EudrE are already fully protonated, while in a pH 5 solvent IBP release was significantly improved (cf. from 0% to 92% release after 1h dissolution experiments upon the addition of 20wt.% succinic acid). Hence, both approaches resulted in a pH-independent (up to pH 5) immediate release formulation. However, the presence of a positively charged polymer induced stability issues (recrystallization of API) and the formulations containing dicarboxylic acids were classified as mechanically unstable. Hence, further research is needed to obtain a pH-independent immediate release formulation while using EudrE as a polmethacrylate carrier.
Keywords
extrusion, immediate release, drug delivery, injection molding, polymers, HOT-MELT EXTRUSION, BACTERIAL OVERGROWTH, SOLID DISPERSIONS, PHARMACEUTICAL APPLICATIONS, DRUG-RELEASE, PART II, IBUPROFEN, POLYMERS, TABLETS, FILMS

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Chicago
Claeys, Bart, Reinout Vandeputte, Bruno De Geest, Jean Paul Remon, and Chris Vervaet. 2016. “pH-independent Immediate Release Polymethacrylate Formulations : an Observational Study.” Drug Development and Industrial Pharmacy 42 (4): 578–583.
APA
Claeys, Bart, Vandeputte, R., De Geest, B., Remon, J. P., & Vervaet, C. (2016). pH-independent immediate release polymethacrylate formulations : an observational study. DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, 42(4), 578–583.
Vancouver
1.
Claeys B, Vandeputte R, De Geest B, Remon JP, Vervaet C. pH-independent immediate release polymethacrylate formulations : an observational study. DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY. 2016;42(4):578–83.
MLA
Claeys, Bart, Reinout Vandeputte, Bruno De Geest, et al. “pH-independent Immediate Release Polymethacrylate Formulations : an Observational Study.” DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY 42.4 (2016): 578–583. Print.
@article{8040310,
  abstract     = {Using Eudragit (R) E PO (EudrE) as a polymethacrylate carrier, the aim of the study was to develop a pH-independent dosage form containing ibuprofen (IBP) as an active compound via chemical modification of the polymer (i.e. quaternization of amine function) or via the addition of dicarboxylic acids (succinic, glutaric and adipic acid) to create a pH micro-environment during dissolution. Biconvex tablets (diameter: 10mm; height: 5mm) were produced via hot melt extrusion and injection molding. In vitro dissolution experiments revealed that a minimum of 25\% of quaternization was sufficient to partially (up to pH 5) eliminate the pH-dependent effect of the EudrE/IBP formulation. The addition of dicarboxylic acids did not alter IBP release in a pH 1 and 3 medium as the dimethyl amino groups of EudrE are already fully protonated, while in a pH 5 solvent IBP release was significantly improved (cf. from 0\% to 92\% release after 1h dissolution experiments upon the addition of 20wt.\% succinic acid). Hence, both approaches resulted in a pH-independent (up to pH 5) immediate release formulation. However, the presence of a positively charged polymer induced stability issues (recrystallization of API) and the formulations containing dicarboxylic acids were classified as mechanically unstable. Hence, further research is needed to obtain a pH-independent immediate release formulation while using EudrE as a polmethacrylate carrier.},
  author       = {Claeys, Bart and Vandeputte, Reinout and De Geest, Bruno and Remon, Jean Paul and Vervaet, Chris},
  issn         = {0363-9045},
  journal      = {DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY},
  language     = {eng},
  number       = {4},
  pages        = {578--583},
  title        = {pH-independent immediate release polymethacrylate formulations : an observational study},
  url          = {http://dx.doi.org/10.3109/03639045.2015.1057151},
  volume       = {42},
  year         = {2016},
}

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