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Extended release of flurbiprofen from tromethamine-buffered HPMC hydrophilic matrix tablets.
Pharm Dev Technol. 2018 Nov; 23(9):874-881.PD

Abstract

The pH-dependent solubility of a drug can lead to pH-dependent drug release from hydrophilic matrix tablets. Adding buffer salts to the formulation to attempt to mitigate this can impair matrix hydration and negatively impact drug release. An evaluation of the buffering of hydrophilic matrix tablets containing a pH-dependent solubility weak acid drug (flurbiprofen), identified as possessing a deleterious effect on hydroxypropyl methylcellulose (HPMC) solubility, swelling and gelation, with respect to drug dissolution and the characteristics of the hydrophilic matrix gel layer in the presence of tromethamine as a buffer was undertaken. The inclusion of tromethamine as an alkalizing agent afforded pH-independent flurbiprofen release from matrices based on both HPMC 2910 (E series) and 2208 (K series), while concomitantly decreasing the apparent critical effect on dissolution mediated by this drug with respect to the early pseudo-gel layer formation and functionality. Drug release profiles were unaffected by matrix pH-changes resulting from loss of tromethamine over time, suggesting that HPMC inhibited precipitation of drug from supersaturated solution in the hydrated matrix. We propose that facilitation of diffusion-based release of potentially deleterious drugs in hydrophilic matrices may be achieved through judicious selection of a buffering species.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Pygall S
a Department of Pharmacy , University of Nottingham , Nottingham , UK. b Commercial Trade Channels , Merck Sharp and Dohme Ltd , Hoddesdon , UK.
Kujawinski S
a Department of Pharmacy , University of Nottingham , Nottingham , UK. c SarKon Ltd , Llanelli , UK.
Timmins P
d Drug Product Science and Technology , Bristol-Myers Squibb Pharmaceuticals Ltd , Moreton , UK. e Department of Pharmacy , University of Huddersfield , Huddersfield, UK.
Melia C
a Department of Pharmacy , University of Nottingham , Nottingham , UK.

MeSH

Delayed-Action PreparationsDrug CompoundingDrug LiberationFlurbiprofenHypromellose DerivativesTabletsTromethamine

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28298171

Citation

Pygall, Samuel, et al. "Extended Release of Flurbiprofen From Tromethamine-buffered HPMC Hydrophilic Matrix Tablets." Pharmaceutical Development and Technology, vol. 23, no. 9, 2018, pp. 874-881.
Pygall S, Kujawinski S, Timmins P, et al. Extended release of flurbiprofen from tromethamine-buffered HPMC hydrophilic matrix tablets. Pharm Dev Technol. 2018;23(9):874-881.
Pygall, S., Kujawinski, S., Timmins, P., & Melia, C. (2018). Extended release of flurbiprofen from tromethamine-buffered HPMC hydrophilic matrix tablets. Pharmaceutical Development and Technology, 23(9), 874-881. https://doi.org/10.1080/10837450.2017.1301470
Pygall S, et al. Extended Release of Flurbiprofen From Tromethamine-buffered HPMC Hydrophilic Matrix Tablets. Pharm Dev Technol. 2018;23(9):874-881. PubMed PMID: 28298171.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Extended release of flurbiprofen from tromethamine-buffered HPMC hydrophilic matrix tablets. AU - Pygall,Samuel, AU - Kujawinski,Sarah, AU - Timmins,Peter, AU - Melia,Colin, Y1 - 2017/03/16/ PY - 2017/3/17/pubmed PY - 2018/12/12/medline PY - 2017/3/17/entrez KW - Drug–polymer interaction KW - HPMC KW - flurbiprofen KW - pH-independent dissolution KW - tromethamine SP - 874 EP - 881 JF - Pharmaceutical development and technology JO - Pharm Dev Technol VL - 23 IS - 9 N2 - The pH-dependent solubility of a drug can lead to pH-dependent drug release from hydrophilic matrix tablets. Adding buffer salts to the formulation to attempt to mitigate this can impair matrix hydration and negatively impact drug release. An evaluation of the buffering of hydrophilic matrix tablets containing a pH-dependent solubility weak acid drug (flurbiprofen), identified as possessing a deleterious effect on hydroxypropyl methylcellulose (HPMC) solubility, swelling and gelation, with respect to drug dissolution and the characteristics of the hydrophilic matrix gel layer in the presence of tromethamine as a buffer was undertaken. The inclusion of tromethamine as an alkalizing agent afforded pH-independent flurbiprofen release from matrices based on both HPMC 2910 (E series) and 2208 (K series), while concomitantly decreasing the apparent critical effect on dissolution mediated by this drug with respect to the early pseudo-gel layer formation and functionality. Drug release profiles were unaffected by matrix pH-changes resulting from loss of tromethamine over time, suggesting that HPMC inhibited precipitation of drug from supersaturated solution in the hydrated matrix. We propose that facilitation of diffusion-based release of potentially deleterious drugs in hydrophilic matrices may be achieved through judicious selection of a buffering species. SN - 1097-9867 UR - https://www.unboundmedicine.com/medline/citation/28298171/Extended_release_of_flurbiprofen_from_tromethamine_buffered_HPMC_hydrophilic_matrix_tablets_ DB - PRIME DP - Unbound Medicine ER -