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Modulation of drug release kinetics from hydroxypropyl methyl cellulose matrix tablets using polyvinyl pyrrolidone.
Int J Pharm. 2007 Jun 07; 337(1-2):246-53.IJ

Abstract

Hydrophilic matrix tablets are widely used to extend the release of a broad range of pharmaceutically active materials. The mechanism and kinetics of drug release are dependent on the solubility of the active moiety and the swelling and erosion properties of the polymer, with water soluble compounds released predominantly by diffusion. The swelling and erosion properties of hydroxypropyl methyl cellulose (HPMC), typically lead to a first order release rate for water soluble compounds as opposed to the more desirable zero-order kinetics. In addition, for compounds with differences in regional absorption within the gastrointestinal tract a dosage form with a bi-modal release profile may be required, which is difficult to achieve with a simple dosage form. The following paper presents a simple, cost effective and elegant solution for achieving a range of predictable release profiles from linear to bi-modal for a water soluble drug (caffeine) from HPMC matrices, through the inclusion of polyvinyl pyrrolidone (PVP). Mechanistic studies using gel rheology, excipient dissolution and near-infrared microscopy (NIR) microscopy are presented which show that the modulation of drug release kinetics is mediated through a reduction in HPMC viscosity in the presence of a critical concentration of PVP, which leads to a break-up of the extended release tablet. A validated mathematical model is also presented which allows drug release profiles to be reliably predicted based on the initial HPMC and PVP content in the tablet.

Authors+Show Affiliations

Pharmaceutical Research & Development, Merck Sharp & Dohme Ltd., Hertford Road, Hoddesdon, Hertfordshire EN11 9BU, United Kingdom. ian_hardy@merck.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17306477

Citation

Hardy, Ian J., et al. "Modulation of Drug Release Kinetics From Hydroxypropyl Methyl Cellulose Matrix Tablets Using Polyvinyl Pyrrolidone." International Journal of Pharmaceutics, vol. 337, no. 1-2, 2007, pp. 246-53.
Hardy IJ, Windberg-Baarup A, Neri C, et al. Modulation of drug release kinetics from hydroxypropyl methyl cellulose matrix tablets using polyvinyl pyrrolidone. Int J Pharm. 2007;337(1-2):246-53.
Hardy, I. J., Windberg-Baarup, A., Neri, C., Byway, P. V., Booth, S. W., & Fitzpatrick, S. (2007). Modulation of drug release kinetics from hydroxypropyl methyl cellulose matrix tablets using polyvinyl pyrrolidone. International Journal of Pharmaceutics, 337(1-2), 246-53.
Hardy IJ, et al. Modulation of Drug Release Kinetics From Hydroxypropyl Methyl Cellulose Matrix Tablets Using Polyvinyl Pyrrolidone. Int J Pharm. 2007 Jun 7;337(1-2):246-53. PubMed PMID: 17306477.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of drug release kinetics from hydroxypropyl methyl cellulose matrix tablets using polyvinyl pyrrolidone. AU - Hardy,Ian J, AU - Windberg-Baarup,Anne, AU - Neri,Claudia, AU - Byway,Paul V, AU - Booth,Steven W, AU - Fitzpatrick,Shaun, Y1 - 2007/01/20/ PY - 2006/08/29/received PY - 2006/12/21/revised PY - 2007/01/10/accepted PY - 2007/2/20/pubmed PY - 2007/8/3/medline PY - 2007/2/20/entrez SP - 246 EP - 53 JF - International journal of pharmaceutics JO - Int J Pharm VL - 337 IS - 1-2 N2 - Hydrophilic matrix tablets are widely used to extend the release of a broad range of pharmaceutically active materials. The mechanism and kinetics of drug release are dependent on the solubility of the active moiety and the swelling and erosion properties of the polymer, with water soluble compounds released predominantly by diffusion. The swelling and erosion properties of hydroxypropyl methyl cellulose (HPMC), typically lead to a first order release rate for water soluble compounds as opposed to the more desirable zero-order kinetics. In addition, for compounds with differences in regional absorption within the gastrointestinal tract a dosage form with a bi-modal release profile may be required, which is difficult to achieve with a simple dosage form. The following paper presents a simple, cost effective and elegant solution for achieving a range of predictable release profiles from linear to bi-modal for a water soluble drug (caffeine) from HPMC matrices, through the inclusion of polyvinyl pyrrolidone (PVP). Mechanistic studies using gel rheology, excipient dissolution and near-infrared microscopy (NIR) microscopy are presented which show that the modulation of drug release kinetics is mediated through a reduction in HPMC viscosity in the presence of a critical concentration of PVP, which leads to a break-up of the extended release tablet. A validated mathematical model is also presented which allows drug release profiles to be reliably predicted based on the initial HPMC and PVP content in the tablet. SN - 0378-5173 UR - https://www.unboundmedicine.com/medline/citation/17306477/Modulation_of_drug_release_kinetics_from_hydroxypropyl_methyl_cellulose_matrix_tablets_using_polyvinyl_pyrrolidone_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(07)00040-3 DB - PRIME DP - Unbound Medicine ER -