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Hydrophilic matrices for controlled drug delivery: an improved mathematical model to predict the resulting drug release kinetics (the "sequential layer" model).
Pharm Res. 2000 Oct; 17(10):1290-8.PR

Abstract

PURPOSE

The aims of this study were (i) to elucidate the transport mechanisms involved in drug release from hydrophilic matrices; and (ii) to develop an improved mathematical model allowing quantitative predictions of the resulting release kinetics.

METHODS

Our previously presented model has been substantially modified, by adding: (i) inhomogeneous swelling; (ii) poorly water-soluble drugs; and (iii) high initial drug loadings. The validity of the improved model has been tested experimentally using hydroxypropyl methylcellulose (HPMC)-matrices, containing either a poorly or a freely water-soluble drug (theophylline or chlorpheniramine maleate) at various initial loadings in phosphate buffer pH 7.4 and 0.1 N HCl, respectively.

RESULTS

By overcoming the assumption of homogeneous swelling we show that the agreement between theory and experiment could be significantly improved. Among others, the model could describe quantitatively even the very complex effect on the resulting relative release rates (first slowing down, then accelerating drug release) observed when increasing the initial loading of poorly water-soluble drugs.

CONCLUSIONS

The practical benefit of this work is an improved design model that can be used to predict accurately the required composition and dimensions of drug-loaded hydrophilic matrices in order to achieve desired release profiles, thus facilitating the development of new pharmaceutical products.

Authors+Show Affiliations

Siepmann J
College of Pharmacy, Freie Universität Berlin, Germany. siepmann@med.univ-angers.fr
Peppas NA
No affiliation info available

MeSH

Chemistry, PharmaceuticalChlorpheniramineDelayed-Action PreparationsDiffusionHypromellose DerivativesKineticsMethylcelluloseModels, ChemicalReproducibility of ResultsSolubilityTheophyllineWater

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11145237

Citation

Siepmann, J, and N A. Peppas. "Hydrophilic Matrices for Controlled Drug Delivery: an Improved Mathematical Model to Predict the Resulting Drug Release Kinetics (the "sequential Layer" Model)." Pharmaceutical Research, vol. 17, no. 10, 2000, pp. 1290-8.
Siepmann J, Peppas NA. Hydrophilic matrices for controlled drug delivery: an improved mathematical model to predict the resulting drug release kinetics (the "sequential layer" model). Pharm Res. 2000;17(10):1290-8.
Siepmann, J., & Peppas, N. A. (2000). Hydrophilic matrices for controlled drug delivery: an improved mathematical model to predict the resulting drug release kinetics (the "sequential layer" model). Pharmaceutical Research, 17(10), 1290-8.
Siepmann J, Peppas NA. Hydrophilic Matrices for Controlled Drug Delivery: an Improved Mathematical Model to Predict the Resulting Drug Release Kinetics (the "sequential Layer" Model). Pharm Res. 2000;17(10):1290-8. PubMed PMID: 11145237.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydrophilic matrices for controlled drug delivery: an improved mathematical model to predict the resulting drug release kinetics (the "sequential layer" model). AU - Siepmann,J, AU - Peppas,N A, PY - 2001/1/6/pubmed PY - 2001/3/7/medline PY - 2001/1/6/entrez SP - 1290 EP - 8 JF - Pharmaceutical research JO - Pharm Res VL - 17 IS - 10 N2 - PURPOSE: The aims of this study were (i) to elucidate the transport mechanisms involved in drug release from hydrophilic matrices; and (ii) to develop an improved mathematical model allowing quantitative predictions of the resulting release kinetics. METHODS: Our previously presented model has been substantially modified, by adding: (i) inhomogeneous swelling; (ii) poorly water-soluble drugs; and (iii) high initial drug loadings. The validity of the improved model has been tested experimentally using hydroxypropyl methylcellulose (HPMC)-matrices, containing either a poorly or a freely water-soluble drug (theophylline or chlorpheniramine maleate) at various initial loadings in phosphate buffer pH 7.4 and 0.1 N HCl, respectively. RESULTS: By overcoming the assumption of homogeneous swelling we show that the agreement between theory and experiment could be significantly improved. Among others, the model could describe quantitatively even the very complex effect on the resulting relative release rates (first slowing down, then accelerating drug release) observed when increasing the initial loading of poorly water-soluble drugs. CONCLUSIONS: The practical benefit of this work is an improved design model that can be used to predict accurately the required composition and dimensions of drug-loaded hydrophilic matrices in order to achieve desired release profiles, thus facilitating the development of new pharmaceutical products. SN - 0724-8741 UR - https://www.unboundmedicine.com/medline/citation/11145237/Hydrophilic_matrices_for_controlled_drug_delivery:_an_improved_mathematical_model_to_predict_the_resulting_drug_release_kinetics__the_"sequential_layer"_model__ DB - PRIME DP - Unbound Medicine ER -