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Application of a binary polymer system in drug release rate modulation. 1. Characterization of release mechanism.
J Pharm Sci. 1997 Mar; 86(3):316-22.JP

Abstract

A new binary polymer matrix tablet for oral administration was developed. The system will deliver drug at variable rates according to zero-order kinetics for total drug content and is manufactured by direct compression technology. Highly methoxylated pectin and hydroxypropyl methylcellulose (HPMC) at different ratios were used as major formulation components, and prednisolone was used as the drug model. The results indicate that by increasing pectin:HPMC ratios, release rates are increased, but zero-order kinetics prevail throughout the dissolution period (e.g., 3-22 h). Different pectin:HPMC ratios provide a range of viscosities that modulates drug release and results in rapid hydration/gelation in both axial and radial directions, as evidenced by photomicrographic pictures. This hydration-gelation contributes to the development of swelling/erosion boundaries and consequently to constant drug release. Combination of these particular polymers facilitates rapid formation of necessary boundaries (i.e., gel layer and solid core boundaries) to control overall mass transfer processes. The drug fraction released (Mt/M infinity), release kinetics, and mechanism of release were analyzed by applying the simple power law expression Mt/M infinity = kt(n), where k is a kinetic constant and the exponent n is indicative of the release mechanism. The calculated n values for pectin:HPMC ratios of 4:5, 3:6, and 2:7 were >0.95, which is indicative of a Case II transport mechanism (polymer relaxation/dissolution). The achievement of total zero-order kinetics is due to the predictable swelling/erosion and final polymer chain deaggregation and dissolution that is regulated by the gelling characteristics of polymers in the formulation.

Authors+Show Affiliations

Temple University, School of Pharmacy, Philadelphia, PA 19140, USA.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9050799

Citation

Kim, H, and R Fassihi. "Application of a Binary Polymer System in Drug Release Rate Modulation. 1. Characterization of Release Mechanism." Journal of Pharmaceutical Sciences, vol. 86, no. 3, 1997, pp. 316-22.
Kim H, Fassihi R. Application of a binary polymer system in drug release rate modulation. 1. Characterization of release mechanism. J Pharm Sci. 1997;86(3):316-22.
Kim, H., & Fassihi, R. (1997). Application of a binary polymer system in drug release rate modulation. 1. Characterization of release mechanism. Journal of Pharmaceutical Sciences, 86(3), 316-22.
Kim H, Fassihi R. Application of a Binary Polymer System in Drug Release Rate Modulation. 1. Characterization of Release Mechanism. J Pharm Sci. 1997;86(3):316-22. PubMed PMID: 9050799.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Application of a binary polymer system in drug release rate modulation. 1. Characterization of release mechanism. AU - Kim,H, AU - Fassihi,R, PY - 1997/3/1/pubmed PY - 2000/7/19/medline PY - 1997/3/1/entrez SP - 316 EP - 22 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 86 IS - 3 N2 - A new binary polymer matrix tablet for oral administration was developed. The system will deliver drug at variable rates according to zero-order kinetics for total drug content and is manufactured by direct compression technology. Highly methoxylated pectin and hydroxypropyl methylcellulose (HPMC) at different ratios were used as major formulation components, and prednisolone was used as the drug model. The results indicate that by increasing pectin:HPMC ratios, release rates are increased, but zero-order kinetics prevail throughout the dissolution period (e.g., 3-22 h). Different pectin:HPMC ratios provide a range of viscosities that modulates drug release and results in rapid hydration/gelation in both axial and radial directions, as evidenced by photomicrographic pictures. This hydration-gelation contributes to the development of swelling/erosion boundaries and consequently to constant drug release. Combination of these particular polymers facilitates rapid formation of necessary boundaries (i.e., gel layer and solid core boundaries) to control overall mass transfer processes. The drug fraction released (Mt/M infinity), release kinetics, and mechanism of release were analyzed by applying the simple power law expression Mt/M infinity = kt(n), where k is a kinetic constant and the exponent n is indicative of the release mechanism. The calculated n values for pectin:HPMC ratios of 4:5, 3:6, and 2:7 were >0.95, which is indicative of a Case II transport mechanism (polymer relaxation/dissolution). The achievement of total zero-order kinetics is due to the predictable swelling/erosion and final polymer chain deaggregation and dissolution that is regulated by the gelling characteristics of polymers in the formulation. SN - 0022-3549 UR - https://www.unboundmedicine.com/medline/citation/9050799/Application_of_a_binary_polymer_system_in_drug_release_rate_modulation__1__Characterization_of_release_mechanism_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(15)50259-1 DB - PRIME DP - Unbound Medicine ER -