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Rational design of controlled release matrix tablets using an ethylcellulose dispersion and fluid bed granulation technology

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1991
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dissertation
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Application of an aqueous polymeric dispersion to control drug release from matrix tablets was investigated. The polymeric dispersion of ethylcellulose was applied as a binder in matrix tablet formulations prepared by fluid bed granulation. Examined were the effect of excipients (dicalcium phosphate, lactose, and microcrystalline cellulose), drug solubility (chlorpheniramine maleate and hydrochlorothiazide), level of water insoluble binder (5 to 30% w/w), and compression force (300 and 600 kg) on the granule and resulting tablet characteristics. These objectives were approached through the use of mixture experimental design. Examined also were the physico-chemical properties of the granules and tablets to further explain the in vitro release behavior of the different formulations. The mean particle size ranged from 85 to 700 {dollar}\mu{dollar}m and the majority of tablets possessed tensile strength values which ranged from 5 to 25 kg/cm{dollar}\sp2{dollar}. A critical assessment of the theoretical framework was tested by observing how the solubility of drug and excipient(s) changed the consolidation characteristics, porosity, and tortuosity of the matrix. Compression of the fluid bed granules into tablets was a requisite for sustained release of drug since the granules themselves rapidly released the drug. Excipients and level of binder had a major impact on the release characteristics of the tablets. In general, for tablets containing chlorpheniramine maleate higher binder levels and compression force decreased the release of drug from the matrix. In contrast, for tablets containing hydrochlorothiazide higher binder levels decreased the release of drug but the release was insensitive to compression force. Drug solubility played a disproportional role in the release rate with the more water soluble drug producing the fastest release in part due to the disruption of the matrix infrastructure. Addition of the polymeric dispersion to the raw materials, was found to decrease the mean yield value by 17 to 72% indicating increased plasticity of the granulations. The database generated from the mixture design was used to rationally fabricate matrix tablets which had a specified release rate least sensitive to compression force. This study demonstrates that a controlled release matrix system can be produced using an aqueous ethylcellulose dispersion and fluid bed granulation technology.

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University of Maryland, Baltimore. Pharmaceutical Sciences. Ph.D. 1991
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