Pharmaceutical Technology: Controlled Drug Release, Volume 2

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CH. 16] TOBRAMYCIN SULPHATE FROM POLYMETHYLMETHACRYLATE IMPLANTS 177 Table 2—Effect of formulation factors on computer-generated fast (α) and slow (β) phase rate constants a No additives. drug to polymer (dry weight. Studies by Wilson et al. also showed that substantial amounts of tobramycin remain in the beads after 28 days. Our studies indicated that the inclusion of water-soluble additives could alter both the rate and extent of tobramycin release from Palacos PMMA. The three additives PEG 3400, PEG 400 and lactose significantly affected the slower diffusion phase of the matrix (Fig. 2 and Table 2). Law et al. [15] determined the diffusion coefficient for benzyl penicillin in thin films of Palacos, Simplex and CMW cements assuming that antibiotic transport can be described by Fick’s law using a finite difference approximation to quantify transient non-steady-state behaviour. These investigators found that the diffusion coefficient was increased in the presence of additives and proposed that the finite difference approach could be applied to determine release of antibiotic from preloaded PMMA beads. Dittgen and Stahlkopf [16] showed that incorporation of amino acids of varying solubilities also affected release of chloramphenicol from polymethacrylic
178 IMPLANTS [CH. 16 Fig. 1—The effect of drug loading on tobramycin sulphate release profiles. The solid lines represent the lines of best fit. The symbols represent the observed values. Fig. 2—The effect of incorporation of 10% water-soluble additives on tobramycin sulphate release profiles. The solid lines represent the lines of best fit. The symbols represent the observed values. implants. Our studies indicated that, while the presence of lactose and PEG 3400 increased the extent of release to about 50%, PEG 400 had a much more pronounced effect, increasing the extent of release to about 85% after three weeks. Fig. 3 illustrates the effect of increasing PEG concentrations on rate and extent of tobramycin release. Incorporation of 30% PEG resulted in almost complete release (>95%) within 3 days. Table 2 indicates that the initial rapid rate of release did not differ significantly while differences were observed with the slower diffusion phase. The changes in the rates and extents of
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PHARMACEUTICAL TECHNOLOGY Controlle
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3 TABLET MACHINE INSTRUMENTATION IN
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First published in 1991 by ELLIS HO
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7 10 Controlled delivery of theophy
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Slow and steady wins the race Poems
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1 Influence of drug solubility in t
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CH. 1] INFLUENCE OF DRUG SOLUBILITY
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24 MATRIX FORMULATIONS [CH. 2 MATER
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26 MATRIX FORMULATIONS [CH. 2 Fig.
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28 MATRIX FORMULATIONS [CH. 2 Table
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30 MATRIX FORMULATIONS [CH. 2 The e
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34 CH. 3] THE FORMULATION OF SUSTAI
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4 Statistical optimization of a con
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MATRIX FORMULATIONS [CH. 4 45 (4) G
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MATRIX FORMULATIONS [CH. 4 47 Fig.
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Columns 1-4 lead to the matrix of e
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MATRIX FORMULATIONS [CH. 4 51 Table
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MATRIX FORMULATIONS [CH. 4 53 Fig.
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Fig. 5—Linearization of the relea
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58 MATRIX FORMULATIONS [CH. 5 Pevik
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60 MATRIX FORMULATIONS [CH. 5 The d
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6 Controlled release matrix tablets
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CH. 6] CONTROLLED RELEASE MATRIX TA
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7 A new ibuprofen pulsed release or
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CH. 7] A NEW IBUPROFEN PULSED RELEA
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90 CH. 8] TOPICAL RELEASE AND PERME
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104 MULTIPARTICULATES [CH. 9 parace
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108 MULTIPARTICULATES [CH. 9 Fig. 2
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118 CH. 10] CONTROLLED DELIVERY OF
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Pharmaceutical Technology: Controlled Drug Release, Volume 2

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