Results and conclusion
Figure 1: Dissolution in citrate of 0.5 and 2.0% calcium-alginate gels containing aurintricarboxylic acid (1 mg/mL). (FIGURES
ARE COURTESY OF T.J. SMITH)
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Within the range of calcium and alginate tested, alginate was confirmed as the most important formulation variable in this
system and was associated with the greatest change in dissolution time (see Figures 1 and 2). Variation in calcium yielded
little change in the dissolution time (see Figure 2).
Figure 2: Effect of calcium chloride on the citrate-mediated dissolution of 0.5 and 2.0% alginate gels. The citrate concentration
was 132 mM.
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Although a single concentration of ATA was used, variations in the concentration of this polyanion must be considered if ATA
and its derivatives are to be advanced for preclinical or clinical evaluation. Nevertheless, these results reflect the importance
of alginate-concentration changes, regardless of the anti-HIV agent under consideration. The results also verified the importance
of citrate concentration because dissolution time appeared to be inversely proportional to citrate concentration (see Figure
1). Citrate in seminal fluid at a concentration of ~132 mM) is reduced by as much as 50% in certain disease processes (7).
While this reduction in citrate would be expected to decrease the release rate of drug from the formulation, total dissolution
occurred at both citrate concentrations. Microgranular cellulose yielded suppositories of a prototype that may yield sustained-release
characteristics in the presence of citrate. The properties of the suppositories and the dissolution time are summarized in
Table I.
Table I: Characteristics of manually fabricated prototype suppositories.
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In addition to its utility to viscosity enhancement for manual fabrication of the prototype suppositories, cellulose is relatively
inexpensive and safe to use for intravaginal and intrarectal applications (4, 5). This formulation's capability to alter release
rates for anti-HIV drugs, as well as the simplicity of design, deserves further consideration and investigation.
Timothy J. Smith* is a professor and chair of the Department of Physiology and Pharmacology, and Lara Haddad, Soraia Faizyar, Evelyn Valdez, Elizabeth Gramer, Layla S. Derreja, and Stefany M. Bowers are doctoral students, all at Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA 95211, tel. 209.946.3168,
fax 209.946.2857, tsmith@pacific.edu
.
*To whom all correspondence should be addressed.
Submitted: Aug. 25, 2009. Accepted: Oct. 7, 2009.
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3. J. LaBonte, J. Lebbos, and P. Kirkpatrick, Nat. Rev. Drug Discov.
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4. A.R. Neurath, N. Engl. J. Med.
359 (19), 2066–2067 (2008).
5. V.M.K. Ndesendo et al., AAPS PharmSciTech.
9 (2), 505–520 (2008).
6. T.J. Smith, Curr. Top. Biotechnol.
1, 129–132 (2004).
7. E.E. Kline et al., J. Urol.
176 (5), 2274–2279 (2006).
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