Search tips
Search criteria 


Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
AAPS PharmSciTech. 2007 October; 8(4): 305–311.
Published online 2007 December 28. doi:  10.1208/pt0804118
PMCID: PMC2750704

Studies on a novel doughnut-shaped minitablet for intraocular drug delivery


The objective of this study was to evaluate the effect of 2 independent formulation variables on the drug release from a novel doughnut-shaped minitablet (DSMT) in order to optimize formulations for intraocular drug delivery. Formulations were based on a 32 full-factorial design. The 2 independent variables were the concentration of Resomer (% wt/wt) and the type of Resomer grade (RG502, RG503, and RG504), respectively. The evaluated response was the drug release rate constant computed from a referenced marketed product and in vitro drug release data obtained at pH 7.4 in simulated vitreous humor. DSMT devices were prepared containing either of 2 model drugs, ganciclovir or foscarnet, using a Manesty F3 tableting press fitted with a novel central-rod, punch, and die setup. Dissolution data revealed biphasic drug release behavior with 55% to 60% drug released over 120 days. The inherent viscosity of the various Resomer grades and the concentration were significant to achieve optimum release rate constants. Using the resultant statistical relationships with the release rate constant as a response, the optimum formulation predicted for devices formulated with foscarnet was 70% wt/wt of Resomer RG504, while 92% wt/wt of Resomer RG503 was ideal for devices formulated with ganciclovir. The results of this study revealed that the full-factorial design was a suitable tool to predict an optimized formulation for prolonged intraocular drug delivery.

Full Text

The Full Text of this article is available as a PDF (238K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Gotti R, Furlanetto S, Andrisano V, Cavirini V, Pinzauti S. Design of experiments for capillary electrophoretic enantioresolution of salbutamol using dermatan sulphate. J Chromatog A. 2000;875:411–422. doi: 10.1016/S0021-9673(99)01303-5. [PubMed] [Cross Ref]
2. McCarron PA, Woolfson AD, Keating SM. Response surface methodology as a predictive tool for determining the effects of preparation conditions on the physicochemical properties of poly (isobutylcyanoacrylate) nanoparticles. Int J Pharm. 1999;193:37–47. doi: 10.1016/S0378-5173(99)00311-7. [PubMed] [Cross Ref]
3. Pillay V, Danckwerts MP. Textural profiling and statistical optimization of cross-linked calcium-alginate-pectinate-cellulose acetophthalate gelisphere matrices. J Pharm Sci. 2002;91:2559–2570. doi: 10.1002/jps.10251. [PubMed] [Cross Ref]
4. Kimura H, Ogura Y, Hashizoe M, Nishiwaki H, Honda Y, Ikada Y. A new vitreal drug delivery system using an implantable biodegradable polymeric device. Invest Ophthalmol Vis Sci. 1994;35:2815–2819. [PubMed]
5. Martinez-Sancho C, Herrero-Vanrell R, Negro S. Optimization of acyclovir poly(d,1-lactide-co-glycolide) microspheres for intravitreal administration using a factorial design study. Int J Pharm. 2004;273:45–56. doi: 10.1016/j.ijpharm.2003.12.006. [PubMed] [Cross Ref]
6. Vandervoort J, Ludwig A. Biocompatible stabilizers in the preparation of PLGA nanoparticles: a factorial design study. Int J Pharm. 2002;238:77–92. doi: 10.1016/S0378-5173(02)00058-3. [PubMed] [Cross Ref]
7. Yasukawa T, Kimura H, Kunou N, et al. Biodegradable scleral implant for intravitreal controlled release of ganciclovir. Graefes Arch Clin Exp Ophthalmol. 2000;238:186–190. doi: 10.1007/s004170050031. [PubMed] [Cross Ref]
8. Sanborn GE, Anand R, Torti RE, et al. Sustained-release ganciclovir therapy for treatment of cytomegalovirus retinitis. Arch Ophthalmol. 1992;110:188–195. [PubMed]
9. Martinez-Sancho C, Herrero-Vanrell R, Negro S. Poly (D,L-lactide-co-glycolide) microspheres for long-term intravitreal delivery for acyclovir: influence of fatty and non-fatty additives. J Microencapsul. 2003;20:799–810. doi: 10.1080/02652040310001600532. [PubMed] [Cross Ref]
10. Martin DF, Parks DJ, Mellow SD, et al. Treatment of cytomegalovirus retinitis with an intraocular sustained-release ganciclovir implant: a randomized controlled clinical trial. Arch Ophthalmol. 1994;112:1531–1539. [PubMed]
11. Fonner DE, Buck JR, Banker GS. Mathematical optimization techniques in drug product design and process analysis. J Pharm Sci. 1970;59:1587–1596. doi: 10.1002/jps.2600591110. [PubMed] [Cross Ref]
12. Moritera T, Ogura Y, Honda Y, Wade R, Hyon SH, Ikada Y. Microspheres of biodegradable polymers as a drug delivery system in the vitreous. Invest Ophthalmol Vis Sci. 1991;32:1785–1790. [PubMed]
13. Smith TJ, Pearson PA, Blanford DL, Brown JD, Goins KA. Intravitreal sustained-release ganciclovir. Arch Ophthalmol. 1992;110:255–258. [PubMed]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists