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AAPS PharmSciTech. 2005 March; 6(1): E1–E5.
Published online 2005 April 8. doi:  10.1208/pt060101
PMCID: PMC2750404

Oral formulation of a novel antiviral agent, PG301029, in a mixture of Gelucire 44/14 and DMA (2[ratio]1, wt/wt)


To develop an oral formulation for PG301029, a novel potent agent for the treatment of Hepatitis C virus infection, that not only has very low aqueous solubility but also degrades rapidly in water. The solubility of PG301029 was determined in water, various aqueous media, and several neat organic solvents. The stability of PG301029 was monitored at room temperature in buffess for 4 days, and in several neat organic solvents for up to 8 mo. Drug concentrations were measured by high-performance liquid chromatography (HPLC). Based on solubility and stability data, Gelucire 44/14 and DMA (N,N-dimethylacetamide) at a weight ratio of 2 to 1 were chosen as the formulation vehicle. After the vehicle was prepared, it was maintained in liquid form at ~40°C until the PG301029 was dissolved. The final formulation product was a semisolid at room temperature. The bioavailability of the formulation was tested on 4 female BALB/c mice. PG301029 is insoluble in all tested aqueous media, while its solubility is promising in DMA. This compound is unstable in aqueous media and some organic solvents; however, it is stable in DMA. This proposed formulation is able to hold up to 10 mg/mL of drug and is stable at 4°C. The shelf life for this formulation stored at 4°C is extrapolated to be greater than 4 years. This formulation dramatically increases the bioavailability of PG301029. This nonaqueous formulation solves the stability, solubility, and bioavailability problems for PG301029. This semisolid formulation can easily be incorporated into soft elastic capsules.

Keywords: PG301029, Gelucire 44/14, DMA (N,N-dimethylacetamide), oral formulation, HCV

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Camden J, inventor. The Proctor & Gamble Company, assignee. Viral treatment using thiourea or urea derivatives of aryl-thiadiazole. US patent WO0057869. October 10, 2000.
2. Physician's Desk Reference. 56th ed. Montvale, New Jersey: Medical Economics Company, Inc.; 2002. pp. 3153–3157.
3. Wong H, Jia L, Camden JB, Weitman SD. Liquid chromatographymass spectrometry assay of a thiadiazole derivative in mice: application to pharmacokinetic studies. J Chromatogr B Biomed Sci Appl. 2001;765:55–62. doi: 10.1016/S0378-4347(01)00403-0. [PubMed] [Cross Ref]
4. Jia L, Wong H, Cerna C, Weitman SD. Effect of nanonization on absorption of 30 1029:Ex Vivo andIn Vivo pharmacokinetic correlations determined by liquid chromatography/mass spectrometry. Pharm Res. 2002;19:1091–1096. doi: 10.1023/A:1019829622088. [PubMed] [Cross Ref]
5. Higuchi T, Connors KA. Phase-solubility techniques. In: Reilly C.N., editor. Advances in Analytical Chemistry and Instrumentation. New York: Interscience; 1965. pp. 117–212.
6. Kim S-N. Preclinical toxicology and pharmacology of dimethylacetamide, with clinical notes. Drug Metab Rev. 1988;19:345–368. doi: 10.3109/03602538808994140. [PubMed] [Cross Ref]
7. Inactive ingredient search for approved drug products. Available at: Accessed: December 5, 2004.
8. VUMON. (teniposide injection). Available at: cgi/generic2/teniposide.htm. Accessed: December 5, 2004.
9. Weiser AJ, Jackson LG, Carabasis RA, Mancall El, White JC. A phase I study of dimethylacetamide.Cancer Chemother Rep. 1962;16477–16485. [PubMed]
10. Amsidyl Injection. Available at: au/bhcv2/bhcmed.nsf/pages/pfcamsii/$File/pfcamsii.pdf. Accessed: December 5, 2004.
11. Gelucire 44/14 Prompt release and enhanced bioavailability. Bulletin Technique Gattefosse: Pharmaceutical Excipient for Oral Semi-Solid Formulations. 2001;3:4–4.
12. Shimpi S, Chauhan B, Mahadik KR, Paradkar A. Preparation and evaluation of diltiazem hydrochloride-Gelucire 43/01 floating granules prepared by melt granulation. AAPS PharmSciTech. 2004;5:E43–E43. doi: 10.1208/pt050343. [PMC free article] [PubMed] [Cross Ref]
13. Sheen PC, Kim EI, Petillo JJ, Serajuddin ATM. Bioavailability of a poorly water-soluble drug from tablet and solid dispersion in humans. J Pharm Sci. 1991;80:712–714. doi: 10.1002/jps.2600800722. [PubMed] [Cross Ref]
14. Pozzi F, Longo A, Lazzarini C, Carenzi A. Eur J Pharm Biopharm. 1991;37(4):243–6.
15. Aungst BJ, Nguyen N, Rogers NJ. Amphiphilic vehicles improve the oral bioavailability of a poorly soluble HIV protease inhibitor at high dose. Int J Pharm. 1997;156:79–88. doi: 10.1016/S0378-5173(97)00189-0. [Cross Ref]
16. Hauss DJ, Fogal SE, Ficorilli JV. Lipid-based delivery systems for improving the bioavailability and lymphatic transport of a poorly water-soluble LTB4 inhibitor. J Pharm Sci. 1998;87:164–169. doi: 10.1021/js970300n. [PubMed] [Cross Ref]
17. Serajuddin ATM. Poorly aqueous soluble drugs and surface-active solid dispersion carriers. Gattefosse Newletter: Formulink. 2002;7:1–4.

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