์ฝ˜ํ…์ธ ๋กœ ๊ฑด๋„ˆ๋›ฐ๊ธฐ
Merck

Formulation approaches to improving the delivery of an antiviral drug with activity against seasonal flu.

Pharmaceutical development and technology (2013-11-14)
Srinivasa M Sammeta, Li Wang, Shravan K Mutyam, Kathleen O'Loughlin, Carol E Green, Milton H Werner, Terence Kelly, Gita N Shankar
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The main objective of the present study was to develop formulations of noscapine hydrochloride hydrate with enhanced solubility and bioavailability using co-solvent- and cyclodextrin-based approaches. Different combinations of co-solvents, which were selected on the basis of high-throughput solubility screening, were subjected to in vitro intestinal drug permeability studies conducted with Ussing chambers. Vitamin E tocopherol polyethylene glycol succinate and propylene glycol based co-solvent formulations provided the maximum permeability coefficient for the drug. Inclusion complexes of the drug were prepared using hydroxypropyl-ฮฒ-cyclodextrin and sulphobutylether cyclodextrins. Pharmacokinetic studies were carried out in male Sprague-Dawley rats for the selected formulations. The relative bioavailabilities of the drug with the co-solvent- and cyclodextrin-based formulations were found to be similar.

MATERIALS
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Propylene glycol, European Pharmacopoeia (EP) Reference Standard
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Potassium chloride solution, conductance standard C acc. to ISO 7888, 0.001 M KCl
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(ยฑ)-ฮฑ-Tocopherol, tested according to Ph. Eur.
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(ยฑ)-ฮฑ-Tocopherol, analytical standard
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Alpha Tocopherol, Pharmaceutical Secondary Standard; Certified Reference Material
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(ยฑ)-ฮฑ-Tocopherol, synthetic, ≥96% (HPLC)
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Potassium chloride, ReagentPlusยฎ, โ‰ฅ99.0%
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Potassium chloride solution, BioUltra, ~3 M in H2O
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Potassium chloride solution, conductance standard B acc. to ISO 7888, 0.01 M KCl
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Phosphate Standard for IC, TraceCERTยฎ, 1000 mg/L phosphate in water (nominal concentration)
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Boric acid-11B, โ‰ฅ99 atom % 11B
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Sodium phosphate dibasic solution, BioUltra, 0.5 M in H2O
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Sodium hydroxide, BioXtra, ≥98% (acidimetric), pellets (anhydrous)
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Sodium hydroxide solution, 49-51% in water, eluent for IC
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Sodium hydroxide, puriss., meets analytical specification of Ph. Eur., BP, NF, E524, 98-100.5%, pellets
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Sodium hydroxide, reagent grade, 97%, flakes
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Glycerin, United States Pharmacopeia (USP) Reference Standard
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Sodium hydroxide, reagent grade, ≥98%, pellets (anhydrous)
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Sodium hydroxide, ACS reagent, ≥97.0%, pellets
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Propylene glycol, United States Pharmacopeia (USP) Reference Standard
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Propylene Glycol, meets USP testing specifications
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Sodium hydroxide, anhydrous, free-flowing, Redi-Driโ„ข, reagent grade, โ‰ฅ98%, pellets
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Sodium hydroxide solution, 1.0 N, BioReagent, suitable for cell culture