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

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
ABSTRACT

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-β-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
Product Number
Brand
Product Description

Supelco
Alpha Tocopherol, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Propylene glycol, Pharmaceutical Secondary Standard; Certified Reference Material
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Phosphate Standard for IC, TraceCERT®, 1000 mg/L phosphate in water (nominal concentration)
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Sodium phosphate dibasic solution, BioUltra, 0.5 M in H2O
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Boric acid-11B, ≥99 atom % 11B
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(±)-α-Tocopherol, synthetic, ≥96% (HPLC)
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Propylene Glycol, meets USP testing specifications
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Propylene glycol, ≥99.5% (GC), FCC, FG
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(±)-α-Tocopherol, tested according to Ph. Eur.
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Potassium chloride solution, conductance standard A acc. to ISO 7888, 0.1 M KCl
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Potassium chloride solution, BioUltra, ~3 M in H2O
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Glycerol solution, 83.5-89.5% (T)
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3-Ethyl-2,4-pentanedione, mixture of tautomers, 98%
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Sodium hydroxide, puriss. p.a., ACS reagent, K ≤0.02%, ≥98.0% (T), pellets
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Potassium chloride, ACS reagent, 99.0-100.5%
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USP
Propylene glycol, United States Pharmacopeia (USP) Reference Standard
Propylene glycol, European Pharmacopoeia (EP) Reference Standard
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