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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

Sodium hydroxide solution, 49-51% in water, eluent for IC

Sigma-Aldrich

Glycerol solution, 83.5-89.5% (T)

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Sodium hydroxide solution, BioUltra, for molecular biology, 10 M in H₂O

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Potassium chloride, ≥99.99% trace metals basis

Sigma-Aldrich

3-Ethyl-2,4-pentanedione, mixture of tautomers, 98%

Supelco

(±)-α-Tocopherol, analytical standard

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Propylene glycol, ≥99.5% (GC), FCC, FG

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Potassium chloride, AnhydroBeads^™, −10 mesh, 99.99% trace metals basis

Sigma-Aldrich

Potassium chloride, AnhydroBeads^™, −10 mesh, 99.999% trace metals basis

Sigma-Aldrich

Sodium hydroxide, BioUltra, for luminescence, ≥98.0% (T), pellets

Supelco

Potassium chloride solution, for Ag/AgCl electrodes, ~3 M KCl, saturated with silver chloride

Supelco

Potassium chloride solution, conductance standard B acc. to ISO 7888, 0.01 M KCl

Supelco

ISA (ionic strength adjustment solution: 1 M KCl), 1 M KCl

Sigma-Aldrich

Potassium chloride, 99.999% trace metals basis

Sigma-Aldrich

Sodium phosphate dibasic solution, BioUltra, 0.5 M in H₂O

Supelco

Sodium hydroxide concentrate, 0.1 M NaOH in water (0.1N), Eluent concentrate for IC

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Boric acid-¹¹B, ≥99 atom % ¹¹B

Supelco

Phosphate Standard for IC, TraceCERT^®, 1000 mg/L phosphate in water (nominal concentration)

Sigma-Aldrich

Potassium chloride solution, 0.075 M, sterile-filtered, BioXtra, suitable for cell culture

Sigma-Aldrich

Potassium chloride, BioXtra, ≥99.0%

Sigma-Aldrich

Potassium chloride, for molecular biology, ≥99.0%

Sigma-Aldrich

Potassium chloride, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99.0%

Sigma-Aldrich

Sodium hydroxide, anhydrous, free-flowing, Redi-Dri^™, reagent grade, ≥98%, pellets

Sigma-Aldrich

(±)-α-Tocopherol, synthetic, ≥96% (HPLC)

Sigma-Aldrich

(±)-α-Tocopherol, tested according to Ph. Eur.

Supelco

Potassium chloride solution, conductance standard C acc. to ISO 7888, 0.001 M KCl