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

PMID24218989

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

43617

Supelco

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

94046

Sigma-Aldrich

Sodium phosphate dibasic solution, BioUltra, 0.5 M in H₂O

PHR1051

Supelco

Propylene glycol, Pharmaceutical Secondary Standard; Certified Reference Material

PHR1031

Supelco

Alpha Tocopherol, Pharmaceutical Secondary Standard; Certified Reference Material

38364

Supelco

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

60128

Sigma-Aldrich

Potassium chloride, BioUltra, for molecular biology, ≥99.5% (AT)

60126

Sigma-Aldrich

Potassium chloride, tested according to Ph. Eur.

90669

Sigma-Aldrich

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

49781

Sigma-Aldrich

Glycerol solution, 83.5-89.5% (T)

72068

Sigma-Aldrich

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

72064

Supelco

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

71687

Sigma-Aldrich

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

426148

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Boric acid-¹¹B, ≥99 atom % ¹¹B

451029

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

449989

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

W294004

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

282979

Sigma-Aldrich

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

60134

Supelco

Potassium chloride solution, conductance standard A acc. to ISO 7888, 0.1 M KCl

60136

Supelco

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

60138

Supelco

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

60142

Sigma-Aldrich

Potassium chloride solution, BioUltra, for molecular biology, ~1 M in H₂O

60135

Supelco

Potassium chloride solution, BioUltra, ~3 M in H₂O

58221

Supelco

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

60137

Supelco

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

47783

Supelco

(±)-α-Tocopherol, analytical standard

204099

Sigma-Aldrich

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409316

Sigma-Aldrich

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T3251

Sigma-Aldrich

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S2770

Sigma-Aldrich

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P4347

Sigma-Aldrich

Propylene Glycol, meets USP testing specifications