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

901915

Sigma-Aldrich

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

60126

Sigma-Aldrich

Potassium chloride, tested according to Ph. Eur.

49781

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Glycerol solution, 83.5-89.5% (T)

204099

Sigma-Aldrich

Potassium chloride, ≥99.99% trace metals basis

47783

Supelco

(±)-α-Tocopherol, analytical standard

W294004

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

451029

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

449989

Sigma-Aldrich

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

71687

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

60137

Supelco

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

60136

Supelco

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

58221

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

409316

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Potassium chloride, 99.999% trace metals basis

94046

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Sodium phosphate dibasic solution, BioUltra, 0.5 M in H₂O

P9333

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P9541

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Potassium chloride, for molecular biology, ≥99.0%

P5405

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P9327

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

60138

Supelco

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

60128

Sigma-Aldrich

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

T3251

Sigma-Aldrich

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

P4347

Sigma-Aldrich

Propylene Glycol, meets USP testing specifications

90669

Sigma-Aldrich

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

PHR1051

Supelco

Propylene glycol, Pharmaceutical Secondary Standard; Certified Reference Material

PHR1031

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Alpha Tocopherol, Pharmaceutical Secondary Standard; Certified Reference Material

38364

Supelco

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

60134

Supelco

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

60142

Sigma-Aldrich

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

282979

Sigma-Aldrich

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

258024

Sigma-Aldrich

α-Tocopherol, ≥95.5%