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

38364

Supelco

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

PHR1051

Supelco

Propylene glycol, Pharmaceutical Secondary Standard; Certified Reference Material

PHR1031

Supelco

Alpha Tocopherol, Pharmaceutical Secondary Standard; Certified Reference Material

60126

Sigma-Aldrich

Potassium chloride, tested according to Ph. Eur.

60128

Sigma-Aldrich

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

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

71687

Sigma-Aldrich

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

72068

Sigma-Aldrich

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

60134

Supelco

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

60137

Supelco

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

58221

Supelco

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

49781

Sigma-Aldrich

Glycerol solution, 83.5-89.5% (T)

72064

Supelco

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

60135

Supelco

Potassium chloride solution, BioUltra, ~3 M in H₂O

426148

Sigma-Aldrich

Boric acid-¹¹B, ≥99 atom % ¹¹B

409316

Sigma-Aldrich

Potassium chloride, 99.999% trace metals basis

451029

Sigma-Aldrich

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

47783

Supelco

(±)-α-Tocopherol, analytical standard

204099

Sigma-Aldrich

Potassium chloride, ≥99.99% trace metals basis

W294004

Sigma-Aldrich

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

449989

Sigma-Aldrich

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

P9333

Sigma-Aldrich

Potassium chloride, BioXtra, ≥99.0%

P9327

Sigma-Aldrich

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

P4347

Sigma-Aldrich

Propylene Glycol, meets USP testing specifications

T3251

Sigma-Aldrich

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

1576708

USP

Propylene glycol, United States Pharmacopeia (USP) Reference Standard

757527

Sigma-Aldrich

Sodium hydroxide, ultra dry, powder or crystals, 99.99% trace metals basis