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

PHR1020

Supelco

Glycerin, Pharmaceutical Secondary Standard; Certified Reference Material

12-1130

Sigma-Aldrich

Glycerol, SAJ first grade, ≥98.0%

24-6180

Sigma-Aldrich

1,2-Propanediol, SAJ first grade, ≥99.0%

24-6170

Sigma-Aldrich

1,2-Propanediol, SAJ special grade, ≥99.0%

12-1120

Sigma-Aldrich

Glycerol, JIS special grade, ≥99.0%

03-2910

Sigma-Aldrich

Boric acid, SAJ first grade, ≥99.5%

T1550000

α-Tocopherol, European Pharmacopoeia (EP) Reference Standard

609765

Sigma-Aldrich

Sodium hydroxide-¹⁶O solution, 20 wt. % in H₂¹⁶O, 99.9 atom % ¹⁶O

134368

Sigma-Aldrich

1,2-Propanediol, ReagentPlus^®, 99%

W252506

Sigma-Aldrich

Glycerol, FCC, FG

258024

Sigma-Aldrich

α-Tocopherol, ≥95.5%

255793

Sigma-Aldrich

Sodium phosphate dibasic, 99.95% trace metals basis

32900

Supelco

Benalaxyl-M, PESTANAL^®, analytical standard

82281

Sigma-Aldrich

1,2-Propanediol, tested according to Ph. Eur.

71642

Sigma-Aldrich

Sodium phosphate dibasic, purum p.a., anhydrous, ≥98.0% (T)

49779

Sigma-Aldrich

Glycerol, tested according to Ph. Eur., anhydrous

49767

Sigma-Aldrich

Glycerol, BioUltra, for molecular biology, anhydrous, ≥99.5% (GC)

339067

Sigma-Aldrich

Boric acid, 99.97% trace metals basis

82280

Sigma-Aldrich

1,2-Propanediol, puriss. p.a., ACS reagent, ≥99.5% (GC)

398039

Sigma-Aldrich

1,2-Propanediol, ACS reagent, ≥99.5%

T1539

Sigma-Aldrich

(+)-α-Tocopherol, Type VI, from vegetable oil, liquid (≥0.88M based on potency, density and molecular wt.), BioReagent, suitable for insect cell culture, ≥1000 IU/g

S0876

Sigma-Aldrich

Sodium phosphate dibasic, ReagentPlus^®, ≥99.0%

B6768

Sigma-Aldrich

Boric acid, BioReagent, for molecular biology, suitable for cell culture, suitable for plant cell culture, ≥99.5%

B2645

Sigma-Aldrich

Boric acid, tablet, 1 g boric acid per tablet

G2025

Sigma-Aldrich

Glycerol, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for electrophoresis, ≥99% (GC)