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

T1550000

α-Tocopherol, European Pharmacopoeia (EP) Reference Standard

11607

Sigma-Aldrich

Boric acid, puriss., meets analytical specification of Ph. Eur., BP, NF, 99.5-100.5%, powder

71640

Sigma-Aldrich

Sodium phosphate dibasic, puriss. p.a., ACS reagent, anhydrous, ≥99.0% (T)

B0394

Sigma-Aldrich

Boric acid, ACS reagent, ≥99.5%

609765

Sigma-Aldrich

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

12-1120

Sigma-Aldrich

Glycerol, JIS special grade, ≥99.0%

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%

03-2910

Sigma-Aldrich

Boric acid, SAJ first grade, ≥99.5%

32900

Supelco

Benalaxyl-M, PESTANAL^®, analytical standard

T3634

Sigma-Aldrich

(+)-α-Tocopherol, from vegetable oil, Type V, ~1000 IU/g

82281

Sigma-Aldrich

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

B2645

Sigma-Aldrich

Boric acid, tablet, 1 g boric acid per tablet

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

16033

Sigma-Aldrich

1,2-Propanediol, meets analytical specification of Ph. Eur., BP, USP, ≥99.5%

N9007

Supelco

Noscapine hydrochloride hydrate, analytical standard

258024

Sigma-Aldrich

α-Tocopherol, ≥95.5%

1295607

USP

Glycerin, United States Pharmacopeia (USP) Reference Standard