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

609765

Sigma-Aldrich

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

32900

Supelco

Benalaxyl-M, PESTANAL^®, analytical standard

258024

Sigma-Aldrich

α-Tocopherol, ≥95.5%

202878

Sigma-Aldrich

Boric acid, 99.999% trace metals basis

82281

Sigma-Aldrich

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

15663

Sigma-Aldrich

Boric acid, BioUltra, for molecular biology, ≥99.5% (T)

82280

Sigma-Aldrich

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

398039

Sigma-Aldrich

1,2-Propanediol, ACS reagent, ≥99.5%

12279

Supelco

1,2-Propanediol, analytical standard

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

N9007

Supelco

Noscapine hydrochloride hydrate, analytical standard

S7907

Sigma-Aldrich

Sodium phosphate dibasic, BioXtra, ≥99.0%

B6768

Sigma-Aldrich

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

B7660

Sigma-Aldrich

Boric acid, BioXtra, ≥99.5%

S0876

Sigma-Aldrich

Sodium phosphate dibasic, ReagentPlus^®, ≥99.0%

S5136

Sigma-Aldrich

Sodium phosphate dibasic, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99.0%

T1550000

α-Tocopherol, European Pharmacopoeia (EP) Reference Standard

RDD038

Sigma-Aldrich

Sodium phosphate dibasic, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99.0%, free-flowing, Redi-Dri^™

255793

Sigma-Aldrich

Sodium phosphate dibasic, 99.95% trace metals basis

31146

Sigma-Aldrich

Boric acid, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., buffer substance, ≥99.8%

71640

Sigma-Aldrich

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

11607

Sigma-Aldrich

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

B2645

Sigma-Aldrich

Boric acid, tablet, 1 g boric acid per tablet

71636

Sigma-Aldrich

Sodium phosphate dibasic, BioUltra, for molecular biology, ≥99.5% (T)

16033

Sigma-Aldrich

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

S3264

Sigma-Aldrich

Sodium phosphate dibasic, for molecular biology, ≥98.5% (titration)

B7901

Sigma-Aldrich

Boric acid, suitable for electrophoresis, ≥99.5%

04276

Sigma-Aldrich

Sodium phosphate dibasic, puriss., meets analytical specification of Ph. Eur., BP, USP, FCC, E 339, anhydrous, 98-100.5% (calc. to the dried substance)

B0252

Sigma-Aldrich

Boric acid, ReagentPlus^®, ≥99.5%

B0394

Sigma-Aldrich

Boric acid, ACS reagent, ≥99.5%