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

258024

Sigma-Aldrich

α-Tocopherol, ≥95.5%

T3634

Sigma-Aldrich

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

B2645

Sigma-Aldrich

Boric acid, tablet, 1 g boric acid per tablet

N9007

Supelco

Noscapine hydrochloride hydrate, analytical standard

82281

Sigma-Aldrich

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

31146

Sigma-Aldrich

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

15523

Sigma-Aldrich

Glycerol, puriss., anhydrous, 99.0-101.0% (alkalimetric)

49770

Sigma-Aldrich

Glycerol, puriss. p.a., ACS reagent, anhydrous, dist., ≥99.5% (GC)

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

609765

Sigma-Aldrich

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

B0252

Sigma-Aldrich

Boric acid, ReagentPlus^®, ≥99.5%

11607

Sigma-Aldrich

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

RDD038

Sigma-Aldrich

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

71642

Sigma-Aldrich

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

S0876

Sigma-Aldrich

Sodium phosphate dibasic, ReagentPlus^®, ≥99.0%

S9763

Sigma-Aldrich

Sodium phosphate dibasic, ACS reagent, ≥99.0%

71636

Sigma-Aldrich

Sodium phosphate dibasic, BioUltra, Molecular Biology, ≥99.5% (T)

S5136

Sigma-Aldrich

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

S7907

Sigma-Aldrich

Sodium phosphate dibasic, BioXtra, ≥99.0%

S3264

Sigma-Aldrich

Sodium phosphate dibasic, Molecular Biology, ≥98.5% (titration)

71640

Sigma-Aldrich

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

255793

Sigma-Aldrich

Sodium phosphate dibasic, 99.95% trace metals basis

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)

G7757

Sigma-Aldrich

Glycerol, ReagentPlus^®, ≥99.0% (GC)

G6279

Sigma-Aldrich

Glycerol, BioXtra, ≥99% (GC)

G2025

Sigma-Aldrich

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

G9012

Sigma-Aldrich

Glycerol, ≥99.5%

W252506

Sigma-Aldrich

Glycerol, FCC, FG

G2289

Sigma-Aldrich

Glycerin, meets USP testing specifications