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

71640

Sigma-Aldrich

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

S9763

Sigma-Aldrich

Sodium phosphate dibasic, ACS reagent, ≥99.0%

202878

Sigma-Aldrich

Boric acid, 99.999% trace metals basis

G2025

Sigma-Aldrich

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

N9007

Supelco

Noscapine hydrochloride hydrate, analytical standard

G9012

Sigma-Aldrich

Glycerol, ≥99.5%

G2289

Sigma-Aldrich

Glycerin, meets USP testing specifications

G6279

Sigma-Aldrich

Glycerol, BioXtra, ≥99% (GC)

82280

Sigma-Aldrich

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

82281

Sigma-Aldrich

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

12279

Supelco

1,2-Propanediol, analytical standard

71642

Sigma-Aldrich

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

15663

Sigma-Aldrich

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

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%

49767

Sigma-Aldrich

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

49779

Sigma-Aldrich

Glycerol, tested according to Ph. Eur., anhydrous

PHR1020

Supelco

Glycerin, Pharmaceutical Secondary Standard; Certified Reference Material

1295607

USP

Glycerin, United States Pharmacopeia (USP) Reference Standard

G7757

Sigma-Aldrich

Glycerol, ReagentPlus^®, ≥99.0% (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

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%

RDD038

Sigma-Aldrich

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

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%

31146

Sigma-Aldrich

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

77067

Supelco

Glycerol, analytical standard